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The purpose of this bibliography is to provide a brief survey of the literature covering the publication years 1997-1999. This bibliography includes citations from published articles, books, books chapters, and technical reports. Citations to articles in non-English languages are indicated with [ ] around the title. The language is also indicated. Citations are organized under subject categories; General, Adverse Effects, Mechanisms/Pharmacology, Therapeutic Use. Citations have been selected from the TOXLINE database of the National Library of Medicine, National Institutes of Health. The search strategy included terms for the general concept of herbals as well as many specifics.

Naturals, botanicals and minerals. Cosmet Toiletries 1998 Oct;113:81-2, 84, 86, 88, 90-1
IPA COPYRIGHT: ASHP A list of new natural, botanical, and mineral materials for the cosmetic industry, including trade names, properties, claims, applications, and sources, is presented.

Adamolekun B, Hakim JG. Opsoclonus-myoclonus associated with traditional medicine ingestion: case report. East Afr Med J 1998;75(2):120-1.
A case of Opsoclonus-Myoclonus occurring in a young man, in association with traditional herbal medicine consumption is presented. Clinical and laboratory investigations did not reveal any of the known aetiological associations of the Opsoclonus-Myoclonus syndrome, raising the possibility that the traditional herbal medicine may be aetiologically implicated. This report highlights the need for proper identification and documentation of the contents of common herbal remedies and their possible side effects amongst Africans.

Baek NI, Kim JM, Park JH, Ryu JH, Kim SI, et al . Ginsenoside Rs3, a genuine dammarane-glycoside from Korean red ginseng. Arch Pharmacal Res 1997;20(3):280-2.

Balcerska I, Wedzisz A, Uramowski J. [Nitrates and nitrites in selected herbs and herbal preparations]. Bromatol Chem Toksykol 1997;30(2):119-23. (Pol)
BIOSIS COPYRIGHT: BIOL ABS. Several single herbs, herbal blends and granulates were tested for their nitrate and nitrite content. Griess colorimetry was used. All test herbs and preparations were found to contain nitrates and nitrites.

Bao K. Traditional Chinese materia medica (TCMM). Altern Ther Health Med 1997;3(1):18.

Barton BE, Tagat JR. Current status of interleukin-6 inhibitors. Drugs Future 1997 Apr;22:391-5.
IPA COPYRIGHT: ASHP A review of interleukin inhibitors is presented, including biopharmaceuticals such as antibodies, toxic fusion proteins, and peptide antagonists; synthetic chemicals; and miscellaneous compounds such as botanical extracts, marine extract, and tretinoin (retinoic acid).

Borkowski B. [Herbal drugs used in atherosclerosis--antisclerotica]. Farm Pol 1998;54(10):435-47. (Pol)

Bull SS, Melian M. Contraception and culture: the use of yuyos in Paraguay. Health Care Women Int 1998;19(1):49-60.
The use of herbs (yuyos) as contraception is common practice in Paraguay. This report analyzes data from the 1995-1996 Paraguayan Reproductive Health Survey. The analysis reveals that women are more familiar with yuyos (88%) than any other method of family planning. Modeling the determinants of ever having relied on yuyos as contraception demonstrates that older women (OR = 1.043) and women with more children (OR = 2.283) are significantly more likely to have used yuyos, but an interaction between older women with more children shows they are less likely to have used this method (OR = .982). Women living in rural areas (OR = .664) and those with more education (OR = .883) are less likely to have used the method. These findings show widespread acceptance and use of yuyos for contraception in Paraguay. More research into the chemical properties of yuyos is needed to determine their contraceptive efficacy and to prevent harmful effects from their misuse.

Chan TY. Monitoring the safety of herbal medicines. Drug Saf 1997;17(4):209-15.
Extremely limited knowledge about the ingredients in herbal medicines and their effects in humans, the lack of stringent quality control and the heterogenous nature of herbal medicines all necessitate the continuous monitoring of the safety of these products. In Hong Kong, safety information on herbal medicines has come from the enquiries and reports received by our Drug and Poisons Information Service, on-going surveillance of patients treated in a large general teaching hospital and review of reports from the medical literature. Circumstances under which poisonings have occurred are also analysed in order to devise preventive measures. Once collected, this information is then distributed to health professionals in Hong Kong and abroad. WHO projects and pilot studies in Europe are also under way to promote and facilitate reporting of adverse reactions to herbal medicines.

Chandler F, Osborne F. Burdock. Can Pharm J 1997 Jun;130:46-9.
IPA COPYRIGHT: ASHP The botanical features, traditional and modern medicinal uses, constituents, pharmacology, toxicity, contraindications, precautions, and dosage of burdock (Arctium lappa; Arctium minus) are discussed.

Chavez ML, Chavez PI. Saint John's Wort. Hosp Pharm 1997 Dec;32:1621-8, 1631-2.
IPA COPYRIGHT: ASHP An overview of the chemistry, history, use, pharmacokinetics, and clinical pharmacology of St. John's Wort, a shrubby, perennial weed that has been used as an antidepressant, is presented, including a summary of clinical trials of St. John's Wort for depression as well as for antiviral effects, dosage and administration, and side effects and contraindications.

Chen DF, Zhang SX, Wang HK, Zhang SY, Sun QZ, Cosentino LM, Lee KH. Novel anti-HIV lancilactone C and related triterpenes from Kadsura lancilimba. J Nat Prod 1999;62(1):94-7.
Three new triterpene lactones, lancilactones A (1), B (2), and C (3), together with the known kadsulactone A (4), were isolated from the stems and roots of Kadsura lancilimba. Their structures and stereochemistries were determined primarily from mass and NMR spectral data. Compound 3 inhibited HIV replication with an EC50 value of 1.4 microg/mL and a therapeutic index of greater than 71.4.

Chung KT, Wong TY, Wei CI, Huang YW, Lin Y. Tannins and human health: a review. Crit Rev Food Sci Nutr 1998;38(6):421-64.
Tannins (commonly referred to as tannic acid) are water-soluble polyphenols that are present in many plant foods. They have been reported to be responsible for decreases in feed intake, growth rate, feed efficiency, net metabolizable energy, and protein digestibility in experimental animals. Therefore, foods rich in tannins are considered to be of low nutritional value. However, recent findings indicate that the major effect of tannins was not due to their inhibition on food consumption or digestion but rather the decreased efficiency in converting the absorbed nutrients to new body substances. Incidences of certain cancers, such as esophageal cancer, have been reported to be related to consumption of tannins-rich foods such as betel nuts and herbal teas, suggesting that tannins might be carcinogenic. However, other reports indicated that the carcinogenic activity of tannins might be related to components associated with tannins rather than tannins themselves. Interestingly, many reports indicated negative association between tea consumption and incidences of cancers. Tea polyphenols and many tannin components were suggested to be anticarcinogenic. Many tannin molecules have also been shown to reduce the mutagenic activity of a number of mutagens. Many carcinogens and/or mutagens produce oxygen-free radicals for interaction with cellular macromolecules. The anticarcinogenic and antimutagenic potentials of tannins may be related to their antioxidative property, which is important in protecting cellular oxidative damage, including lipid peroxidation. The generation of superoxide radicals was reported to be inhibited by tannins and related compounds. The antimicrobial activities of tannins are well documented. The growth of many fungi, yeasts, bacteria, and viruses was inhibited by tannins. We have also found that tannic acid and propyl gallate, but not gallic acid, were inhibitory to foodborne bacteria, aquatic bacteria, and off-flavor-producing microorganisms. Their antimicrobial properties seemed to be associated with the hydrolysis of ester linkage between gallic acid and polyols hydrolyzed after ripening of many edible fruits. Tannins in these fruits thus serve as a natural defense mechanism against microbial infections. The antimicrobial property of tannic acid can also be used in food processing to increase the shelf-life of certain foods, such as catfish fillets. Tannins have also been reported to exert other physiological effects, such as to accelerate blood clotting, reduce blood pressure, decrease the serum lipid level, produce liver necrosis, and modulate immunoresponses. The dosage and kind of tannins are critical to these effects. The aim of this review is to summarize and analyze the vast and sometimes conflicting literature on tannins and to provide as accurately as possible the needed information for assessment of the overall effects of tannins on human health.

Chyau CC, Mau JL. Release of volatile compounds from microwave heating of garlic juice with 2,4-decadienals. Food Chem 1999;64(4):531-5.
BIOSIS COPYRIGHT: BIOL ABS. Garlic (Allium sativum L.) juice and 2,4-decadienals were heated in a microwave oven at the full power of 700 W. The volatile compounds of heated samples were isolated using diethyl ether solvent extraction and analysed using gas chromatography and gas chromatography-mass spectrometry. A total of 23 compounds were identified from these samples, among which 14 sulfide compounds, five aldehydes, two alcohols, one acid and one furan were identified. Three tentatively identified compounds, dithio(1-propenyl)propionate, dihydro-2(3H)-thiophenthione and n-hexanethiol were newly found in deep-fried garlic flavor. During microwave heating, levels of most volatiles decreased as the heating time continued. 2-Pentylfuran, isopropyl alcohol, hexanal and (E)-2-octenal were formed from the degradation of 2,4-decadienals. Sulfur dioxide was generated predominantly from the degradation and oxidation of sulfide compounds.

Cicero LA, Pareddy SR, Rosenberg JM. Can depression patients be treated with worts? Drug Top 1997 Sep 1;141:24.
IPA COPYRIGHT: ASHP The use of Hypericum perforatum (St. John's Wort) for depression therapy, including results of studies, possible mechanisms of action, toxicity, and dosage, is presented.

Combest WL. Ginger. US Pharm 1998 Feb;23:74, 79, 83-4, 86.
IPA COPYRIGHT: ASHP An overview of the medicinal uses of Zingiber officinale (ginger) is presented, including a discussion of the chemical composition and active constituents of ginger, pharmacology, side effects, and toxicity.

Combest WL. Valerian. US Pharm 1997 Dec;22:62, 64, 66, 68.
IPA COPYRIGHT: ASHP The uses, chemical composition, active constituents, results of clinical studies, toxicity, dosage forms and recommendations of Valerian for insomnia are discussed.

Combest WL, Nemecz G. Echinacea. US Pharm 1997 Oct;22:126, 129-30, 132.
IPA COPYRIGHT: ASHP An overview of the medicinal uses of Echinacea species, which is also called purple coneflower, is presented, and components of active fractions of the plant, various types of Echinacea preparations, and the toxicity of Echinacea are considered.

Cornell S. Alternatives to hormone replacement therapy. Do they measure up to estrogen? Adv Nurse Pract 1997;5(7):45-6, 49, 72.

Crone CC, Wise TN. Use of herbal medicines among consultation-liaison populations. A review of current information regarding risks, interactions, and efficacy. Psychosomatics 1998;39(1):3-13. Consultation-liaison psychiatrists evaluate a wide variety of patients who are often disillusioned with conventional medical care and are seeking to gain some measure of control over their illness. With the growing popularity of alternative health care practices, consultation-liaison psychiatrists must learn more about the implications of herbal medicine usage. This review provides an overview of herbal medicines, a vital component of the alternative medicine movement.

Dasgupta P, Fowler CJ. Chillies: from antiquity to urology. Br J Urol 1997;80(6):845-52.

Davis WM. Most frequently asked questions regarding depression. Drug Top 1997 Oct 6;141:98-107.
IPA COPYRIGHT: ASHP Types of depression, risk factors, symptoms, causes, suicidal risk, genetic role, and therapy of clinical depression with antidepressants, including their side effects, effects on sex life, types of drugs used during pregnancy, herbal drugs, ethyl alcohol interactions, and electroconvulsive therapy, are discussed. This article qualifies for 2 hours U.S. CE credit by the ACPE.

De Smet PA. The role of plant-derived drugs and herbal medicines in healthcare. Drugs 1997;54(6):801-40.
Many of our present medicines are derived directly or indirectly from higher plants. While several classic plant drugs have lost much ground to synthetic competitors, others have gained a new investigational or therapeutical status in recent years. In addition, a number of novel plant-derived substances have entered into Western drug markets. Clinical plant-based research has made particularly rewarding progress in the important fields of anticancer (e.g. taxoids and camptothecins) and antimalarial (e.g. artemisinin compounds) therapies. In addition to purified plant-derived drugs, there is an enormous market for crude herbal medicines. Natural product research can often be guided by ethnopharmacological knowledge, and it can make substantial contributions to drug innovation by providing novel chemical structures and/or mechanisms of action. In the end, however, both plant-derived drugs and crude herbal medicines have to take the same pharmacoeconomic hurdle that has become important for new synthetic pharmaceuticals.

De Smet PA, Brouwers JR. Pharmacokinetic evaluation of herbal remedies. Basic introduction, applicability, current status and regulatory needs. Clin Pharmacokinet 1997;32(6):427-36.

De Vincenzi M, Mancini E. Monographs on botanical flavouring substances used in foods. Part VI. Fitoterapia 19997;68(1):49-61.
BIOSIS COPYRIGHT: BIOL ABS. RRM LITERATURE REVIEW ORIGANUM-MAJORANA ORIGANUM-CRETICUM MELITTIS-MELISSOPHYLLUM STACHYS-OFFICINALIS AJUGA-CHAMAEPITYS GALEOPSIS-SEGETUM POGOSTEMON-CABLIN VERBASCUM-DENSIFLORUM VERONICA-ALLIONII VERONICA-OFFICINALIS BALLOTA-NIGRA SALVIA-OFFICINALIS SATUREJA-MONTANA MARJORAM WOOD BETONY AJUGA PATCHOULI MULLEIN SPEEDWELL BLACK HOREHOUND SAGE WINTER SAVORY BIOCHEMISTRY AND BIOPHYSICS FOODS BOTANICAL FLAVORING SUBSTANCES CHEMICAL COMPONENTS TOXIC PROPERTIES.

Debrunner B, Meier B. Petasites hybridus: a tool for interdisciplinary research in phytotherapy. Pharm Acta Helv 1998;72(6):359-62.
The 3rd Petasites gathering took place in Romanshorn, Switzerland on March 29, 1996 and gave 16 European scientists the opportunity to transmit their latest considerable discoveries to interested researchers working in different scientific disciplines such as pharmacognosy, botany, chemistry, pharmacology, medicine or clinical pharmacy. The newest findings on Petasites hybridus as a significant plant drug showed very promising aspects of therapeutic utility. Great progress has been made in chemical analytical methods and the determination of pharmacological activities. Substantial advances have also occurred in the production of bioassay procedures and plant materials, particularly utilizing cell- and tissue-culture techniques.

Donaldson K. Introduction to the healing herbs. ORL Head Neck Nurs 1998;16(3):9-16.
For centuries, man has used plants for their healing properties. Today we refer to these plants as herbs. These plants play a principal part in all treatment modalities, both ancient and modern. The gentle, nourishing, and synergistic actions of herbal medicine make it an excellent treatment choice for all systems. Properties of ten commonly used herbs will be discussed. The herbs will be reviewed for their history, actions, indications and safety.

Duke CC, Moore DE, Roufogalis BD. St. John's wort. N Z Pharm 1998 Jan;18:13-4.
IPA COPYRIGHT: ASHP The characteristics, biological activity, common uses, clinical trials, and adverse effects of Hypericum perforatum (St. John's wort) are discussed.

Duncan MG. The effects of nutritional supplements on the treatment of depression, diabetes, and hypercholesterolemia in the renal patient. J Ren Nutr 1999;9(2):58-62.
The independent use of nutritional supplements has increased dramatically over the past several years. St. John's Wort for the treatment of depression, chromium for improvement of abnormal glucose and insulin regulation, and garlic for hypercholesterolemia, are among the more popular nutritional supplements being used by the population at large for their respective conditions. Depression, diabetes, and hypercholesterolemia are common to the renal patient. However, the efficacy of St. John's Wort, chromium, and garlic for these problems in the patient with impaired renal function is not known. This article reviews the pharmacology, efficacy, safety, and pharmokinetics of these three food supplements in the nonrenal patient. There are encouraging data suggesting successful treatment in the otherwise normal individual. However, clinical studies examining the safety of these three supplements for the treatment of depression, diabetes, and hypercholesterolemia in the patient with renal disease are lacking and preclude recommendation of their use.

Dunford A, Eldin S. Useful plants [letter; comment]. J R Soc Med 1997;90(3):178-9.

Eliason BC. Alternative medicine--the case of herbal remedies [letter]. N Engl J Med 1999;340(7):564; Discussion 566.

Eliason BC, Kruger J, Mark D, Rasmann DN. Dietary supplement users: demographics, product use, and medical system interaction. J Am Board Fam Pract 1997;10(4):265-71.
BACKGROUND: Dietary supplements-defined as vitamins and minerals, herbal products, tissue extracts, proteins and amino acids, and other products-are purchased to improve health and prevent disease. Little has been published, however, about the characteristics of either the products or the people who use them. METHODS: Consecutive customers visiting two health food stores during a 15-day period were interviewed by telephone. They were asked about their use of dietary supplements, demographics, and their use of the established health care system. RESULTS: Of the 194 customers contacted, 136 (70.1 percent) completed the survey. Respondents took a total of 805 supplements, most often to prevent a health problem (84.3 percent). Herbal products were most commonly used. Garlic, ginseng, and Ginkgo biloba were the herbs most frequently used. Fifty products were found to have previously reported toxicities, including vitamin A, which 9 customers were taking in megadoses. Most customers were white (94.1 percent), female (75.7 percent), had at least 1 year of college education (70.6 percent), had health insurance (95.6 percent), and had a regular physician (85.3 percent). CONCLUSION: Most of the dietary supplements consumed appear to be safe, but 50 of 805 had previously reported toxicities including megadoses of vitamin A. Garlic, ginseng, and Ginkgo biloba were the most commonly ingested herbs, and the medical literature supports their effectiveness for some conditions in humans. Customers of two health food stores had average to above-average education and took dietary supplements to stay healthy. They used the conventional health care system but did not typically consult their physician about dietary supplements. The pattern of use suggests that physicians might not be adequately addressing preventive and wellness issues in discussions with their patients. Furthermore, physicians might need to learn about dietary supplements so they can communicate with patients about them.

Etkin NL. Indigenous patterns of conserving biodiversity: pharmacologic implications. J Ethnopharmacol 1998;63(3):233-45.
The accelerating rate at which the world's botanical resources are being depleted today has inspired redoubled efforts on the part of global conservation programs. For the most part, this reflects the actions of outsiders who are culturally and politically detached from the threatened environments, and who identify species for conservation through western economic models. In view of this, ethnopharmacologists--and primarily those representing the social sciences--have drawn attention to the cogency of indigenous knowledge of biotic diversity and its conservation. This paper reviews how local paradigms of plant management promote conservation, and problematizes the issue specifically to the use of plants by Hausa peoples in northern Nigeria. The pharmacologic implications of indigenous patterns of plant use and conservation derive from the manifold and overlapping contexts in which plants, especially wild species, are used by local communities. These applications identify the importance of particular species and should be employed in assigning priority for the conservation of plants.

Falch B, Reichling J, Saller R. [Ginger: not only a spice. Investigation of effects and effectivity]. Dtsch Apoth Ztg 1997 Nov 20;137:47-52, 55-60.(Ger)
IPA COPYRIGHT: ASHP The occurrence, morphological, microscopical, and organoleptic characteristics, constituents, traditional and modern uses, pharmacological effects, clinical and toxicological investigations, dosages, and methods of the application of ginger (Zingiber officinale Roscoe) rhizome and its medical preparations are discussed.

Fisher E, Lacy E. Nutrition: nonvitamin food supplements. Pharm Times 1997 Nov;63:97-105.
IPA COPYRIGHT: ASHP An overview of nonvitamin food supplements is presented, including bee pollen, bioflavonoids, carnitine, chromium, ubidecarenone (coenzyme Q-10), ginseng, kelp, melatonin, and tryptophan; the problems associated with the studies performed on nonvitamin food supplements, the sources of claims made for them, potential problems with self-administration of nonvitamin food supplements by the patient, the possible adverse effects of such supplements, and the process of counseling patients on the relative merits of supplementing one's diet with these substances are also discussed. This article qualifies for 2 hours U.S. CE credit by the ACPE.

Gaedcke F. [St. John's Wort and its preparations: evaluation of quality with the aid of a selective reproducible HPLC procedure]. Dtsch Apoth Ztg 1997 Oct 16;137:117-21. (Ger)
IPA COPYRIGHT: ASHP The assessment of the pharmaceutical quality of the active principles of St. John's Wort (Hypericum perforatum), including hypericin and pseudohypericin, using a specially developed method with HPLC is discussed.

Germer S, Franz G. [Ginger: manifold medicinal crude drug. Uses and thin layer chromatographic (TLC) assay according to the German Pharmacopeia 1997]. Dtsch Apoth Ztg 1997 Nov 20;137:40-6. (Ger)
IPA COPYRIGHT: ASHP A discussion of the crude drug ginger (Zingiber officinale Roscoe) is presented, including historical and botanical aspects, cultivation and harvesting, processing the rhizome, potential adulteration, contents of active substances, and uses. Pharmacopeial methods of TLC analysis of the active ingredients in ginger extracts are included.

Gillespie SG. Herbal drugs and phytomedicinal agents. Pharm Times 1997 Dec;63:53-62.
IPA COPYRIGHT: ASHP An overview of herbal drugs and phytomedicinal agents is presented, including a discussion of the history of herbal medicine, an outline of the regulation of herbal drugs in the United States and Europe, the extent and the demographics of use of herbal drugs, the characteristics of herbal drugs regarding composition, standardization, and dosage forms, and the indications, contraindications, dose, and side effects of selected herbal drugs. This article qualifies for 2 hours U.S. CE credit by the ACPE.

Goldman LS. Use of herbal medicines among C-L populations [letter]. Psychosomatics 1998;39(5):482.

Goodyear K, Lewith G, Low JL. Randomized double-blind placebo-controlled trial of homoeopathic 'proving' for Belladonna C30. J R Soc Med 19998;91(11):579-82.
Homoeopathic drug pictures are developed by recording the symptomatic effects of homoeopathic remedies given to healthy volunteers (a 'proving'). In a double-blind randomized controlled trial we tested the hypothesis that individuals using an infinitesimal dilution of Belladonna (thirtieth potency, C30) would record more true symptoms, on a questionnaire that contained both true and false Belladonna proving symptoms, than those receiving placebo. 60 volunteers entered the study and 47 completed data collection. We were unable to distinguish between Belladonna C30 and placebo using our primary outcome measure. For the secondary outcome measure we analysed the number of individuals who proved to the remedy according to our predefined criteria: 4 out of 19 proved in the Belladonna C30 group and 1 out of 27 in the placebo group (difference not statistically significant). This pilot study does not demonstrate a clear proving reaction for Belladonna C30 versus placebo, but indicates how the question might be further investigated.

Gori M, Campbell RK. Natural products and diabetes treatment. Diabetes Educ 1998;24(2):201-2, 205-8.
Many natural products are promoted to improve the health status of patients with diabetes by people making a profit on these products. Few of these claims have any scientific basis. Certain natural products are potentially damaging to patients with chronic diseases, especially if the products are used instead of proven scientific treatment regimens. Many individuals believe that if a product is natural it must be effective and safe. What is ironic is that if the products were safe and effective, and if studies would have been done on humans to prove safety and effectiveness, the sales of the products would greatly increase (as opposed to present limited sales as herbs from health food stores). Some of the products do have a beneficial effect, especially as a placebo if the patient believes that the product is going to work. As can be seen from the summary of products that are listed here that claim to improve the treatment of patients with diabetes, very few are available in a standard form that would produce a known positive effect. The few products that do have a mild impact on lowering blood glucose levels are much less effective than standard treatments. In a recent review of the role of plant-derived drugs and herbal medicines in healthcare, no natural products were listed as having a beneficial effect on diabetes. Diabetes care providers need to confront the issue of the use of natural products with their patients. Patients should be taught the importance of using proven, effective treatment regimens. Any patient who decides to use a natural product should be followed closely to make sure that no toxic effects occur and that treatment objectives are achieved.

Grabarczyk H, Horoszkiewicz M, Bloszyk E. [Plant extracts in cosmetics]. Farm Pol 1997;53(6):250-7. (Pol)

Grauds C. At last--standardized botanical products. Pharm Times 1997 Apr;63:107.
IPA COPYRIGHT: ASHP The development of standardized botanical products is described, including the process of extraction of the plant material, how standards might be defined differently among competitive companies, and establishing therapeutic validity for standardized botanical products.

Grauds C. Herbal ephedra and the pharmacist. Pharm Times 1998 Mar;64:60, 62.
IPA COPYRIGHT: ASHP An overview of the popular herb ephedra (Ephedra species; Ma Huang), an herbal equivalent and precursor to the drugs ephedrine and pseudoephedrine, is presented, including the importance of pharmacists providing consultation to patients using this herb, indications for ephedra use, side effects, contraindications, and U.S. Food and Drug Administration (FDA) warnings and restrictions on ephedra-containing products.

Grauds C. Strong herb sellers: up-and-comers for 1998. Pharm Times 1998 May;64:48, 50.
IPA COPYRIGHT: ASHP The top 10 selling herbs as a result of a growing herbal market are listed, and research on the efficacy of Hypericum perforatum (St. John's wort) for depression and its potential drug interactions are briefly presented.

Gresser G. [Broom: medicinal and poisonous plant, plantation net and devil's broom]. Dtsch Apoth Ztg 1998 Mar 5;138:51-2, 55-9. (Ger)
IPA COPYRIGHT: ASHP An overview of the etymology, botanical characteristics, distribution range, active constituents, including biogenic amines, flavonoids and iso-flavonoids, along with the therapeutic uses and toxicity of the plant broom, Cytisus scoparius (L) LINK (Leguminose), is presented.

Grush LR, Nierenberg A, Keefe B, Cohen LS. St. John's Wort during pregnancy. JAMA 1998 Nov 11;280:1566.
IPA COPYRIGHT: ASHP The cases of 2 women, ages 38 and 43 yr, who took Hypericum perforatum (St. John's Wort) in preference to standard antidepressant therapy during pregnancy are reported; the first patient experienced a recurrence of major depression during her first trimester of pregnancy and initiated H. perforatum at 900 mg/day, and the second patient discontinued fluoxetine hydrochloride and methylphenidate hydrochloride, which had been prescribed for refractory depression, and substituted 900 mg/day of H. perforatum. In the first patient, pregnancy and labor were uneventful, and the infant had Apgar scores of 9 at 1 and 5 min. The patient discontinued H. perforatum and began breastfeeding. The baby developed jaundice on day 5, which required brief phototherapy. The patient resumed H. perforatum on day 20 at 300 mg/day, but continued breastfeeding. Examination of the baby at 4 and 33 days was within the normal range.

Halberstein RA. Traditional botanical remedies on a small Caribbean island: Middle (Grand) Caicos, West Indies. J Altern Complement Med 1997;3(3):227-39.
A descriptive survey of 18 medicinal plants utilized on Middle (Grand) Caicos Island in the West Indies revealed that each species has multiple applications. Phytochemical constituents, ascertained from published sources, suggest pharmacological/physiological efficacy in the ethnomedical treatment of various disorders. Traditional preparation procedures may enhance the chemotherapeutic value of the plant derivatives, while at the same time reducing their potential toxicity. The majority of species used in Middle Caicos are also exploited in other cultures but often for very different purposes.

Hammond GB, Fernandez ID, Villegas LF, Vaisberg AJ. A survey of traditional medicinal plants from the Callejon de Huaylas, Department of Ancash, Peru. J Ethnopharmacol 1998;61(1):17-30.
The medicinal uses of local flora from the Callejon de Huaylas, Department of Ancash, northeastern Peru, are reported. This geographical area has an old tradition of herbal healing. A total of 33 species have been documented through interactions with village elders, traditional doctors and herbalists. Of the 33 medicinal plant species surveyed in the Callejon de Huaylas, six have not been previously reported, seven have received only minor phytochemical coverage in the literature, and the medicinal uses of seven other plants have not been corroborated with traditional medicinal reports from around the world. The traditional medicinal uses of six medicinal plants have been corroborated with previously published reports but their biological activities have yet to be confirmed in the laboratory. The medicinal uses of four other plants have been corroborated with previously published reports and their biological activities have been confirmed in the laboratory. The purported medicinal use of three plant species could not be confirmed in the laboratory.

Harrison P. Herbal medicine takes root in Germany [see comments]. CMAJ 1998;158(5):637-9.
The sale of Herbal Medicine is a growth industry in Germany, where physicians routinely prescribe these products and annual sales have surpassed $ 2 billion. Pam Harrison says the rising popularity has been driven by German patients, who began demanding herbal alternatives to synthetic drugs. Medical schools responded by reintroducing lessons on a topic that had been phased out of the medical curriculum.

Havlick HD. From the customer's perspective. Natural Pharm 1998 Aug;2:1, 10-1.
IPA COPYRIGHT: ASHP The importance of pharmacists in keeping abreast of natural and herbal products in light of the fact that more consumers purchase their natural products from pharmacies rather than health food stores is discussed, including what consumers look for when purchasing an herbal product, and how pharmacists might better serve their customers and increase their customer base.

Heiligenstein E, Guenther G. Over-the-counter psychotropics: a review of melatonin, St John's wort, valerian, and kava-kava. J Am Coll Health 1998;46(6):271-6.
Use and availability of alternative healthcare products have revived in the last few years. The prevalence of supplement use in the United States is largely unknown but is thought to be widespread. In this article, four of the common substances used to treat emotional problems are reviewed. The plant or substance description, clinical indications, evidence of therapeutic efficacy, mechanisms of therapeutic actions, dosages and regimens, different commercially available preparations, and adverse effects and toxicities are described for melatonin, St John's wort, valerian, and kava-kava. That a product is "natural" does not mean that it is either safe or effective. Many supplements are potent drugs that lack sufficient data on safety, dose-response relationships, drug interactions, and purity.

Heinrich M, Ankli A, Frei B, Weimann C, Sticher O. Medicinal plants in Mexico: healers' consensus and cultural importance. Soc Sci Med 1998;47(11):1859-71.
Medicinal plants are an important element of indigenous medical systems in Mexico. These resources are usually regarded as part of a culture's traditional knowledge. This study examines the use of medicinal plants in four indigenous groups of Mexican Indians, Maya, Nahua, Zapotec and - for comparative purposes - Mixe. With the first three the methodology was similar, making a direct comparison of the results possible. In these studies, the relative importance of a medicinal plant within a culture is documented using a quantitative method. For the analysis the uses were grouped into 9-10 categories of indigenous uses. This report compares these data and uses the concept of informant consensus originally developed by Trotter and Logan for analysis. This indicates how homogenous the ethnobotanical information is. Generally the factor is high for gastrointestinal illnesses and for culture bound syndromes. While the species used by the 3 indigenous groups vary, the data indicate that there exist well-defined criteria specific for each culture which lead to the selection of a plant as a medicine. A large number of species are used for gastrointestinal illnesses by two or more of the indigenous groups. At least in this case, the multiple transfer of species and their uses within Mexico seems to be an important reason for the widespread use of a species. Medicinal plants in other categories (e.g. skin diseases) are usually known only in one culture and seem to be part of its traditional knowledge.

Heinrich M, Robles M, West JE, Ortiz De Montellano BR, Rodriguez E. Ethnopharmacology of Mexican asteraceae (Compositae). Annu Rev Pharmacol Toxicol 1998;38:539-65.
Traditional herbal remedies have increased in popularity in Europe and the United States in recent years but have always been important to people living in rural Mexico and to their Mexican American/Chicano descendants in the United States. Mexican American patients will often be ingesting herbal teas at the same time that they are being treated for their ailments with antibiotics or antiinflammatory agents. The plant family Asteraceae (Compositae) has contributed the largest number of plants to this pharmacopoeia; the reasons for the importance of this family include its large number of species in Mexico and its wide array of natural products that are useful in the treatment of the maladies that have afflicted the inhabitants of rural Mexico. These natural products include sesquiterpene lactones, polyacetylenes, alkaloids, monoterpenes, and various phenolics such as flavonoids. In this review, we emphasize the sesquiterpene lactones, a large group of compounds with antiinflammatory properties and the ability to relax smooth muscles and thereby relieve gastrointestinal distress. These compounds also readily form adducts with glutathione or free thiols and can thereby affect the metabolism, activity, and toxicology of a wide array of pharmacological agents.

Hendriks H. Pharmaceutical aspects of some Mentha herbs and their essential oils. Perfum Flavor 1998 Nov-Dec;23:15-23.
IPA COPYRIGHT: ASHP An overview of some herbs and essential oils of the Mentha species that are used in pharmaceuticals, including M. piperita (peppermint), peppermint oil, M. arvensis (cornmint; Japanese mint), cornmint oil, M. pulegium (pennyroyal), pennyroyal oil, M. spicata (spearmint), M. cardiaca (spearmint), and spearmint oil, is presented, including their quality control, formulations, therapeutic uses, adverse effects, and toxicity; menthol, a constituent of Mentha species essential oils, is mentioned.

Hippius H. St John's Wort (Hypericum perforatum)--a herbal antidepressant. Curr Med Res Opin 1998;14(3):171-84.
A number of clinical studies conducted over the past few years have indicated that whole extract of St John's wort (Hypericum perforatum L.) has antidepressant effects. The herbal antidepressant St John's wort offers promising results in the treatment of patients with mild and moderate depression (response rate of 60-70% estimated by analysis of pooled data). St John's wort preparations are well tolerated. Their use rarely leads to adverse drug reactions which, when they do occur, are mainly subjective symptoms (e.g. gastrointestinal, dizziness). The generally good tolerability of St John's wort preparations and the resulting high patient compliance in taking the prescribed medication, in conjunction with their efficacy in mild and moderate depression, make these preparations particularly suitable for use in outpatient practice. Tolerability is also very good in elderly patients. If a sufficiently high-dose course of treatment with St John's wort preparations (900 mg daily) does not lead to a clear improvement in depression after four to six weeks, therapy should be continued with an established ('classical') antidepressant.

Hu SY. Herbal teas and populace health care in tropical China. Am J Chin Med 1997;25(1):103-34.
Commercial Chinese herbal tea is the development of the populace in tropical and subtropical China consequential to their fight against infectious diseases and their struggle to explore local plants to relieve fever, to alleviate pain, to restore strength and to modulate immunity against viral epidemics. From these ethnomedical experiences, two types of herbal teas were commercialized, namely, liangcha and medicated teas. Liangcha refers to a ready-made decoction infused from wild plants served in simple stores in cities and towns. Medicated teas are parcelled material prepared from crude drugs with or without tea (Camellia sinensis [L.] O. Ktze,), sold in colorful boxes and bags to people for use at home. Investigations of liangcha were made in Hong Kong and Macao, and studies for medicated teas were done from samples obtained in Chinese stores at Boston. A total of 127 source species of these herbal teas were identified and arranged in two alphabetical lists by the botanical names, each followed by an English common name in parenthesis, part used, frequency in samples, and family. External recognizing characters of medicated teas, discussions of problems encountered in identifying source species, relevant toxicities, and potential new vegetal pharmaceutical resources are given.

Huxtable RJ. Safety of botanicals: historical perspective [editorial]. Proc West Pharmacol Soc 1998;41:1-10.

Iorio L, Nacca RG, Simonelli R. Cistercian medicinal herbs for renal therapy in the 15th century. Am J Nephrol 1997;17(3-4):286-8.
The rule conceived the monastery as a citadel of divine service so that medicine, together with other arts, was the subject of studies and searches which contributed to the foundation of monastic medicine. In the 14th and 15th centuries, Cistercian monks did not limit themselves to the study of the ancient treatises on medicinal herbs, but enlarged their knowledge through clinical experience to such an extent that they created the principal therapy of diseases for about five centuries.

Jambor J. [Strategies for the development of herbal drugs market]. Farm Pol 19998;54(5):201-9. (Pol)

Johnson ST, Wordell CJ. Homeopathic and herbal medicine: considerations for formulary evaluation. Formulary 1997 Nov;32:1166-8, 1171-3.
IPA COPYRIGHT: ASHP The principles, efficacy, risks, regulation, and examples of homeopathy and herbal medicine therapy, and formulary considerations for these types of alternative medicine are discussed.

Keplinger K, Laus G, Wurm M, Dierich MP, Teppner H. Uncaria tomentosa (Willd.) DC.--ethnomedicinal use and new pharmacological, toxicological and botanical results. J Ethnopharmacol 1999;64(1):23-34.
The medicinal system of the Ashaninka Indians in Peru is portrayed. Three categories of medical disorders and healers are recognized. A human is viewed to consist of a physical and a spiritual being who communicate with each other by means of a regulating element. The significance of Uncaria tomentosa (Willd.) DC. (Rubiaceae), locally known as una de gato, in traditional medicine is emphasized by its exclusive use by priests to influence this regulation. Pharmacological and toxicological results obtained with extracts or isolated compounds are summarized. Pentacyclic oxindole alkaloids stimulate endothelial cells in vitro to produce a lymphocyte-proliferation-regulating factor. Tetracyclic oxindole alkaloids act as antagonists. A significant normalization of lymphocyte percentage was observed in vivo although total leucocyte numbers did not change.

Khaliq Y. Alternative medicine: what pharmacists need to know. Pharm Pract 1997 Mar;13:44-50, 83-5.
IPA COPYRIGHT: ASHP An overview of alternative medicine with a focus on herbal medicine, homeopathy, and vitamin therapy is presented; the attitudes of patients, physicians, and pharmacists, benefits of alternative medicine, disadvantages of these therapies, such as lack of evidence, toxicity, drug interactions, and lack of regulation and quality control, and the pharmacist's role are discussed.

Klepser TB, Klepser ME. Unsafe and potentially safe herbal therapies. Am J Health Syst Pharm 1999;56(2):125-38; Quiz 139-41.
Unsafe and potentially safe herbal therapies are discussed. The use of herbal therapies is on the rise in the United States, but most pharmacists are not adequately prepared educationally to meet patients' requests for information on herbal products. Pharmacists must also cope with an environment in which there is relatively little regulation of herbal therapies by FDA. Many herbs have been identified as unsafe, including borage, calamus, coltsfoot, comfrey, life root, sassafras, chaparral, germander, licorice, and ma huang. Potentially safe herbs include feverfew, garlic, ginkgo, Asian ginseng, saw palmetto, St. John's wort, and valerian. Clinical trials have been used to evaluate feverfew for migraine prevention and rheumatoid arthritis; garlic for hypertension, hyperlipidemia, and infections; ginkgo for circulatory disturbances and dementia; ginseng for fatigue and cancer prevention; and saw palmetto for benign prostatic hyperplasia. Also studied in formal trials have been St. John's wort for depression and valerian for insomnia. The clinical trial results are suggestive of efficacy of some herbal therapies for some conditions. German Commission E, a regulatory body that evaluates the safety and efficacy of herbs on the basis of clinical trials, cases, and other scientific literature, has established indications and dosage recommendations for many herbal therapies. Pharmacists have a responsibility to educate themselves about herbal therapies in order to help patients discern the facts from the fiction, avoid harm, and gain what benefits may be available.

Kligler B. Herbal medicines and the family physician [editorial; comment]. Am Fam Physician 1998;58(5):1064-5.

Klink B. Alternative medicines: is natural really better? Drug Top 1997 Jun 2;141:99, 103.
IPA COPYRIGHT: ASHP The rapid sales growth and risks vs benefits of alternative medicine and herbal products and the role of the pharmacists who sell these products are discussed.

Kosalec I. [History and future of Echinacea species--natural immunostimulating plants]. Farm Glas 1998 May;54:161-70. (Scr)

Kozyrskyj A. Herbal products in Canada. How safe are they? [see comments]. Can Fam Physician 1997;43:697-702.
OBJECTIVE: To examine existing evidence and inform family physicians about issues concerning herbal product use in Canada. QUALITY OF EVIDENCE: The Canadian Food and Drug Act and findings of an Expert Advisory Committee on Herbs and Botanical Preparations were consulted to provide an overview of the issues regarding herbal product regulation in Canada. Case reports of herbal toxicity were identified to illustrate some of the hazards of herbal products, and references provided to guide health professional in searching the literature for clinical trials that evaluate these drugs' efficacy. MAIN FINDINGS: Herbal products not registered as drugs in Canada are sold as foods and are exempt from the drug review process that evaluates product efficacy and safety. This places the public at risk of unwanted effects from the use of herbal products that are adulterated with other substances and of forgoing effective conventional therapy. Moreover, consumers are exposed to a plethora of information portraying herbal products as harmless. Some progress has been made to address these concerns by facilitating the registration of herbal products as drugs. CONCLUSIONS: Most herbal products that were evaluated were unsafe or ineffective, or no information was available to evaluate their efficacy. Despite the perception that herbal products are innocuous, family physicians need to be aware that herbal therapy can be harmful in order to help their patients make informed choices.

Krishnaswamy K, Raghuramulu N. Bioactive phytochemicals with emphasis on dietary practices. Indian J Med Res 1998;108:167-81.
Diet can modify the pathophysiological processes of various metabolic disorders and can be an effective preventive strategy for various disease processes most of which are known to involve oxidative damage. Both nutrient and non-nutrient components of the diet have been recognized for their anti-oxidant and other potential benefits. Plant foods contain phytochemicals such as flavonoids, phenolic acids, etc., which show biological activity. Some common foods used in Indian culinary practices were assessed for their anti-oxidant, anti-mutagenic and anti-carcinogenic effects and vitamin D activity and evaluated for their plausible biological effects. Green leafy vegetables had the highest anti-oxidant activity followed by wheat and rice. Cooking decreased this activity. Eugenol, the active principle of clove, was shown to offer protection against CCl4 induced hepatotoxicity in rats. It also showed anti-peroxidative activity in addition to decrease in O2 formation. Studies on the anti-carcinogenic effect of turmeric/curcumin revealed that both are potent anti-mutagens in vivo and reduce the adducted DNA levels in liver of rates challenged with B(a)P. In another study, Syrian hamsters receiving turmeric/curcumin through diet or local paint on cheek pouch had lower tumour burden as well as adducted DNA level against 7-12-DMBA challenge. Turmeric/curcumin were found to be better anti-tumour agents when given in the post initiation phase of carcinogenesis. The beneficial effect of turmeric was found to be due to its anti-oxidant potential. Studies on humans at risk of palatal cancer due to reverse smoking showed that turmeric (1 g/day) for 9 months had a significant impact on the regression of precancerous lesions. Onion and garlic also possess anti-mutagenic principle. Further studies on the bioactive phytochemicals in plants showed that certain plants belonging to Solanaceae (Cestrum diurnum, Lycopersicon esculentum and Solanum melongena) have calcinogenic potential and vitamin D like activity. In view of the vast data on bioactive principles from plants, it is suggested that dietary prevention coupled with other life-style changes in perhaps the right answer for prevention of cancer and other chronic diseases in India.

Kumar M, Berwal JS. Sensitivity of food pathogens to garlic (Allium sativum). J Appl Microbiol 1998;84(2):213-5.
The inhibitory activity of garlic (Allium sativum) against Staphylococcus aureus, Salmonella typhi, Escherichia coli and Listeria monocytogenes was measured by the 'turbidity' method. Minimum inhibitory concentration (MIC) of garlic at 80% inhibition level was calculated for these bacteria. All bacterial pathogenic strains tested were inhibited by garlic; E. coli was most sensitive and Listeria monocytogenes was least sensitive. Therefore, garlic has potential for the preservation of processed foods.

La Valle JB. St. John's Wort: there's no magic bullet. Drug Store News Chain Pharm 1998 Jan;8:15.
IPA COPYRIGHT: ASHP The problems associated with the consumer rush to take St. John's Wort (Hypericum perforatum) for depression are discussed, including problems with self-diagnosis and treatment of depression, subtherapeutic dosing of the compound, drug interactions with monoamine oxidase (MAO) inhibitors or other antidepressants, side effects, and methods for discontinuation of traditional antidepressants.

Lavalle J. Ginseng: ancient Chinese cure-all. Drug Store News For Pharm 1997 Feb;7:42.
IPA COPYRIGHT: ASHP The pharmacology, action, indications, toxicities, contraindications, and dosage of ginseng are presented.

Lazarowych NJ, Pekos P. Use of fingerprinting and marker compounds for identification and standardization of botanical drugs: strategies for applying pharmaceutical HPLC analysis to herbal products. Drug Inf J 1998;32(2):497-512.
IPA COPYRIGHT: ASHP The use of HPLC fingerprinting and markers to identify herbal drug materials, set specifications for raw materials, and standardize botanical preparations during manufacturing is discussed; the method was illustrated using Valeriana officinalis (valerian) and Tanacetum parthenium (feverfew).

Lee OS, Kang HH, Han SH. Oriental herbs in cosmetics. Cosmet Toiletries 1997 Jan;112:57-64.
IPA COPYRIGHT: ASHP The use of plant extracts as cosmetic ingredients is presented, including ginseng from Panax ginseng and Swertia for anti-aging preparations, Angelica, Glycyrrhiza (licorice), Lithospermum, and Scutellaria roots as anti-inflammatory agents, Houttuynia, Phellodendron, and Sophora as antimicrobials, Lonicera and Sanguisorba as astringents, Angelica dahurica, Angelica korea, Bupleurum, and Cnidium rhizome as anti-tyrosinase actives, teas as free-radical scavengers, Angelica keiskei, Coptis, and Lonicera as ultraviolet protectants, Morus lhou (mulberry) for skin whitening, and other agents for hair growth and care.

Lepik K. Safety of herbal medications in pregnancy. Can Pharm J 1997 Apr;130:29-33.
IPA COPYRIGHT: ASHP A summary of safety information that is relevant to the use of selected herbal medications during pregnancy is presented, including pharmacologic, toxicologic, and reproductive effects of 26 herbal remedies.

Li Y, Wu YL. How Chinese scientists discovered qinghaosu (artemisinin) and developed its derivatives? What are the future perspectives? Med Trop (Mars) 1998;58(3 Suppl):9-12.
Since the middle of this century and especially since the 1960s and 1970s. Chinese scientists have put considerable effort and resources into the search for new antimalarial compounds extracted from Chinese traditional herbs. Archaeological findings indicate that qinghao (Artemisia annua L.) has been used as a traditional remedy in China for over two thousand years. Its antimalarial principle was finally isolated in 1971 and named artemisinin or qinghaosu (meaning the principle of qinghao in Chinese). Its rapid action, low toxicity and powerful effect against falciparum malaria made it a favored subject for research. In 1976, the unique structure of the molecule, characterized by an endoperoxide and an alternative O-C-O-C segment, was identified. The specific lactone reduction discovered during the determination of the structure opened the way for the synthesis of qinghaosu derivatives, and thereafter a series of more active and more oil- or water-soluble derivatives was developed. Subsequent studies of the structure/activity relationship led to the discovery of dihydroartemisinin, artemether and artesunate. Now qinghaosu and these three derivatives are being used around the world as effective new antimalarial drugs in the fight against falciparum malaria, including multi-drug-resistant Plasmodium falciparum. At the present time new qinghaosu analogues or derivatives are being developed and studies of their structure/activity relationships, their antimalarial mechanisms, their interaction with ferrous ions and the DNA damage associated with these processes are being actively pursued. In addition, recent studies also indicate that some qinghaosu derivatives have other bioactivities, including antiparasitic (against Schistosoma japonicum, Toxoplasma gondii and so on) and anticancer activities. Research into qinghaosu and its derivatives has already produced and will no doubt continue to produce results of the utmost importance in the fight against malaria and other diseases.

Locock RA. Herbal medicine: Essiac. Can Pharm J 1997 Feb;130:18-9, 51.
IPA COPYRIGHT: ASHP The actions and uses of the herbal preparation, Essiac, and its constituents, including Arctium lappa L. (burdock root), Rumex acetosella L. (sheep sorrel herb), Ulmus fulva Michaux (slippery elm bark), Rheum palmatum L. (turkey rhubarb root), Nasturtium officinale (Rorippa nasturtium; watercress), Laminariales species (kelp), Cnicus (blessed thistle), and Trifolium pratense L. (red clover), are presented.

Mamedov NA, Craker LE. Herbs and plant systematics. J Herbs Spices Med Plants 1997;5(2):1-2.
IPA COPYRIGHT: ASHP The methodology of plant systematics and the importance of using systematics in the search for new medicinal and aromatic plant materials are discussed.

Manandhar NP. Native phytotherapy among the Raute tribes of Dadeldhura district, Nepal. J Ethnopharmacol 1998;60(3):199-206.
The herbal drugs used by the Raute tribe of far-western Nepal are discussed. A total of 47 species of plants including one species of pteridophyte, four monocotyledons and 42 dicotyledons, and 17 types of diseases treated, have been identified from this study. Medicinal uses of 15 species (31%) are unrecorded from other parts of the country.

Masood E. 'Medicinal plants threatened by over-use' [news] [see comments]. Nature 1997;385(6617):570.

McIntyre RV. Herbal healers [editorial]. J Okla State Med Assoc 1998;91(5):271.

McKinney DE. Saw palmetto for benign prostatic hyperplasia. JAMA 1999 May 12;281:1699.
IPA COPYRIGHT: ASHP A physician's viewpoints regarding the quality of medicinal plant products, particularly extracts of saw palmetto (Serenoa repens) for benign prostatic hypertrophy (BPH) are presented, including 4 major points to consider when evaluating a manufacturer's products for patients. Other plant products that may also have value in the treatment of BPH were briefly discussed.

McLaughlin JL, Rogers LL, Anderson JE. Use of biological assays to evaluate botanicals. Drug Inf J 1998;32(2):513-24.
IPA COPYRIGHT: ASHP The materials and procedures for 4 bioassays used to screen and direct the fractionation of botanical extracts in drug discovery are described, and the application of the methods in the discovery of Annonaceous acetogenins is discussed.

Menke J. Herbal remedies. S D J Med 1997;50(6):207-8.

Milliken W. Malaria and antimalarial plants in Roraima, Brazil. Trop Doct 1997;27(Suppl 1):20-5.
One of the numerous problems created by the gold rush which took place in northern Brazil (Roraima State) at the end of the 1980s was a severe epidemic of malaria amongst the indigenous peoples of the region. Worst hit were the Yanomami Indians, who had lived in almost total isolation prior to this event. The problem has been exacerbated by the development of chloroquine-resistant strains of Plasmodium falciparum. In an effort to identify viable alternatives to dependence on western medicine for malaria treatment, a survey was carried out on the local plant species (wild and cultivated) used for this purpose in Roraima. Fieldwork was carried out amongst seven indigenous peoples, as well as with the non-indigenous settlers. Over 90 species were collected, many of which have been cited as used for treatment of malaria and fevers elsewhere. Knowledge of antimalarial plants was found to vary greatly between the communities, and in some cases there was evidence of recent experimentation. Initial screening of plant extracts has shown a high incidence of significant antimalarial activity amongst the species collected.

Montbriand MJ. Past and present herbs used to treat cancer: medicine, magic, or poison? Oncol Nurs Forum 1999;26(1):49-60.
PURPOSE/OBJECTIVES: To provide an overview of the past and present use of herbs, thereby dispelling the belief that herbs are secret cancer remedies unknown to or ignored by the biomedical community. DATA SOURCES: Historical and current pharmacy, medical, and nursing literature. DATA SYNTHESIS: More than 3,000 species of herbs used in treating cancer since 2838 BC are known to biomedicine, yet popular lay literature persists in perpetrating the myth that medicine has ignored the potential uses of herbs. Secrecy about herbs has been fashionable since the Middle Ages. Magical and virtuous herbs, named in a book of secrets from that age, are examined for their historical and current use in cancer treatment. Popular unproven herbs, as well as proven herbs used in chemotherapy, also are discussed. CONCLUSIONS: Greater accessibility to information about the use of herbs historically, popularly, and currently would help dispel the secrecy, giving healthcare professionals and patients and opportunity to make informed choices. IMPLICATIONS FOR NURSING PRACTICE: Nurses with knowledge of herbs can be valuable resources to patients and professional colleagues. Members of the professional community (nurses, doctors, pharmacists, and social workers) need to take collegial responsibility in informing each other and their patients about herbs, including their potential risks, possible benefits, and antidotes for overdose.

Muller JL, Clauson KA. Top herbal products encountered in drug information requests. Part 2. Drug Ben Trends 1998 Jun;10:21-3.
IPA COPYRIGHT: ASHP An overview of the indications, dosage, side effects, possible drug interactions, and clinical studies of 2 top selling herbal products, Hypericum perforatum (St. John's Wort) and Serenoa repens (saw palmetto), is presented.

Myerscough M. Herbal remedies. How much do you know? Aust Fam Physician 1998;27(11):1037-40.
In this article the importance of knowledge about herbal remedies in general practice is discussed using guarana (Paullinia cupana), St John's wort (Hypericum perforatum), and gingko (Ginkgo biloba) as examples. Obtaining information about herbal remedies can be difficult. Lack of clinical data about the use, safety, efficacy and general practitioner attitudes to herbal remedies creates research opportunities in this area of general practice.

Nemecz G. Chamomile. US Pharm 1998 Mar;23:104, 110, 112, 115-6.
IPA COPYRIGHT: ASHP The therapeutic uses of chamomile, including antiphlogistic, spasmolytic, sedative, hypnotic, analgesic, and antimicrobial effects as well as its chemical composition, pharmacological action, toxicity, and dosage, are presented.

Nemecz G. Saw palmetto. US Pharm 1998 Jan;23:97-8, 100, 102.
IPA COPYRIGHT: ASHP The history, chemical composition, medicinal uses, and adverse effects of Serenoa repens (saw palmetto) are discussed.

Nemecz G, Combest WL. Feverfew. US Pharm 1997 Nov;22:122, 124, 126, 128.
IPA COPYRIGHT: ASHP An overview of the chemical composition and pharmacological effects of feverfew (Tanacetum parthenium), a perennial herb that has shown efficacy in the treatment of migraine headaches, is presented, including a summary of clinical studies of feverfew in the treatment of migraine headaches and arthritis, its anti-inflammatory effects, its effects on platelet aggregation and vascular smooth muscle contraction, its toxicity and adverse effects, and dosage forms and recommended use.

Neuwinger HD, Mebs D. [Boophone disticha: hallucinogenic African plant]. Dtsch Apoth Ztg 1997 Apr 3;137:51-6. (Ger)
IPA COPYRIGHT: ASHP An overview of the botanical characteristics, uses in African folk medicine, chemistry, toxicology, and pharmacology of the hallucinogenic contents of the plant Boophone disticha (L) Herbert (Amaryllidaceae) is presented.

Norton SA. Herbal medicines in Hawaii from tradition to convention. Hawaii Med J 1998;57(1):382-6.
The stories of kava and chaulmoogra demonstrate the importance of herbal products in ancient and recent Hawaiian medicine. Kava is a psychoactive beverage that has been used ceremonially for millennia throughout the Pacific. It is a nonfermented depressant that causes tranquil intoxication in which thoughts and memory remain clear. Its broad pharmacologic activity led to use in Hawaii to treat skin disorders and later in Germany to treat gonorrhea. Kava is now available outside the Pacific basin as a relaxant, emerging as a popular, albeit deritualized, natural product. In the late 19th century, the main treatment for leprosy was chaulmoogra, extracted from Hydnocarpus seeds. Chaulmoogra had been a traditional treatment for skin diseases in Ayurvedic and Chinese medicine. Chaulmoogra from Asian markets was expensive and usually adulterated so the USDA decided to plant Hydnocarpus in Hawaii. Joseph Rock, a botanist at University of Hawaii, trekked through southeast Asia collecting fresh seeds to plant on Oahu. Rock's trees provided chaulmoogra for leprosy patients on Molokai and elsewhere until it was replaced by dapsone. Chaulmoogra, once the treatment for leprosy worldwide, is now nearly forgotten; kava, once poorly known outside the Pacific, is now a widely-used alternative medicine. Hawaii will probably continue its role in the transition of plants from traditional use to conventional use.

Nwosu MO. Aspects of ethnobotanical medicine in southeast Nigeria. J Altern Complement Med 1998;4(3):305-10.
OBJECTIVE: To document the diversity and traditional use of tropical plants as medicine by the indigenous people of southeast Nigeria. DESIGN: Information was obtained by interviews conducted with the aid of questionnaires and facilitators during field surveys carried out from January 1993 to June 1994. Voucher herbarium specimens were identified at the University of Nigeria, Nsukka Herbarium, in collaboration with Bernhard Zepernick (former Curator), Botanisches Museum, Berlin. Specimens were photographed. RESULTS: Data are summarized in the form of a table, summarizing the plants commonly used by the traditional doctors or medicine men. Herbal preparations are arranged alphabetically under family and species. The data are presented in the order: botanical name, collection number, vernacular name, locality, plant habit/status, and reported medicinal applications.

O'Hara M, Kiefer D, Farrell K, Kemper K. A review of 12 commonly used medicinal herbs. Arch Fam Med 1998;7(6):523-36.
A large and increasing number of patients use medicinal herbs or seek the advice of their physician regarding their use. More than one third of Americans use herbs for health purposes, yet patients (and physicians) often lack accurate information about the safety and efficacy of herbal remedies. Burgeoning interest in medicinal herbs has increased scientific scrutiny of their therapeutic potential and safety, thereby providing physicians with data to help patients make wise decisions about their use. This article provides a review of the data on 12 of the most commonly used herbs in the United States. In addition, we provide practical information and guidelines for the judicious use of medicinal herbs.

Palsson K, Jaenson TG. Plant products used as mosquito repellents in Guinea Bissau, West Africa. Acta Trop 1999;72(1):39-52.
By standardized interviews of people in 23 rural villages, in the Oio region of Guinea Bissau, we collected data on which plant species and plant derived products or methods people use to reduce mosquito biting activity.The following plants were used to reduce numbers of mosquitoes indoors at night: fresh or smouldering Hyptis suaveolens Poit. (Lamiaceae), smoke of the bark of Daniellia oliveri Rolfe (Caesalpiniaceae), smoke of the infructescence of Elaeis guineensis Jacq. (Arecaceae), smoke of the seed capsules of Parkia biglobosa (Jacq.) Benth. (Mimosaceae), smoke of the leaves of Azadirachta indica A.Juss. (Meliaceae) and Eucalyptus sp. (Myrtaceae), fresh Ocimum canum Sims (Lamiaceae), and fresh Senna occidentalis (L.) Link (Caesalpiniaceae). In two field experiments we estimated the 'repellent activity' of certain of these plants and compared their efficacies with those of two commercially available mosquito repellents, i.e. 'positive' controls. In the first experiment we tested: smouldering H. suaveolens (85.4% repellency); fresh H. suaveolens (73.2%); burning of the bark of D. oliveri (74.7%); and smoke of the leaves of Eucalyptus (72.2%). In the second experiment we tested: smouldering H. suaveolens (83.6% repellency); fresh H. suaveolens (66.5%); burning of the bark of D. oliveri (77.9%); smoke of the leaves of A. indica (76.0%); smoke of the infructescence of E. guineensis (69.0%); fresh O. canum (63.6%); and fresh S. occidentalis; (29.4%). All the products tested, except S. occidentalis were significantly more effective than the negative control.

Paulsen SM. Use of herbal products and dietary supplements by oncology patients--informed decisions? Highlights Oncol Pract 1998;15(4):94-9, 103-6.
IPA COPYRIGHT: ASHP An overview of various herbal products and dietary supplements used in cancer prevention and treatment is presented, including prasterone (dehydroepiandrosterone), green teas, adaptogens such as Echinacea and cat's claw (Uncaria species), bovine cartilage, Larrea tridentata (chaparral), linseed oil (flaxseed oil), Viscum album (mistletoe), pau d'arco (a tea derived from the bark of trees of the Tecoma genus), and shark cartilage as well information on clinical studies and toxicity of these products.

Pepping J. Kava: Piper methysticum. Am J Health Syst Pharm 1999 May 15;56:957-58, 960.
IPA COPYRIGHT: ASHP A brief overview of the pharmacology, pharmacokinetics, dosage, adverse effects, drug interactions, contraindications, and results of clinical studies of kava, an herb used for its anxiolytic and sedative properties, is presented. Kava is derived from the pulverized roots and rhizomes of several subspecies of a pepper plant Piper methysticum.

Pepping J. St. John's Wort: Hypericum perforatum. Am J Health Syst Pharm 1999 Feb 15;56:329-30.
IPA COPYRIGHT: ASHP A brief overview of the pharmacology, dosage, adverse effects, drug interactions, contraindications, and results of clinical studies of Hypericum perforatum (St. John's Wort), an herb used to treat depression, anxiety, and sleep disorders, is presented.

Phillipson D. Pharmacognostical peregrinations. Pharm J 1997 Feb 1;258:176-7.
IPA COPYRIGHT: ASHP An account of one London University pharmacognosy professor's experiences with pharmacists in Australia and Malaysia, where he visited in the autumn of 1996, is presented with a focus on their interest in herbal medicine.

Pittenger J. Herbal treatments find their way into mainstream America. Wis Med J 1997;96(3):30-1.

Posner H. Alternative medicine--the case of herbal remedies [letter]. N Engl J Med 1999;340(7):565; Discussion 566.

Prince CE. Goldenrod (Solidago gigantea, Solidago virgaurea). Nebr Mortar Pestle 1997 Sep;60:8-9.
IPA COPYRIGHT: ASHP The anti-inflammatory properties, toxicity, and results of animal studies of Solidago gigantea and Solidago virgaurea (goldenrod) are discussed.

Qin GW, Xu RS. Recent advances on bioactive natural products from Chinese medicinal plants. Med Res Rev 1998;18(6):375-82.
China has accumulated a rich body of empirical knowledge of the use of medicinal plants for the treatment of various diseases throughout its long history. Chemical studies on Chinese medicinal plants provide a valuable material base for the discovery and development of new drugs of natural origin. In this article recent chemical work on various Chinese medicinal plants is reviewed, including Mussaenda pubescens (Rubiaceae), Isatis indigotica (Cruciferae), Euphorbia fischeriana, and E. ebracteolata (Euphorbiaceae), and Stemona species (Stemonaceae). The structural diversity of the medicinal chemical constituents of the above plants is discussed.

Raja D, Blanche C, Valles Xirau J. Contribution to the knowledge of the pharmaceutical ethnobotany of La Segarra region (Catalonia, Iberian Peninsula). J Ethnopharmacol 1997;57(3):149-60.
An ethnobotanical survey was carried out in the region known as La Segarra, situated at the north east of the Iberian Peninsula, in the inner plains of Catalonia, with an area of 720 km2 and a population of 17000. Working with 29 people, data on uses of 142 species belonging to 54 botanical families were obtained and presented, of which 13 uses corresponding to nine plant species were previously unreported.

Rogers MV, Cheek B. Echinacea (purple coneflower). Carol J Pharm 1997 Jan-Feb;77:16.
IPA COPYRIGHT: ASHP The pharmacology, dosage forms, dosage, and toxicity of Echinacea (purple coneflower) for immunostimulation are discussed.

Rogers PL, Shin HS, Wang B. Biotransformation for L-ephedrine production. Adv Biochem Eng Biotechnol 1997;56:33-59.
L-ephedrine is widely used in pharmaceutical preparations as a decongestant and anti-asthmatic compound. One of the key intermediates in its production is L-phenylacetylcarbinol (L-PAC) which can be obtained either from plants (Ephedra sp.), chemical synthesis involving resolution of a racemic mixture, or by biotransformation of benzaldehyde using various yeasts. In the present review, recent significant improvements in the microbial biotransformation are assessed for both fed-batch and continuous processes using free and immobilised yeasts. From previous fed-batch culture data, maximal levels of L-PAC of 10-12 gl-1 were reported with yields of 55-60% theoretical based on benzaldehyde. However, recently concentrations of more than 22 gl-1 have been obtained using a wild-type strain of Candida utilis. This has been achieved through optimal control of yeast metabolism (via microprocessor control of the respiratory quotient, RQ) in order to enhance substrate pyruvate production and induce pyruvate decarboxylase (PDC) activity. Processes involving purified PDC have also been evaluated and it has been demonstrated that L-PAC levels up to 28 gl-1 can be obtained with yields of 90-95% theoretical based on the benzaldehyde added. In the review the advantages and disadvantages of the various strategies for the microbial and enzymatic production of L-PAC are compared. In view of the increasing interest in microbial biotransformations, L-PAC production provides an interesting example of enhancement through on-line control of a process involving both toxic substrate (benzaldehyde) and end-product (L-PAC, benzyl alcohol) inhibition.

Romano I, Tsourounis C. Saw palmetto (Serenoa repens) for the treatment of benign prostatic hyperplasia. Calif J Health Syst Pharm 1998 May-Jun;10:16-7, 33.
IPA COPYRIGHT: ASHP An overview of the pharmacology, pharmacokinetics, clinical studies, and adverse effects of Serenoa repens (Saw palmetto) for the treatment of benign prostatic hyperplasia is presented.

Saller R, Reichling J, Kristof O. [Phytotherapy--treatment without side effects?]. Dtsch Med Wochenschr 1998;123(3):58-62. (Ger)

Schneck C. St. John's wort and hypomania [letter]. J Clin Psychiatry 1998;59(12):689.

Seifert P. Herbal extracts in cosmetics--opportunities and limitations.Seifen Oele Fette Wachse 1997 Jan;123:28, 30-1.
IPA COPYRIGHT: ASHP Various limitations associated with the opportunities for the fashionable use of herbal extracts in cosmetics are briefly discussed, including differences in the criteria for herbal extracts used in cosmetic and medicinal applications, the criteria for natural cosmetics, utility of the drug extract ratio as a measure of the quality or activity of plant extracts, and standardization of plant extracts.

Shaw D. Risks or remedies? Safety aspects of herbal remedies in the UK. J R Soc Med 1998;91(6):294-6.

Shaw D, Leon C, Murray V, Volans G. Patients' use of complementary medicine [letter]. Lancet 1998;352(9125):408.

Shepard GH Jr. Psychoactive plants and ethnopsychiatric medicines of the Matsigenka. J Psychoactive Drugs 1998;30(4):321-32.
For the Matsigenka of the Peruvian Amazon, health and well-being in daily life depend upon harmonious relationships within the social group and with the spirit world. Psychoactive plants play a crucial role in curing disrupted social relationships while giving humans access to the otherwise remote, parallel world of spirits. Different species and cultivars of psychoactive plants, as well as varying admixtures and doses, are used to obtain different intensities and qualities of psychoactive experience, depending upon the individual's goals. Strongly psychoactive plants are used by shamans to travel to the realm of spirits. A number of mild to strongly psychoactive plants are used by male hunters to purify their souls and improve their aim. Mildly psychoactive plants are used to improve women's concentration for spinning and weaving cotton, to control negative emotions such as grief and anger, to manipulate the content of dreams, and to pacify sick or frightened children. A majority of such remedies come from the botanical families of Rubiaceae, Solanaceae and Cyperaceae, known sources of psychoactive compounds. Interdisciplinary research into the culture, botany and pharmacology of psychoactive plants in indigenous medical systems contributes to a better understanding of the role of psychological states in human health and well-being.

Shinchi K, Ishii H, Imanishi K, Kono S. Relationship of cigarette smoking, alcohol use, and dietary habits with Helicobacter pylori infection in Japanese men. Scand J Gastroenterol 1997;32(7):651-5.
BIOSIS COPYRIGHT: BIOL ABS. Background: Little is known of factors determining infection with Helicobacter pylori. Methods: In a cross-sectional study of 566 men aged 50-55 years, who received a preretirement health examination at the Self Defense Forces Fukuoka Hospital between January 1993 and December 1994, we examined the association of smoking, alcohol use, and dietary habits with H. pylori infection. Results: The overall seropositivity as determined with IgG antibody was 79.3% (449 of 566). The rank was inversely associated with the infection (trend, P = 0.048). Neither smoking nor alcohol drinking was related to the infection. The prevalence adjusted for rank tended to be lower in men consuming raw vegetables (trend, P = 0.12) daily than those with less consumption. Unexpectedly, the consumption of tofu (soybean curd) was significantly, negatively related to the infection (trend, P = 0.013). The seropositivity was unrelated to the consumption of pickled vegetables, soy paste soup, green tea, or garlic. Conclusion: The findings suggest that fresh vegetables may be protective against H. pylori infection. The study does not support either an increased risk of the infection associated with salty foods or a protective effect of green tea or garlic.

Square D. Sage advice from my garden. CMAJ 1998;159(12):1495-7.

Stueland DT, Ault BJ, Gunderson PD. Change in cholinesterase levels and self-reported symptoms over two years. J Agromed 1997; 4(1/2):151-6.
The application and reliability of self reported symptoms and serum cholinesterase (ACH) levels as measures of effects of farm chemical exposures over time were analyzed. Twenty two ginseng producers in central Wisconsin participated in 2 years of on site testing. Each year they reported on farming practices and health seeking behavior and completed a 20 item questionnaire related to possible farm chemical exposure symptoms. Plasma and red cell ACH were also measured. No seizure symptoms were reported. The mean age of participants was 41.5 years. Thirteen of the participants were men and 21 were owner operators. The mean initial plasma ACH levels changed from 16.15 units/milliliter (U/ml) in 1994 to 16.25U/ml in 1995. Red blood cell ACH levels were 37.95U/ml in 1994 and 42.32U/ml in 1995 at the start of the season. In 1994 the follow up study showed an increase to 39.55U/ml, but a decrease in 1995 to 38.80U/ml. Changes in symptoms from 1994 to 1995 correlated with the change in initial plasma ACH levels over the same year. Each year the participants experienced a drop in ACH activity. Self reported symptoms remained highly correlated and showed, overall, only minor changes, suggesting that symptoms and ACH testing may be reliable for on site field testing.

Sukumaran M, Chung H, Gollapudi DP. Cultural factors in the treatment of a catatonic Chinese patient [letter]. Gen Hosp Psychiatry 1997;19(5):378-80.

Tello CG, Ford P, Iacopino AM. In vitro evaluation of complex carbohydrate denture adhesive formulations. Quintessence Int 1998;29(9):585-93.
OBJECTIVE: Acemannan, a complex mannose carbohydrate derived from the aloe vera plant, has an inherent stickiness/viscosity. Prototype Acemannan denture adhesive formulations were evaluated for pH changes, cytotoxicity to human gingival fibroblasts and adhesive strength in both dry and wet conditions. METHOD AND MATERIALS: The denture adhesive formulations consisted of five combinations of Acemannan with varying concentrations of preservatives and two other formulations without preservatives. The pH of each formulation was measured over 24 hours. Assessment of cytotoxicity was accomplished using the in vitro, tetrazolium-based colorimetric assay on cultures of human gingival fibroblasts after exposure to the adhesive formulations for up to 24 hours. The adhesive strength was evaluated with a universal testing machine under initial dry conditions and after immersion in a constant-temperature water bath for up to 20 minutes. RESULTS: Formulations 1 and 2 achieved and maintained pH values above 6.0 (the critical pH for hydroxyapatite dissolution) approximately 6 hours into the study. None of the prototypes demonstrated an initial pH above the critical pH. Formulations 1, 2, 3, and 5 exhibited significant cytotoxicity to human gingival fibroblasts over 24 hours. Formulations 4, 20:1, and 150:1 demonstrated minimal cytotoxicity. Formulation 1 exhibited the poorest adhesive strength, while the most viscous formulation (prototype 150:1) was by far the best performer. Generally, adhesive bond strengths for all prototypes were quite high and relatively stable over time in a wet environment. CONCLUSION: To achieve the ideal adhesive in terms of strength, pH, and cytotoxicity, Acemannan formulation 150:1 should be adjusted to contain the preservative concentration of formulation 4 and have an initial pH value of 6.0 or higher.

Thompson CA. As patients embrace herbal remedies, dearth of scientific evidence frustrates clinicians. Am J Health Syst Pharm 1997 Dec 1;54:2656, 2658, 2664.
IPA COPYRIGHT: ASHP Sources of information regarding the efficacy and side effects of herbal remedies for physicians and pharmacists are described, clinical studies evaluating the efficacy of some herbal products are summarized, and differences between formulations of herbal products that may affect the efficacy of the product are discussed.

Thompson CA. USP moves forward in providing information on botanical products [news]. Am J Health Syst Pharm 1998;55(6):527, 530.

Thornton Z. Health care the herbal way. East Pharm 1997 Aug;40:71-2.
IPA COPYRIGHT: ASHP A brief overview of the therapeutic use of herbal medicines is presented, and adverse reactions, self-medication, and the quality control of herbal products are considered.

Turow V. Herbal therapy for children [letter]. Pediatrics 1998;102(6):1492-3.

Van Rensen I, Blume H, Ihrig M, Morck H, Dingermann T, Veit M. [Evaluation of phytopharmaceuticals in pharmacy practice]. Pharm Ztg 1998 Feb 19;143:11-8, 21. (Ger)
IPA COPYRIGHT: ASHP An overview of phytopharmaceuticals, including nomination and standardization of pharmaceutical quality, efficacy, clinical research, therapy study types and designs, safety critiques, terms of registration, and advertisements, is presented; it was noted that patients need the expertise of the counseling pharmacist in regard to herbal medication.

Vann A. The herbal medicine boom: understanding what patients are taking [see comments]. Cleve Clin J Med 1998;65(3):129-34.

Varga CA, Veale DJ. Isihlambezo: utilization patterns and potential health effects of pregnancy-related traditional herbal medicine. Soc Sci Med 1997;44(7):911-24.
Isihlambezo is a herbal decoction used by many Zulu women in South Africa as a preventative health tonic during pregnancy. Though the practice is cited by ethnographers and medical practitioners, few studies have focused on specific elements of isihlambezo use and preparation. Moreover, though some evidence exists suggesting negative effects of its ingestion, the maternal-fetal health impact and toxicity of isihlambezo have not been adequately studied. We examined two aspects of this traditional antenatal health practice: (1) the potential impact of urbanization and access to Western clinic-based care on popularity and utilization patterns of isihlambezo, and (2) the potential maternal-fetal health effects of its use. Interviews were conducted among rural and urban women in clinic and non-clinic settings regarding socio-behavioral aspects of isihlambezo use. The pharmacology of certain plant ingredients of isihlambezo was investigated through laboratory assays, literature review, and interviews with traditional healers. There were significant differences by area of interview in nearly all aspects of isihlambezo use examined. Though isihlambezo was most popular among urbanites and clinic non-attenders, it was considered an important antenatal health care alternative by the majority of women surveyed. Mixing traditional and clinic-based antenatal care was also strongly advocated. Pharmacological analysis suggested the possibility of both therapeutic and harmful consequences of isihlambezo. It was suggested that the following factors might contribute the popularity of isihlambezo among urban women: high cost and inferior quality of clinic care, use of isihlambezo as a means of adapting to urbanization-related stress, and socio-cultural transition.

Vazquez FM, Suarez MA, Perez A. Medicinal plants used in the Barros Area, Badajoz Province, Spain. J Ethnopharmacol 1997;55(2):81-5.
A study of the wild and cultivated medicinal plants used in the Barros Area (southern Spain) is reported, 48 plants distributed among 20 different families are used in the treatment of various human diseases. The use of Bellis annua L. Centaurea ornata Wild., Leuzea conifera (L.) DC., Pulicaria paludosa Link and Asparagus aphyllus L. is reported.

Williamson JS, Wyandt CM. Herbal therapies: facts and the fiction. Drug Top 1997 Aug 4;141:78-87.
IPA COPYRIGHT: ASHP An overview of herbal therapies is presented, including the history of disease treatment with herbal remedies, counseling patients about the appropriate use of herbal products, and the risks and benefits of common herbal remedies such as Medicago sativa (alfalfa), Aloe vera (aloe vera), Arnica montana (arnica), Vaccinium myrtillus (bilberry), Uncaria tomentosa (cat's claw), Angelica sinensis (dong quai), Echinacea purpurea (echinacea), Ephedra sinica (ephedra), Chrysanthemum parthenium (feverfew), Allium sativum (garlic), Ginkgo biloba (ginko biloba), Panax ginseng (ginseng), hypericum perforatum (St. John's wort), and Serenoa repens (saw palmetto). A table of the purported properties and uses of 153 herbs is provided. This article qualifies for 2 hours U.S. CE credit by the ACPE.

Williamson JS, Wyandt CM. Herbal update. Drug Top 1998 Jun 1;142:66-75.
IPA COPYRIGHT: ASHP The rational use and contraindications of herbal therapy, patient information, drug interactions, and the legal status of herbal preparations are presented including popular American and European herbs such as Aloe vera, Arnica montana, Vaccinium myrtillus (bilberry), Uncaria tomentosa (cat's claw), Angelica sinensis (Dong quai), Echinacea purpurea, evening primrose oil, Tanacetum parthenium (feverfew), Allium sativum, Zingiber officinale (ginger), Ginkgo biloba, Panax ginseng, Crataegus species (hawthorn), Aesculus hippocastanum, Piper methysticum (kava-kava), Silybum marianum, Hypericum perforatum (St. John's wort), Serenoa species (Saw palmetto), and Valeriana officinalis (Valerian). This article qualifies for 2 hours U.S. CE credit by the ACPE.

Williamson JS, Wyandt CM. What the pharmacist should know about food and drug interactions. Hosp Pharm Rep 1998 Apr;12:43-52.
IPA COPYRIGHT: ASHP An overview of the effects of food, tobacco, ethyl alcohol, and herbal products on drug action is presented, including a discussion of the mechanisms of drug-food interactions, counseling patients about when it is appropriate to take a drug with food and when it is contraindicated, counseling patients about the effects of alcohol and tobacco use on drug action, and potentially significant food-drug interactions involving nutritional agents, hormonal agents, respiratory agents, diuretics/cardiovascular agents, anti-infective agents, GI agents, CNS agents, antineoplastic agents, immunosuppressive agents, and dietary supplements. This article qualifies for 2 hours U.S. CE credit by the ACPE.

Winkelaar PG. Medicolegal file. Tacit approval of alternative therapy. Can Fam Physician 1999;45:905.

Winston D, Dattner AM. The American system of medicine. Clin Dermatol 1999;17(1):53-6.

Wong HC. Is feverfew a pharmacologic agent? [letter]. CMAJ 1999;160(1):21-2.

Wright R, Vanvuren B. Ginkgo biloba. Nebr Mortar Pestle 1997 Jun;60:10-1.
IPA COPYRIGHT: ASHP An overview of Ginkgo biloba, from a tree native to China and an herbal remedy used for 5000 yr, is presented, including its mechanism of action, therapeutic use in conditions associated with decreased peripheral and cerebral vascularity such as cerebral ischemia, its pharmacodynamics, dosage, adverse effects, and potential drug interactions. It is noted that in Germany and France, Ginkgo biloba is among the most commonly prescribed drugs, while in the United States it is available as an OTC natural product.

Wynn RL, Meiller TF. A brief survey of herbal medicines and other remedies. Gen Dent 1997;45(2):112-5.

Xue T, Zhang L. Avenues of discovery in bioprospecting [letter; comment]. Nature 1998;393(6686):617.

Zhang YY, Don HY, Guo YZ, Ageta H, Harigaya Y, Onda M, Hashimoto K, Ikeya Y, Okada M, Maruno M. Comparative study of Scutellaria planipes and Scutellaria baicalensis. Biomed Chromatogr 1998;12(1):31-3.
Scutellaria planipes, a species of Scutellaria, was explored by comparing to Scutellaria baicalensis, a pharmacopoeia species. Four principle flavonoids in both the plant roots were analyzed by using a reversed-phase chromatographic system with a chemically bonded ODS silica gel column and phosphate buffer:methanol (68:32 and 1:1) as mobile phase. Their contents were similar in both plant roots. Antiallergic and antibacterial activities in vitro and acute toxicity were compared. The results provided valuable data for S. planipes as a potential medicinal resource.

Zink T, Chaffin J. Herbal 'health' products: what family physicians need to know [see comments]. Am Fam Physician 1998;58(5):1133-40.
Patients who self-medicate with herbs for preventive and therapeutic purposes may assume that these products are safe because they are "natural," but some products cause adverse effects or have the potential to interact with prescription medications. The United States lacks a regulatory system for herbal products. Although only limited research on herbs has been published, St John's wort shows promise as a treatment for depression. Ginkgo biloba extract is possibly effective for cerebrovascular insufficiency and dementia. Feverfew is used extensively in Canada for migraine prophylaxis but needs more rigorous study. Ephedrine has been regulated by many states because its misuse has been associated with several deaths. Echinacea is being tried as an agent for immune stimulation, and garlic is under study for cholesterol-lowering properties, but both require more study. Physicians should educate themselves and their patients about the efficacy and adverse interactions of herbal agents and the limitations of our present knowledge of them.

. Phytotherapy: how to minimize risks. Presc Intl 1997;6(27):25-6.
IPA COPYRIGHT: ASHP Various ways to minimize risks associated with herbal remedy therapies are described, including an overview of adverse effects associated with various herbal remedies, the need for health professionals to be aware of unreliable labels on plant based products as well as contamination potential, and the levels of regulatory control that exist on herbal remedies in France.

. Pulmonary embolism with a plant based product. Presc Intl 1997;6(31):144.
IPA COPYRIGHT: ASHP The removal of a plant based formulation from the market in France following its implication in a case of deep vein thrombosis and pulmonary embolism in an infant, and the importance of removing herbal products with no guarantees of efficacy and safety from pharmacy shelves are briefly discussed.

Abdel-Hafez AA, Meselhy MR, Nakamura N, Hattori M, Watanabe H, Murakami Y, El-Gendy MA, Mahfouz NM, Mohamed TA. Effects of paeoniflorin derivatives on scopolamine-induced amnesia using a passive avoidance task in mice; structure-activity relationship. Biol Pharm Bull 1998;21(11):1174-9.
Paeoniflorin (1) and its derivatives having in common a cage-like pinane skeleton with hemiketal-acetal system, were evaluated for their effects on memory impairment induced by scopolamine in mice using a step-down type passive avoidance task. In the test session, 1 and its derivatives were intraperitoneally (i.p.) administered at doses of 0.002, 0.01, 0.02 and 0.2 mmol/kg, and 30 min later (15 min before the experiment), scopolamine (1 mg/kg, i.p.) was given. These compounds showed dose-dependent attenuation in a dose range of 0.002-0.02 mmol/kg and also enhancement of scopolamine-induced decrease in step-down latency. The effects of these compounds, except that of 2',3',4',5'-O-tetraacetyl-3-O-methylpaeoniflorin (8), followed a bell-shaped dose response profile. 8-Debenzoyl-6-deglucosyl-3-O-methylpaeoniflorin (6) showed no significant increase in the step-down latency at all tested doses. Maximum step-down latency was obtained by 3-O-methylpaeoniflorin (3) and 2',3,3',4',5'-penta-O-methylpaeoniflorin (7) (the minimal effective dose was 0.002 mmol/kg). Relative to 3, debenzoylation, as in 8-debenzoyl-3-O-methylpaeoniflorin (4), slightly increased the latency, while deglucosylation, as in 6-deglucosyl-3-O-methylpaeoniflorin (5), significantly reduced the prolongation of latency. Removal of both glucose and benzoyl moieties resulted in the loss of activity as seen in 6. These results revealed that, in addition to the cage-like pinane skeleton, the benzoyl and the glucosyl moieties are important structural elements of the paeoniflorin skeleton as its effects on scopolamine-induced amnesia.

Al-Fakhri SA. Herbal medicine: possible cause of aspiration pneumonia: case report. Saudi Pharm J 1998;6(1):88-91.
IPA COPYRIGHT: ASHP The case report of a 3-wk-old girl who developed aspiration pneumonia possibly due to aspiration of an herbal medicine in powder form consisting of Commiphora molmol (myrrh), Ferula foetida L. (apiacea), Astragalus sarcocolla, and Saccharum officinarum Linne. is presented. The child was successfully treated with nebulized albuterol (salbutamol) and budesonide and oral prednisolone.

Al-Suwaidan SN, Gad El Rab MO, Al-Fakhiry S, Al Hoqail IA, Al-Maziad A, Sherif AB. Allergic contact dermatitis from myrrh, a topical herbal medicine used to promote healing. Contact Dermatitis 1998;39(3):137.

Aldana L, Gonzalez De Mejia E, Craigmill A, Tsutsumi V, Armendariz-Borunda J, Panduro A, Rincon AR. Cypermethrin increases apo A-1 and apo B mRNA but not hyperlipidemia in rats. Toxicol Lett 1998;95(1):31-9.
The hepatotoxic effect of cypermethrin and the expression of hepatic genes at the mRNA level, as molecular markers of liver damage, were evaluated in rats following exposure to cypermethrin. The expression of hepatic genes was compared with conventional liver functional tests, and correlations were made by studying the liver at the ultrastructural level. Cypermethrin treated rats presented a significant decrease, of 79% and 22%, on the expression of albumin and apo E genes at 5 days, respectively. The levels of apo A-1 and apo B mRNA were increased up to four- and fivefold, respectively. This increase did not correlate with the serum values of HDL and VLDL lipoprotein particles. Intracytoplasmic lipid droplets were observed after the first 2 days following cypermethrin administration, suggesting that apo A-1 and B mRNA were translated but not secreted. There were significant correlations between the low values of the albumin gene expression, the decrease in the HDL concentrations, and the ultrastructural alterations, respectively. These alterations were mainly a large amount and increased size of mitochondria in the animals exposed to cypermethrin. It is concluded that under the experimental conditions used, cypermethrin may alter the metabolism of lipids and proteins in rat liver.

Alexander RG, Wilson DA, Davidson AG. Medicines Control Agency investigation of the microbial quality of herbal products. Pharm J 1997 Aug 16;259:259-61.
IPA COPYRIGHT: ASHP To assess the microbiological quality of licensed herbal products by determining the nature and quantity of microorganisms present, 425 herbal products were examined by pharmacopeial and validated inhouse methods; total aerobic bacterial counts and total fungal counts were measured. Most licensed herbal products were found to comply with European Pharmacopeial limits. However, some solid oral dosage forms were found to contain undesirable organisms. It was suggested that additional quantitative tests for specific microorganisms in future editions of the European Pharmacopeia may be justified.

Alpertunga B, Omurtag GZ, Ozmentese N. Investigation about the genotoxic activities of some herbal teas used as folk medicine. Acta Pharm Turc 1997;39(3):105-10.

Ameri A. The effects of Aconitum alkaloids on the central nervous system. Prog Neurobiol 1998;56(2):211-35.
Preparations of Aconitum roots are employed in Chinese and Japanese medicine for analgesic, antirheumatic and neurological indications. The recent surge in use of phytomedicine derived from traditional Chinese medicine as well as increasing concerns about possible toxic effects of these compounds have inspired a great deal of research into the mechanisms by which certain Aconitum alkaloids may act on the central nervous system. The pharmacological effects of preparations of Aconitum roots are attributed to several diterpenoid alkaloids. The main alkaloid of these plants is aconitine, a highly toxic diterpenoid alkaloid which is known to suppress the inactivation of voltage-dependent Na+ channels by binding to neurotoxin binding site 2 of the alpha-subunit of the channel protein. In this article the pharmacology of several structurally related Aconitum alkaloids is highlighted and their therapeutic vs toxic potential is discussed. Neurochemical and neurophysiological studies will be reviewed with emphasis on the effects of the alkaloids in regions of the brain that have been implicated in pain transmission and generation of epileptic activity. Considering the chemical structure of the Aconitum alkaloids as well as their mechanism of action, a subdivision in three groups becomes obvious: the first group comprises such alkaloids which possess high toxicity due to two ester boundings at the diterpene skeleton. The members of this group activate voltage-dependent sodium channels already at resting potential and inhibit noradrenaline reuptake. Activation of sodium channels and in consequence excessive depolarization with final inexcitability and suppression of pain transmission account for their antinociceptive properties. The second group comprises less toxic monoesters which have been shown to possess strong antinociceptive, antiarrhythmic and antiepileptiform properties due to a blockade of the voltage-dependent sodium channel. Electrophysiological studies have revealed a use-dependent inhibition of neuronal activity by these alkaloids. They seem to be competitive antagonists of the group I-alkaloids. The third group of Aconitum alkaloids are lacking an ester side chain in the molecule. Toxicity is markedly reduced when compared with the two other groups. They fail to affect neuronal activity, but are reported to have antiarrhythmic actions suggesting that they may have different affinities to various subtypes of the alpha-subunit of the Na+ channel in brain and heart.

Angell M, Kassirer JP. Alternative medicine--risks of untested and unregulated remedies. N Engl J Med 1998 Sep 17;339:839-41.
IPA COPYRIGHT: ASHP The risks of untested and unregulated herbal medicine, the most common of all forms of alternative medicine, are discussed.

Anibarro B, Fontela JL, De La Hoz F. Occupational asthma induced by garlic dust. J Allergy Clin Immunol 1997;100(6 Pt 1):734-8.
BACKGROUND: Garlic dust has not been a frequently encountered cause of IgE-mediated disease. OBJECTIVE: We report on 12 patients (all of them garlic workers) with the clinical criteria for occupational asthma. METHODS: Skin prick tests and serum-specific IgE determinations were performed with common inhalants, garlic, and other members of the Liliaceae family (onion, leek, and asparagus). Bronchial challenge test with garlic powder was performed in all patients. Garlic and onion extract proteins were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Immunoblot and IgE immunoblot inhibition analyses were performed with patients' sera on extracts of garlic, onion, and pollens of Phleum pratense and Chenopodium album. RESULTS: Garlic sensitization was demonstrated by bronchial challenge test in seven patients (group 1) and ruled out in the remaining five (group 2). Clinical data were similar in both groups. The patients with garlic allergy had a mean age of 27 years, and all of them had pollen allergy; sensitization to other members of the Liliaceae family was also common. Electrophoresis of garlic extract revealed two major protein bands at approximately 12 and 54 kd. During IgE immunoblotting, the pool of sera reacted with garlic proteins mainly at 54 kd. Preincubation with onion, Phleum, and Chenopodium partially abolished the IgE binding to several allergens of garlic. CONCLUSION: We report on seven patients in whom an occupational garlic allergy was demonstrated. Garlic allergy is relatively rare but seems to affect young subjects with pollen allergy, and sensitization to other members of the Liliaceae family is common. The results of this study confirm the presence of some structurally similar allergens in garlic, onion, and certain pollens.

Aphale AA, Chhibba AD, Kumbhakarna NR, Mateenuddin M, Dahat SH. Subacute toxicity study of the combination of ginseng (Panax ginseng) and ashwagandha (Withania somnifera) in rats: a safety assessment. Indian J Physiol Pharmacol 1998;42(2):299-302.
Ginseng (Panax ginseng) and Ashwagandha (Withania somnifera) are widely used as geriatric tonics. Both individually have not shown any toxicity on long term administration. Study was planned to assess the safety of the combination by doing subacute toxicity study in rats with 90 days oral administration using three doses. Food consumption, body weight, haematological, biochemical and histopathological parameters were studied. There was significant increase in body weight, food consumption and liver weight, and improved hematopoiesis was observed. Brain, heart, lung, liver, spleen, kidneys, stomach, testis and ovaries were normal on gross examination and histopathologically. Subacute toxicity studies in rats did not reveal any toxicity.

Apted J. Primin sensitivity in a patient sensitive to Streptocarpus [letter]. Australas J Dermatol 1998;39(3):199-200.

Asero R. Relevance of pollen-specific IgE levels to the development of Apiaceae hypersensitivity in patients with birch pollen allergy. Allergy 1997;52(5):560-4.
A large clinical/serologic study was carried out to determine the prevalence of Apiaceae (carrot, celery, and fennel) hypersensitivity in patients with birch pollen allergy, and to investigate its relationship with apple and hazelnut allergy and with birch pollen-specific IgE levels. A total of 196 birch pollen-hypersensitive patients with oral allergy syndrome (OAS) caused by different vegetable foods were examined in the cross-sectional part of the study. Of this total, 195 patients had apple and/or hazelnut allergy, and 103 had Apiaceae sensitivity; only one patient had Apiaceae allergy alone. Apiaceae-positive patients showed significantly higher birch pollen-specific IgE levels than negative ones (median 13 vs 7 AU/ml; P < 0.0001). The prospective part of the study was performed on 103 birch pollen-hypersensitive patients who were OAS-free at the time of the first visit and were periodically followed-up for OAS. Patients who developed Apiaceae sensitivity showed much higher birch-specific IgE levels than patients who developed apple/hazelnut allergy only (median 15.5 vs 8.5 AU/ml; P < 0.05), whereas those who remained OAS-free showed the lowest specific IgE levels (median 5 AU/ml). This study suggests that most Apiaceae determinants cross-react with apple or hazelnut determinants, whereas only some apple or hazelnut determinants cross-react with Apiaceae-allergenic determinants; moreover, it shows that birch-specific IgE levels heavily influence the onset of OAS as a whole, and probably play a critical role in the development of allergies to distinct vegetable foods as well.

Asero R, Mistrello G, Roncarolo D, Antoniotti PL, Falagiani P. A case of garlic allergy. J Allergol Clin Immunol 1998;101(3):427-28.
BIOSIS COPYRIGHT: BIOL ABS. RRM CASE STUDY ALLIUM-SATIVUM HUMAN ADULT FEMALE GARLIC ALLERGY ALLERGY URTICARIA DERMATOLOGY IMMUNE SYSTEM DISEASE INTEGUMENTARY SYSTEM DISEASE.

Avila H, Rivero J, Herrera F, Fraile G. Cytotoxicity of a low molecular weight fraction from Aloe vera (Aloe barbadensis Miller) gel. Toxicon 1997;35(9):1423-30.
The cytotoxicity of a low mol. wt fraction (LMWF) obtained from Aloe vera gel was determined by two different assays. Firstly, exposure of monolayers of chicken fibroblasts to LMWF induced disruption of intercellular junctions and detachment of individual cells from the bottom of the flask, with formation of cell-free gaps in the monolayer. Secondly, LMWF inhibited the production of reactive oxygen species by human polymorphonuclear leukocytes stimulated by zymosan, as followed by luminol-dependent chemiluminescence. The toxic activity of LMWF was compared to that of sodium dodecyl sulfate (a well-known toxic substance), aloe-emodin and aloin (an anthraquinone and its precursor present in Aloe vera cortex) using the chemilumescence assay, and was found to be of similar potency to these toxic substances on a weight-to-weight basis. These results confirm that Aloe vera gel contains toxic low mol. wt compounds, and every effort must be made to limit the amount of these toxins in the commercially prepared Aloe vera gel products.

Bagheri H, Broue P, Lacroix I, Larrey D, Olives JP, Vaysse P, Ghisolfi J, Montastruc JL. Fulminant hepatic failure after herbal medicine ingestion in children [letter]. Therapie 1998;53(1):82-3.

Barnes J, Mills SY, Abbot NC, Willoughby M, Ernst E. Different standards for reporting ADRs to herbal remedies and conventional OTC medicines: face-to-face interviews with 515 users of herbal remedies. Br J Clin Pharmacol 1998;45(5):496-500.
AIMS: To determine whether adverse drug reactions (ADRs) to herbal remedies would be reported differently from similar ADRs to conventional over-the-counter (OTC) medicines by herbal-remedy users. METHODS: Face-to-face interviews (using a structured questionnaire) with 515 users of herbal remedies were conducted in six pharmacy stores and six healthfood stores in the UK. The questionnaire focused on the likely course of action taken by herbal-remedy users after experiencing an ADR associated with a conventional OTC medicine and a herbal remedy. RESULTS: Following a 'serious' suspected ADR, 156 respondents (30.3%) would consult their GP irrespective of whether the ADR was associated with the use of a herbal remedy or a conventional OTC medicine, whereas 221 respondents (42.9%) would not consult their GP for a serious ADR associated with either type of preparation. One hundred and thirty-four respondents (26.0%) would consult their GP for a serious ADR to a conventional OTC medicine, but not for a similar ADR to a herbal remedy, whereas four respondents (0.8%) would consult their GP for a serious ADR to a herbal remedy, but not for a similar ADR to a conventional OTC medicine. Similar differences were found in attitudes towards reporting 'minor' suspected ADRs. CONCLUSIONS: Consumers of herbal remedies would act differently with regard to reporting an ADR (serious or minor) to their GP depending on whether it was associated with a herbal remedy or a conventional OTC medicine. This has implications for herbal pharmacovigilance, particularly given the increasing use of OTC herbal remedies. The finding that a high proportion of respondents would not consult their GP or pharmacist following ADRs to conventional OTC medicines is also of concern.

Bateman J, Chapman RD, Simpson D. Possible toxicity of herbal remedies. Scott Med J 1998;43(1):7-15.
Herbal remedies are rapidly gaining popularity throughout the world as a result of dissatisfaction with conventional medicines. It is a widely held belief that herbal preparations are "natural" and are therefore intrinsically harmless. However, their effects can be very powerful and potentially lethal if used incorrectly and their use as a substitute for conventional medicines may be ineffective. Toxic effects have been attributed to several factors including hepatotoxicity of main constituents, contamination of preparations by heavy metals or microorganisms, and adverse reactions due to age, and genetic and concomitant disease characteristics of the user.

Bernd A, Simon S, Ramirez Bosca A, Kippenberger S, Diaz Alperi J, Miquel J, Villalba Garcia JF, Pamies Mira D, Kaufmann R. Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen. Photochem Photobiol 1999;69(2):218-21.
Extracts of Hypericum perforatum (St. John's wort) are used in the treatment of depression. They contain the plant pigment hypericin and hypericin derivates. These compounds have light-dependent activities. In order to estimate the potential risk of phototoxic skin damage during antidepressive therapy, we investigated the phototoxic activity of hypericin extract using cultures of human keratinocytes and compared it with the effect of the well-known phototoxic agent psoralen. The absorbance spectrum of our Hypericum extract revealed maxima in the whole UV range and in parts of the visible range. We cultivated human keratinocytes in the presence of different Hypericum concentrations and irradiated the cells with 150 mJ/cm2 UVB, 1 J/cm2 UVA or 3 h with a white light of photon flux density 2.6 mumol m-2 s-1. The determination of the bromodeoxyuridine incorporation rate showed a concentration- and light-dependent decrease in DNA synthesis with high hypericin concentrations (> or = 50 micrograms/mL) combined with UVA or visible light radiation. In the case of UVB irradiation a clear phototoxic cell reaction was not detected. We found phototoxic effects even with 10 ng/mL psoralen using UVA with the same study design as in the case of the Hypericum extract. These results confirm the phototoxic activity of Hypericum extract on human keratinocytes. However, the blood levels that are to be expected during antidepressive therapy are presumably too low to induce phototoxic skin reactions.

Betz JM, Andrzejewski D, Troy A, Casey RE, Obermeyer WR, Page SW, Woldemariam TZ. Gas chromatographic determination of toxic quinolizidine alkaloids in blue cohosh Caulophyllum thalictroides (L.) Michx. Phytochemical Analysis 1998;9(5):232-6.
BIOSIS COPYRIGHT: BIOL ABS. Blue cohosh (Caulophyllum thalictroides (L.) Michx., Berberidaceae) is a North American perennial herb which is found as an ingredient in dietary supplement products in the United States. The plant contains the alkaloids N-methylcytisine, baptifoline, anagyrine and magnoflorine. Some of the alkaloids, including the quinolizidine alkaloid anagyrine, are toxic to range animals and have been implicated as teratogens in higher animals. Since the traditional use of the herb involves administration to women of reproductive age to treat menstrual cramps, and to pregnant women la the last 3-4 weeks of pregnancy to ease parturition, therefore the safety of these products to the fetus is of concern. Three of these alkaloids have been determined in authentic blue cohosh and several dietary supplements. Levels found were: 5-850 ppm for N-methylcytisine, 2-390 ppm for anagyrine, and 9-900 ppm for baptifoline. The lower alkaloid concentrations were found in products containing liquid extracts. Alkaloid identities were confirmed by mass spectrometry.

Bieler CA, Stiborova M, Wiessler M, Cosyns JP, Van Ypersele De Strihou C, Schmeiser HH. 32P-post-labelling analysis of DNA adducts formed by aristolochic acid in tissues from patients with Chinese herbs nephropathy. Carcinogenesis 1997;18(5):1063-7.
Recently, we reported that aristolochic acid (AA) a naturally occurring nephrotoxin and carcinogen is implicated in a unique type of renal fibrosis, designated Chinese herbs nephropathy (CHN). Indeed, we identified the principal aristolochic acid-DNA adduct in the kidney of five such patients. We now extend these observations and demonstrate the presence of additional AA-DNA adducts by the 32P-post-labelling method not only in the kidneys, but also in a ureter obtained after renal transplantation. Using the nuclease P1 version of the assay not only the major DNA adduct of aristolochic acid, 7-(deoxyadenosin-N6-yl)-aristolactam I (dA-AAI), but also the minor adducts, 7-(deoxyguanosin-N2-yl)-aristolactam I (dG-AAI) and 7-(deoxyadenosin-N6-yl)-aristolactam II (dA-AAII) were detected, and identified by cochromatographic analyses with TLC and HPLC. Quantitative analyses of six kidneys revealed relative adduct levels from 0.7 to 5.3/10(7) for dA-AAI, from 0.02 to 0.12/10(7) for dG-AAI and 0.06 to 0.24/ 10(7) nucleotides for dA-AAII. The detection of the dA-AAII adduct is consistent with the occurrence of aristolochic acid II (AAII) in the herb powder imported under the name of Stephania tetrandra and confirms that the patients had indeed ingested the natural mixture of AAI and AAII. 32P-post-labelling analyses of further biopsy samples of one patient showed the known adduct pattern of AA exposure not only in the kidney, but also in the ureter, whereas in skin and muscle tissue no adduct spots were detectable. In an attempt to explain the higher level of the dA-AAI adduct compared to the dG-AAI adduct level in renal tissue even 44 months after the end of regimen, the persistence of these two purine adducts was investigated in the kidney of rats given a single oral dose of pure AAI. In contrast to the dG-AAI adduct, the dA-AAI adduct exhibited a lifelong persistence in the kidney of rats. Our data demonstrate that AA forms DNA adducts in human tissue by the same activation mechanism(s) reported from animal studies. Thus, the carcinogenic/mutagenic activity of AA observed in animals could also be responsible for the urothelial cancers observed in two of the CHN patients.

Blanc PD, Kuschner WG, Katz PP, Smith S, Yelin EH. Use of herbal products, coffee or black tea, and over-the-counter medications as self-treatments among adults with asthma. J Allergy Clin Immunol 1997;100(6 Pt 1):789-91.
BACKGROUND: There are few data on the use of alternative therapies in adult asthma and their impact on health outcomes. OBJECTIVE: The objective of this study was to study the prevalence and morbidity of asthma self-treatment with herbs, coffee or black tea, and over-the-counter (OTC) medications containing ephedrine or epinephrine. METHODS: We carried out a cross-sectional analysis of interview data for 601 adults with asthma recruited from a random sample of pulmonary and allergy specialists. We estimated the 12-month prevalence of reported use of herbal products, coffee or black tea, or OTC products to self-treat asthma and their association with emergency department visits and hospitalization. RESULTS: Herbal asthma self-treatment was reported by 46 (8%; 95% confidence interval [CI] 6% to 10%); coffee or black tea self-treatment by 36 (6%; 95% CI 4% to 8%), epinephrine or ephedrine OTC use by 36 (6%; 95% CI 4% to 8%), and any of the three practices by 98 subjects (16%; 95% CI 13% to 19%). Adjusting for demographic and illness covariates, herbal use (odds ratio [OR] 2.5; 95% CI 1.1 to 5.6) and coffee or black tea use (OR 3.1; 95% CI 1.2 to 7.8) were associated with asthma hospitalization; OTC use was not (OR 0.8; 95% CI 0.3 to 2.5). CONCLUSIONS: Even among adults with access to specialty care for asthma, self-treatment with nonprescription products was common and was associated with increased risk of reported hospitalization. This association does not appear to be accounted for by illness severity or other disease covariates. It may reflect delay in utilization of more efficacious treatments.

Borins M. The dangers of using herbs. What your patients need to know. Postgrad Med 1998;104(1):91-5, 99-100.
Herbal remedies are becoming increasingly popular among patients as treatment for such varied medical problems as arthritis, depression, diabetes, menstrual irregularity, and pulmonary conditions. However, there are many negative effects of herbal preparations. Dr Borins discusses the potential side effects of various herbs and the lack of standardization and control that can contribute to contamination and toxicity of herbal products.

Bove GM. Acute neuropathy after exposure to sun in a patient treated with St. John's Wort. Lancet 1998 Oct 3;352:1121-2.
IPA COPYRIGHT: ASHP The case of a 35-yr-old woman who took 500 mg of Hypericum perforatum as a ground preparation daily for mild depression, based on information in a magazine article, and developed subacute polyneuropathy after exposure to the sun is presented. After 4 wk of taking H. perforatum, the patient developed stinging pain on her face and the dorsum of each hand, which were areas that had received sun exposure. She sought help when the same symptoms developed on the exposed areas of her arms and legs a few h after sunbathing. The patient was diagnosed with subacute toxic neuropathy. H. perforatum was stopped. The symptoms began to improve after 3 wk and disappeared gradually over the next 2 months.

Boyle FM. Adverse interaction of herbal medicine with breast cancer treatment [letter; comment]. Med J Aust 1997;167(5):286.

Brockmoller J, Reum T, Bauer S, Kerb R, Hubner WD, Roots I. Hypericin and pseudohypericin: pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 1997;30(Suppl 2):94-101.
Extracts of St. John's wort (Hypericum perforatum) are used in treatment of depression. They contain various substances with the naphthodianthrones hypericin and pseudohypericin as characteristic ingredients. These compounds were shown to cause phototoxicity in cell culture and in animals. A placebo-controlled randomized clinical trial with monitoring of hypericin and pseudohypericin plasma concentration was performed to evaluate the increase in dermal photosensitivity in humans after application of high dose hypericum extracts. The study was divided into a single dose and a multiple dose part. In the single dose period, each of 13 volunteers received in a double blind fourfold complete crossover design, either placebo, or 900, 1800 or 3600 mg of a standardized hypericum extract (LI 160) containing zero, 2.81, 5.62 and 11.25 mg of total hypericin (total hypericin is the sum of hypericin and pseudohypericin). Maximum total hypericin plasma concentrations were observed about 4 h after dosage and were 0, 0.028, 0.061 and 0.159 mg/L, respectively. Before and 4 h after drug intake, the subjects were exposed at small areas of their back to increasing doses of solar simulated irradiation (SSI, with combined ultraviolet A, UV-A, and UV-B light) and another part was exposed to selective UV-A light irradiation. Minimal erythema dose was determined 5, 20 and 68 h after irradiation. Comparison of SSI sensitivity without and with hypericum extract did not show and difference and there was no dose-related trend in light sensitivity. Sensitivity to selective UV-A light was increased only after the highest dose from a minimal tanning dose of 10.8 J/ cm2 (mean) after placebo to 8.7 J/cm2 after 3600 mg extract with marginal statistical significance (p = 0.03 by one sided paired t-test). There was no correlation between total hypericin plasma concentrations and photosensitivity. In the multiple dose part, 50 volunteers received 600 mg hypericum extract t.i.d. with a daily dose of 5.6 mg of total hypericin. Comparison of UV light sensitivity before dosing with day 15 of treatment showed a slightly increased SSI sensitivity expressed by decrease of the MED from 0.17 to 0.16 J/cm2 (p = 0.005 by Wilcoxon test), and similarly, sensitivity to UV-A light increased (the mean tanning dose decreased from 9.9 to 7.8 J/cm2, p < 0.0001). This increase in cutaneous light sensitivity could be compensated by reducing irradiation time by 21%. Doses used in this study were higher than typical doses in current commercial preparations. In spite of these high doses in the double blind single dose part, frequency of side effects was equal to placebo medication and UV light sensitivity was not or only marginally increased. The study does not, however, exclude phototoxic reactions with doses above 11.25 mg of total hypericin and plasma levels above 100 micrograms/L. Furthermore, phototoxicity may be different after application of pure hypericin, since some constituents in the plant extract may exhibit protective effects.

Brusick D, Mengs U. Assessment of the genotoxic risk from laxative senna products. Environ Mol Mutagen 1997;29(1):1-9.
Laxative senna products and several of their specific components have been submitted to a large number of genetic tests. While most studies gave negative responses, results from some of the studies suggest that components of senna products, particularly emodin and aloe-emodin, have genotoxic activity. Assessment of the genotoxicity profile of these substances, in light of other data from animal and human metabolism or kinetic studies, human clinical trials and rodent carcinogenicity studies do not support concerns that senna laxatives pose a genotoxic risk to humans when consumed under prescribed use conditions.

Brustbauer R, Wenisch C. [Bradycardic atrial fibrillation after drinking herbal tea]. DMW 1997;122(30):930-2. (Ger)
BIOSIS COPYRIGHT: BIOL ABS. History and clinical findings: One day after drinking what she thought to be a tea made from borage leaves a 72-year-old woman developed nausea, vomiting and diarrhoea, later also flickering in her eyes and palpitations. She was in a good general state with a blood pressure of 120/75 mm Hg and an irregular heart rate of 52/min. Physical examination was otherwise unremarkable. She had not been on any medication. Investigations: The usual laboratory tests were normal. The electrocardiogram showed atrial fibrillation with a slow ventricular rate with pauses of up to 1.5 s, intermittently type I and II 2~ AV block, and depressed concave ST segments. The level of digoxin was 3.93 ng/ml, that of digitoxin 133.5 ng/ml. Treatment and course: The patient's symptoms quickly improved under symptomatic treatment. Further questioning suggested that she had probably mistaken foxglove leaves for those of borage when picking them to make a brew. Conclusion: If cardiac arrhythmias have occurred after intake of self-picked herbal leaves one should consider digitalis intoxication resulting from misidentification.

Bruynzeel DP. Bulb dermatitis. Dermatological problems in the flower bulb industries. Contact Dermatitis 1997;37(2):70-7.
The irritant and allergenic properties of the most important flower bulbs are described, as well as the clinical symptoms they cause. The tulip contains the allergen tulipalin A; sensitization and irritation are responsible for the development of tulip fingers. The same clinical picture can be caused by Alliums like the onion and garlic. The narcissus causes lily rash, a dermatitis rarely caused by sensitization. The hyacinth evokes itching in practically everyone: an irritant reaction caused by calcium oxalate crystals. Patch testing is complicated as the allergens are not all identified.

Burnakis TG. It's only natural. Hosp Pharm 1998 Aug;33:1006-7.
IPA COPYRIGHT: ASHP Some adverse effects and drug interactions of alternative medicines are reported, including the development of severe chronic interstitial nephritis in a patient with previously normal renal function after self-medication with chromium picolinate, the occurrence of drug interactions between ginseng and both warfarin and digoxin, and the development of spontaneous bleeding in 2 subjects who had taken Ginkgo biloba.

Caballero T, Martin-Esteban M. Association between pollen hypersensitivity and edible vegetable allergy: A review. J Invest Allergol Clin Immunol 1998;8(1):6-16.
BIOSIS COPYRIGHT: BIOL ABS. Over the last three decades several authors have described the existence of an association between sensitivity to different pollens and sensitivity to diverse edible vegetables. An association between ragweed pollinosis and hypersensitivity to Cucurbitaceae vegetables (e.g., watermelon, melon, cucumber) and banana has been reported. Other authors have found a relationship between birch pollinosis and sensitization to hazelnut, apple, carrot, potato, kiwi and other vegetables. Additionally, several papers have shown the association between mugwort pollinosis and sensitization to celery, carrot, spices, nuts, mustard and Leguminoseae vegetables. Later some studies showed association between grass pollinosis and sensitization to tomato, potato, green-pea, peanut, watermelon, melon, apple, orange and kiwi. Finally, an association between sensitization to plantain pollen and melon hypersensitivity was also described. The association between pollinosis and edible vegetable sensitization has been explained by the combination of different hypotheses, such as the following. 1) presence of lectins in edible vegetables; 2) existence of IgE to carbohydrates of the glycoproteins (crossreactive carbohydrate determinants); and, 3) existence of common allergens between pollens and edible vegetables. Up to now three allergens have been identified as responsible for cross-reactivity in these associations: profilin, a 14 kd protein that regulates actin; Bet v 1, the 18 kd birch pollen allergen; and a 60-69 kd allergen. It is important to study in depth these associated sensitizations and the common allergens responsible for them in order to improve diagnostic methods and treatment of these syndromes.

Calore EE, Cavaliere MJ, Haraguchi M, Gorniak SL, Dagli ML, Raspantini PC, Calore NM, Weg R. Toxic peripheral neuropathy of chicks fed Senna occidentalis seeds. Ecotoxicol Environ Saf 1998;39(1):27-30.
Plants of the genus Senna (formerly Cassia) are poisonous to livestock and other laboratory animals, leading to a syndrome of a widespread muscle degeneration, incoordination, recumbence, and death. The main histologic lesion is necrosis of skeletal muscle fibers. Recently, a mitochondrial myopathy with ragged-red and cytochrome oxidase (COX)-negative muscle fibers was recognized in hens chronically intoxicated with parts of seeds of S. occidentalis. The purpose of the present work was to investigate if there was peripheral nerve involvement in the acute intoxication of chicks with S. occidentalis seeds. Teasing of individual fibers revealed signs of extensive axonal damage with myelin ovoids. Ultrathin sections confirmed the axonal damage. Axons were filled with membranes, some residual disorganized filaments, and enlarged mitochondria. In some instances the axon disappeared and there was secondary degeneration of the myelin sheath. The present work is the first description of the neurotoxic effect of S. occidentalis intoxication. Future work should attempt to determine the mechanisms involved in this neuropathy.

Calore EE, Cavaliere MJ, Haraguchi M, Gorniak SL, Dagli ML, Raspantini PC, Perez Calore NM. Experimental mitochondrial myopathy induced by chronic intoxication by Senna occidentalis seeds. J Neurol Sci 1997;146(1):1-6.
Histochemical and electron microscopic studies of biceps femoris, pectoralis major and rectus femoris of chronically treated birds with seeds of the poisonous plant Senna occidentalis (0.2% external/internal tegment), were performed. The muscles had similar features of human mitochondrial myopathy as ragged-red fibers, cytochrome-oxidase negative fibers, and weak activity of the oxidative enzymes. Fibers with lipid storage were also present. Acid phosphatase activity in rare muscle fibers was also detected, and represents probably a secondary degenerative process. By electron microscopy, enlarged mitochondria with disrupted or excessively branched cristae were seen. The present study presents a new experimental model of mitochondrial myopathy that may be useful for the best knowledge of this group of diseases and for experimental trials of drugs that could reverse the mitochondrial impairment in the mitochondrial myopathies.

Campana MA, Panzeri AM, Moreno VJ, Dulout FN. Genotoxic evaluation of the pyrethroid lambda-cyhalothrin using the micronucleus test in erythrocytes of the fish Cheirodon interruptus interruptus. Mutat Res 1999;438(2):155-61.
In order to develop experimental models able to detect genotoxic effects of pollutants in aquatic organisms, the genotoxicity of the pyrethroid lambda-cyhalothrin was studied using the micronucleus test in erythrocytes of Cheirodon interruptus interruptus. The frequency of micronuclei was examined in blood smears obtained from fishes exposed in vivo to three different concentrations (0.05; 0. 01; 0.001 ug/l) of the compound and sacrificed at nine sampling times (24, 48, 72, 96 h and 8, 12, 15, 19 and 23 days). As a positive control fishes were exposed to 5 mg/l of cyclophosphamide. Results obtained demonstrated the genotoxic effects of the pyrethroid in the experimental model employed. The variation in the micronuclei frequencies in the different sampling times could be related to the blood cell kinetics and the erythrocyte replacement. The results could be considered as a validation of the MN test in fishes for the assessment of genotoxic pollutants. Copyright 1999 Published by Elsevier Science B.V.

Cantor C. Kava and alcohol [letter; comment]. Med J Aust 1997;167(10):560.

Catania PN. Problems with herbal remedies in anticoagulated home care patients. Home Care Provid 1998;3(5):253-5.
The increasing popularity of alternative therapies, including herbal remedies, poses new challenges for home health care providers. The cost of herbal remedy use now exceeds $1 billion annually in the United States and is expected to increase. The use of traditional medicine in combination with alternative therapy may lead to complications for patients and their caregivers as evidenced by the adverse effects of certain herbal products in patients who receive traditional anticoagulant or antiplatelet medication.

Cavaliere MJ, Calore EE, Haraguchi M, Gorniak SL, Dagli ML, Raspantini PC, Calore NM, Weg R. Mitochondrial myopathy in Senna occidentalis-seed-fed chicken. Ecotoxicol Environ Saf 1997;37(2):181-5.
Plants of the genus Senna (formerly Cassia) have been recognized as the cause of a natural and experimental syndrome of muscle degeneration frequently leading to death in animals. Histologically, it demonstrated skeletal and cardiac muscle necrosis, with floccular degeneration and proliferation of sarcolemmal nuclei. Recently, it was described as an experimental model of mitochondrial myopathy in hens chronically treated with Senna occidentalis. Currently, skeletal muscles of chicks intoxicated with seeds of the poisonous plant S. occidentalis were studied by histochemistry and electron microscopy. Since birth, the birds were fed ground dried seeds of this plant with a regular chicken ration at a dose of 4% for 11 days. Microscopic examination revealed, besides muscle-fiber atrophy, lipid storage in most fibers and a moderate amount of cytochrome oxidase-negative fibers. By electron microscopy, enlarged mitochondria with disrupted or excessively branched cristae were seen. This picture was characteristic of mitochondrial myopathy. These findings have hitherto remained unnoticed in skeletal muscle of young birds treated with S. occidentalis.

Ceha LJ, Presperin C, Young E, Allswede M, Erickson T. Anticholinergic toxicity from nightshade berry poisoning responsive to physostigmine. J Emerg Med 1997;15(1):65-9.
The woody nightshade, Solanum dulcamara, belongs to the genus Solanum and its primary toxin is solanine. We report a large nightshade ingestion in a 4-yr-old girl who presented to the emergency department in acute anticholinergic crisis. The child was given 0.2 mg of intravenous physostigmine (0.02 mg/kg). Within 50 min, the patient received two additional equal doses with complete resolution of symptoms. After 36 h of observation, the child was discharged. Our patient presented with symptoms more suggestive of the deadly nightshade species, Atropa belladonna, which is native to Europe; however, a detailed laboratory analysis of the suspect berries revealed no atropine or hyoscyamine. Analysis did reveal sterols consistent with solanine. This is a unique case presentation of woody nightshade, S. dulcamara, poisoning presenting with anticholinergic crisis and responding to physostigmine.

Cerrato PL. Natural tranquilizers? RN Mag 1998 Dec;61:61-2, 68-9.
IPA COPYRIGHT: ASHP A brief overview of the anxiolytic effects of extracts of kava and valerian and the dosage, adverse effects, contraindications, and drug interactions of these preparations is presented.

Chang HL, Kuo ML, Lin JM. Mutagenic activity of incense smoke in comparison to formaldehyde and acetaldehyde in Salmonella typhimurium TA102. Bull Environ Contam Toxicol 1997;58(3):394-401.

Chang IM. Liver-protective activities of aucubin derived from traditional oriental medicine. Res Commun Mol Pathol Pharmacol 1998;102(2):189-204.
The iridoid glycosides including aucubin (AU), catalpol (CA), swertimarin (SW), and gardenoside (GA) are frequently found as natural constituents of many traditional oriental medicinal plants including Chinese herbs. Among these iridoid glycosides, AU was systematically studied for its potent liver-protective activities using experimental systems of hepatic damage. AU showed high liver-protective activity against carbon tetrachloride-induced hepatic damage in mice. Also AU showed significant protective activity against alpha-amanitin-induced hepatic damage in mice, and it prevented a depression of liver RNA biosynthesis caused by alpha-amanitin administration. Potent antidotal effects on mushroom poisoning in beagle dogs ingested with aqueous extract of Amanita virosa was observed; beagle dogs completely survived, even when AU administration was withheld for half an hour after mushroom poisoning. In addition, AU was found to suppress hepatitis B viral DNA replication in vitro. Conversion of AU to its aglycone form appeared to be a prerequisite step for an exhibition of such antiviral activity.

Chang MW, Song GY, Cha HS. [Effect of ginseng extracts on production of vacuolating toxin by Helicobacter pylori]. J Korean Soc Microbiol 1997;32(5):539-51. (Kor)
BIOSIS COPYRIGHT: BIOL ABS. This study was carried out to survey the prevalence of Helicobacter pylori infection and the incidence of vacuolating toxin producing H. pylori from the gastric biopsy specimens of patients with 178 gastritis, 57 gastric ulcer, 455 gastric cancer and 44 healthy person in Pusan, Korea. Further aim of this study was to evaluate the effect of ginseng extract, sofalcone, ginsenosides (F1, Rb3, Re, Rg1), sangwha, green, arrowroot, ginger, and jujube tea on the activity and production of vacuolating toxin by H. pylori in vitro. The isolation rates of H. pylori by culture method from gastric biopsy specimens were 34.1% in healthy person, 42.1% in gastritis, 36.8% in gastric ulcer, and 39.3% in gastric cancer. The isolation rates of vacuolating toxin producing H. pylori from gastric biopsy specimens were 80% in healthy person, 82.7% in gastritis, 81% in gastric ulcer, and 83.8% in gastric cancer. The growth of H. pylori was not influenced by the addition of 10 mug/ml or 100 mug/ml of Ginseng extract and 10 mug/ml of sofalcone in the medium, but the production of vacillating toxin of H. pylori was significantly inhibited by the addition of 100 mug/ml of Ginseng extract and sofalcone. The activity of vacuolating toxin in the culture supernatant of H. pylori was significantly diminished (1/2-1/16 compared to control) by the addition of 10 mg/ml of sangwha, green, arrowroot, and ginger tea, and 1 mug/ml of ginsenosides F1, Rb3, Re, and Rg1. These results suggest that the isolation rates of vacuolating toxin producing H. pylori were significantly higher than that of the foreign reports. Ginseng extract and sofalcone have direct inhibitory effect on the activity of vacuolating toxin production by H. pylori without considerable growth inhibition and sangwha, green, arrowroot, and ginger tea have direct inhibitory effect on the activity of vacuolating toxin of H. pylori.

Chang NY. [Experimental study on the antistimulative and antineoplastic effects of Radix ginseng used in combination with Fafces trogopterus]. J Chin Mater Med 1997;22(11):694-6. (Chi )
IPA COPYRIGHT: ASHP To investigate the effects of Radix ginseng used in combination with Fafces trogopterus, neoplastic mice received R. ginseng either alone or with F. trogopterus. The mice that received the combination demonstrated better antistimulative effects and extended life span than those who received R. ginseng alone.

Chen F, Sun S, Kuhn DC, Lu Y, Gaydos LJ, Shi X, Demers LM. Tetrandrine inhibits signal-induced NF-kappa B activation in rat alveolar macrophages. Biochem Biophys Res Commun 1997;231(1):99-102.
Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from a natural Chinese herbal medicine. While this alkaloid has been shown to exhibit antifibrotic and anti-inflammatory activities, its mechanism of action is unknown. The present study was designed to investigate the inhibitory effect of tetrandrine on NF-kappa B activation in the alveolar macrophage. Three different provocative stimuli were used to activate NF-kappa B in these cells. The results indicate that tetrandrine can inhibit the activation of NF-kappa B and NF-kappa B-dependent reporter gene expression by LPS, PMA, and silica in a dose-dependent manner. In contrast, at the doses used, tetrandrine did not interfere with Sp-1 DNA binding activity or Sp-1-dependent reporter gene expression in these cells. Western blot analysis suggests that the inhibitory effect of tetrandrine on NF-kappa B activation can be attributed to its ability to suppress signal-induced degradation of I kappa B alpha, a cytoplasmic inhibitor of the NF-kappa B transcription factor.

Chen T, Li J, Cao J, Xu Q, Komatsu K, Namba T. A new flavanone isolated from rhizoma smilacis glabrae and the structural requirements of its derivatives for preventing immunological hepatocyte damage. Planta Med 1999;65(1):56-9.
From the rhizome of Smilax glabra Roxb., a new flavanone was isolated and named as smitilbin (1), together with 6 known compounds, engeletin (2), astilbin (3), dihydroquercetin (4), eurryphin (5), resveratrol (6), and 5-O-caffeoylshikimic acid (7). These compounds were applied to the assay of liver nonparenchymal cells (NPC) against hepatocytes (HC) isolated from mice with an immunological liver injury. Against the NPC-caused elevation of ALT (alanine transminase) in culture supernatant from HC, the pretreatment of NPC with flavanoids (1-3) dose-dependently blocked the ALT release while 4, the aglycone of 3, did not. The chromone 5 showed a much stronger inhibition. Compound 6 also showed the activity. However, 1-7 did not show any suppression of NPC or CCl4-induced ALT release when they were used to pretreat HC. These results suggest that compounds 1-3, 5, and 6 could protect the hepatocyte damage from NPC through selectively producing the dysfunction of NPC with an essential requirement of rhamnose, and the chromone part in their structures may be critical for exhibiting the activity rather than through protecting the hepatocyte membranes.

Chen Xiaoliang, Gui Xiaoming, Xie Zhenjia. [Influence of processing methods on alkaloid, toxicity and effect of Strychnos nux-vomica L]. Zhongguo Zhongyao Zazhi 1998;23(3):151-3, 191. (Chi)
BIOSIS COPYRIGHT: BIOL ABS. Determination has been made on the contents of strychnine, brucine and ephedrin in different processed products of Strychnos nux-vomica. The acute toxicity, analgesic and antiphlogistic actions of these products have also been detected. The result shows that the product processed with Ephedra sinica can reduce toxicity and promote 'curative effect. Among the different processing methods the preparation with Ephedra and Liqorice root and the preparation with Ephedra and alcohol appear better and thus useful in practical application.

Cheng KT, Tsay HS, Chen CF, Chou TW. Determination of the components in a Chinese prescription, yu-ping-feng san, by RAPD analysis. Planta Med 1998;64(6):563-5.
In this study, the RAPD (random amplified polymorphic DNA) technique was employed for the first time to determine the components in a Chinese herbal prescription. Forty decamer oligonucleotide primers were screened in the RAPD analysis to identify three Chinese medicines, the dried root of Astragalus membranaceus (Fisch.) Bge., the dried root of Ledebouriella seseloides Wolff, and the dried rhizome of Atractylodes macrocephala Koidz, in a Chinese prescription. Only primer OPP-10 simultaneously generated three distinct markers were each specific to one component. The marker with 200 bp is specific to Astragalus membranaceus; the 440 bp marker is specific to Atractylodes macrocephala; and the remaining marker with 500 bp was present in Ledebouriella seseloides. The presence of the three herbal medicines in the mixed sample, the Chinese prescription, was determined when the primer OPP-10 RAPD reaction was performed. The technique was proved to contribute to the identification of components in the Chinese medicinal preparations.

Cheng TJ, Wong RH, Lin YP, Hwang YH, Horng JJ, Wang JD. Chinese herbal medicine, sibship, and blood lead in children. Occup Environ Med 1998;55(8):573-6.
OBJECTIVES: Risk factors for increased blood lead concentration (BPb) has been investigated. However, the effect of sibship and Chinese herbal medicine on BPb has not been systematically studied. In this study BPb data from voluntary testing was used to determine if Chinese herbal medicine and sibship were associated with BPb. METHODS: 319 children aged 1-7 were tested for BPb. Meanwhile, parents were interviewed to obtain information including consumption of Chinese herbal medicine, living environment, lifestyle, and sibship of the children tested. RESULTS: The mean (SD) BPb of 319 preschool children was 4.4 (2.4) micrograms/dl. The consumption of Ba-baw-san (a Chinese herbal medicine) was significantly associated with increased BPb in children (p = 0.038). Further multivariate regression analysis of BPb in 50 pairs of siblings showed the factors of being brothers explained 75% of variation for BPb, and being sisters and brother-sister explained 51% and 41% of variation respectively. CONCLUSION: Chinese herbal medicine and children's play patterns within the family expressed in different types of sibship are the main determinants of low concentrations of BPb in preschool children of Taiwan.

Cheng TO. Warfarin danshen interaction [letter]. Ann Thorac Surg 1999;67(3):894.

Chou CT, Chang SC. The inhibitory effect of common traditional anti-rheumatic herb formulas on prostaglandin E and interleukin 2 in vitro: a comparative study with Tripterygium wilfordii. J Ethnopharmacol 1998;62(2):167-71.
To understand the clinical efficacy of traditional anti-rheumatic herbal medicines on acute and severe arthritis or immune diseases, four herbal formulas and one herb were tested in vitro to determine their effects on prostaglandin E2 (PGE2) and interleukin 2 (IL2). Peripheral blood mononuclear cells from healthy subjects were incubated with different concentrations of four herbal formulas including Shaur Yau Gan Tsao Tang (SYGTT), Shang Jong Shiah Tong Yong Tong Feng Wan (SJSTY), Shu Jin Lih An Saan (SJLAS), Ma Shing Yih Gan Tang (MSYGT) and one herb, Tripterygium wilfordii (T2) with and without mitogen stimulation. PGE2 and IL2 from culture supernatant were measured by enzyme immunoassay. The results showed that SYGTT, SJSTY, SJLAS at concentration of 100 microg and MSYGT at 500 microg/ml can significantly inhibit PGE2 release (P < 0.05) from mononuclear cells. However, T2 at 2 microg/ml expressed the same response. For the inhibition of IL2, the concentration of SYGTT, SJSTY and SJLAS must exceed 100 symbol microg/ml. MSYGT failed to inhibit IL2 at even concentrations of 500 microg/ml but T2 at a very low concentration (0.6 microg/ml) could strongly inhibit it. The findings suggest that the majority of traditional anti-rheumatic herbal formulas or herbs, except for T2, should not be used to treat acute and critical arthritis or immune diseases.

Chughtai SR, Ahmad MA, Naseem K, Mohmand AS. Genotoxicity testing of some spices in diploid yeast. Pakistan J Botany 1998;30(1):33-8.
BIOSIS COPYRIGHT: BIOL ABS. A study was conducted to assess the mutagenic and recombinogenic potential of 10 commonly consumed spices and condiments viz., bay leaves, black pepper, cardamom small, caraway, red chilies, cinnamon, coriander, fennel, garlic and curry powder in the diploid yeast Saccharomyces cerevisiae. Aqueous extracts of these spices were tested for the induction of mitotic gene conversion and reverse mutation in the diploid strain D7 of the yeast. All except cinnamon failed to induce detectable recombination and mutations in the growing cells of the yeast without exogenous metabolic activation. Treatments with an aqueous extracts of cinnamon significantly increased the rate of gene conversion and reverse mutation. Cinnamon caused cells death and inhibition of cell division. Ethyl methane sulphonate (EMS) used as a positive control exhibited recombinogenic and mutagenic effects.

Church D. Alternative remedies [letter; comment]. N Z Med J 1998;111(1060):59.

Ciordia R. Beware "St. John's Wort," potential herbal danger [letter]. J Clin Monit Comput 1998;14(3):215.

Clark SM, Wilkinson SM. Phototoxic contact dermatitis from 5-methoxypsoralen in aromatherapy oil. Contact Dermatitis 1998;38(5):289-90.
BIOSIS COPYRIGHT: BIOL ABS. RRM CASE STUDY HUMAN PATIENT ADULT FEMALE HUMAN PHOTOTOXIC CONTACT DERMATITIS TOXICITY 5-METHOXYPSORALEN AROMATHERAPY OIL HERBAL REMEDIES PRODUCT INFORMATION TOXICOLOGY DERMATOLOGY ALLERGY INTEGUMENTARY SYSTEM DISEASE.

Cockayne SE, Gawkrodger DJ. Occupational contact dermatitis in an aromatherapist. Contact Dermatitis 1997,37(6):306-7.
A case study of a 32 year old woman who worked as a holistic beauty therapist for 12 years was presented. At presentation she had a 9 month history of patchy eczema on her hands and body. Her condition improved when she was off work. Treatment had included topical corticosteroids and emollients. At work she performed aromatherapy massages and facials with essential oils. Her hobby was gardening and she always wore gloves during this activity. Positive patch test results were noted to nickel-sulfate (12503536), paratertiary-butylphenol-formaldehyde-resin, fragrance mix, lemon-grass-oil (8007021), lavender-absolute (8000280), cananga-oil (83863303), Bulgarian rose-oil (8007010), ylang-ylang (8006813), patchouli (8014093), clary-sage (8016635), her own pedicure foot lotion, and her own facial lotion. Her facial lotion contained hazel-nut-oil, beeswax, avocado-oil, carnuba, basil-oil, tonka-bean absolute, bitter-orange-oil, and chamomile oil. The pedicure foot lotion contained the essential oils of peppermint, black pepper, juniper, eucalyptus and rosemary. No common allergen was found in all of the compounds that gave a positive result. The authors note that patch testing with a perfume series and with the patient's own products was absolutely essential, where aromatherapy is suspected as a source of allergic contact dermatitis.

Combest WL, Nemecz G. Herbal remedies in the pharmacy. US Pharm 1997 Jul;22:50, 52, 55-6, 59.
IPA COPYRIGHT: ASHP An update on herbal remedies used as over-the-counter products in pharmacies is presented, including a discussion of the increase in the use of herbal remedies in the United States, Food and Drug Administration regulations regarding herbal remedies and phytomedicinals, a list of herbs considered unsafe and their potential side effects, quality control and standardization issues regarding herbal remedies, potential dangers of self-treatment with herbal remedies, and information for the pharmacist to prepare them to give advice on herbal remedies to patients.

Cosyns JP, Goebbels RM, Liberton V, Schmeiser HH, Bieler CA, Bernard AM. Chinese herbs nephropathy-associated slimming regimen induces tumours in the forestomach but no interstitial nephropathy in rats. Arch Toxicol 1998;72(11):738-43.
Chinese herbs nephropathy (CHN), a rapidly progressive interstitial fibrosis of the kidney, has been described in approximately 100 young Belgian women who had followed a slimming regimen containing some Chinese herbs. In 4 patients multifocal transitional cell carcinomas (TCC) were observed. Aristolochic acid (AA), suspected as the causal factor of CHN, is a well known carcinogen but its ability to induce fibrosis has never been demonstrated. The objective of this study was to evaluate the latter using doses of AA, durations of intoxication and delays of sacrifice known to yield tumours in rats. We also tested the hypothesis that a possible fibrogenic role of AA was enhanced by the other components of the slimming regimen. Male and female rats were treated orally with 10 mg isolated AA/kg per day for 5 days/week, or with approximately 0.15 mg AA/ kg per day 5 days/week contained in the herbal powder together with the other components prescribed in the slimming pills for 3 months. The animals were killed respectively 3 and 11 months later. At sacrifice, animals in both groups had developed the expected tumours but not fibrosis of the renal interstitium. Whether the fibrotic response observed in man is due to species and/or strain related differences in the response to AA or to other factors, remains to be determined. Interestingly, despite the addition of fenfluramine and diethylpropion, two drugs incriminated in the development of valvular heart disease, no cardiac abnormalities were observed.

Cosyns JP, Jadoul M, Squifflet JP, Wese FX, Van Ypersele De Strihou C. Urothelial lesions in Chinese-herb nephropathy [see comments]. Am J Kidney Dis 1999;33(6):1011-7.
Rapidly progressive renal fibrosis after a slimming regimen including Chinese herbs containing aristolochic acid (AA) has been identified as Chinese-herb nephropathy (CHN). We reported urothelial atypia in three patients with CHN, with the subsequent development in one patient of overt transitional cell carcinoma (TCC). Therefore, it was decided to remove the native kidneys, as well as the ureters, in all patients with CHN. Nineteen kidneys and ureters removed during and/or after renal transplantation from 10 patients were studied to assess critically urothelial lesions and to characterize the cellular expression of p53, a tumor-suppressor gene overexpressed in several types of malignancies. Multifocal high-grade flat TCC in situ (carcinoma in situ; CiS) was observed, mainly in the upper urinary tract, in four patients, a prevalence of 40%. In one of those patients, a superficially invasive flat TCC of the right upper ureter, as well as two additional foci of noninvasive papillary TCC, were found in the right pelvis and left lower ureter, respectively. This patient also presented recurrent noninvasive papillary TCC of the bladder. Furthermore, in all cases, multifocal, overall moderate atypia was found in the medullary collecting ducts, pelvis, and ureter. All CiS and papillary TCC, as well as urothelial atypia, overexpressed p53. These results show that the intake of Chinese herbs containing AA has a dramatic carcinogenic effect. Carcinogenesis is associated with the overexpression of p53, which suggests a role for a p53 gene mutation. The relationship of this mutation with the reported presence of AA DNA adducts in the kidney remains to be explored.

Crone CC, Wise TN. Survey of alternative medicine use among organ transplant patients. J Transpl Coord 1997;7(3):123-30.
Herbal medicine and health food supplements have become increasingly popular. However, many of these pharmacologically active compounds remain poorly understood. Patients with chronic and life-threatening conditions often use alternative therapies while receiving conventional medical care, and his population is at increased risk for complications and adverse drug interactions due to poor health and complex drug regimens. Patients awaiting or who had received solid organ transplants were surveyed about their use of herbal medicines and health food supplements. Twenty percent of respondents acknowledged experience with these products, which they used to prolong the function of a failing organ or to obtain relief from fatigue and insomnia. Transplant staff often were unaware of their patients' use of these treatments, despite patients' claims to the contrary. The potential for unexpected drug interactions, toxicity, and other adverse reactions resulting from the use of herbal medicines or supplements must be recognized and identified by transplant teams.

Cutler SJ, Cutler HG. Natural central nervous system agents. US Pharm 1997 Nov;22:87-8, 90, 93-4.

De Boer D, Egberts T, Maes RA. Para-methylthioamphetamine, a new amphetamine designer drug of abuse. Pharm World Sci 1999;21(1):47-8.
A case study is described of a patient who was intoxicated after the intake of so-called herbal stimulants. A visit to a physician after the intoxication prompted to this investigation and the case was examined for its direct cause. An interview with the patient revealed that the source of the herbal stimulants was a so-called 'S-5 tablet'. Information provided on the packings of the tablet only indicated the presence of natural alkaloids and vitamins. Toxicological analysis however proved that the 'S-5 tablet' contained para-methylthioamphetamine (MTA), mainly. MTA is a relative unknown amphetamine designer drug, which has only been studied as a model compound in some structure-activity relationship studies. The fact that MTA appeared in tablets was therefore completely unexpected. Not only the potential abuse of this new amphetamine designer drug is a serious matter of concern, but also the misleading information provided with the tablet.

De Broe ME. On a nephrotoxic and carcinogenic slimming regimen [editorial; comment]. Am J Kidney Dis 1999;33(6):1171-3.

De Broe ME, et al . Clinical nephrotoxins: renal injury from drugs and chemicals. Dordrecht(Netherlands), Norwell(MA): Kluwer Academic Publishers; 1998. 481 P.
BIOSIS COPYRIGHT: BIOL ABS. RRM BOOK ANIMAL HUMAN ANIMAL MODEL NEPHROTOXICITY ENVIRONMENTAL TOXINS TOXIN PHARMACEUTICAL AGENTS XENOBIOTICS RENAL DYSFUNCTION RENAL INJURY KIDNEY ANTI-INFECTIOUS AGENTS ANALGESICS IMMUNOSUPPRESSIVE DRUGS HERBAL REMEDIES ADVERSE RENAL EFFECTS URINARY SYSTEM CELL CULTURE MODEL TOXICOLOGY UROLOGIC DISEASE EXCRETORY SYSTEM.

De Soriano G, Chase D. Safety of herbal remedies [letter]. J R Soc Med 1998;91(10):561.

Deng JF, Lin TJ, Kao WF, Chen SS. The difficulty in handling poisonings associated with Chinese traditional medicine: a poison control center experience for 1991-1993. Vet Hum Toxicol 1997;39(2):106-14.
The purpose of this prospective case series was to outline the characteristics of Chinese traditional medicine poisonings and develop essential information for poison prevention and management. All phone inquiries made to the Poison Center related to Chinese traditional medicines from January 1, 1991 to December 31, 1993 were included. Standardized questionnaires were used to capture relevant information. Among the 318 phone inquiries about Chinese traditional medicines, 273 cases were classified as poisonings; and 22 mortalities occurred (6.9%). All of the poisonings occurred because of suicide attempts, accidents, or erroneous or improper use or processing. In our study, 47% of the potential toxic effects of Chinese traditional medicines were either unknown or could not be found in the literature. There existed undefinable uncertainty in attributing the clinical effects to the exposures to Chinese traditional medicines. We recommend that the strategy in handling Chinese traditional medicine poisonings to decrease mortality should be comprised of confirmation of the generic name of the substances and the specific part of the plant used, awareness of improper processing methods, maintenance of records on a broad review of systems and laboratory data, identification of active principles and potential interactions among the individual active agents; verification of histopathologic effects of the toxins; development of information on toxicodynamics and toxicokinetics; intensive supportive care for poisoned patients, and investigation of potential antidotes. There are several regulatory options available to health authorities to control the unrestricted use of these potentially toxic medicines and to help safeguard the public.

Dewitt MS, Swain R, Gibson LB Jr. The dangers of jimson weed and its abuse by teenagers in the Kanawha Valley of West Virginia. W V Med J 1997;93(4):182-5.
Jimson weed (Datura stramonium, a member of the Belladonna alkyloid family) is a plant growing naturally in West Virginia and has been used as a home remedy since colonial times. Due to its easy availability and strong anticholinergic properties, teens are using Jimson weed as a drug. Plant parts can be brewed as a tea or chewed, and seed pods, commonly known as "pods" or "thorn apples," can be eaten. Side effects from ingesting jimson weed include tachycardia, dry mouth, dilated pupils, blurred vision, ballucinations, confusion, combative behavior, and difficulty urinating. Severe toxicity has been associated with coma and seizures, although death is rare. Treatment consists of activated charcoal and gastric lavage. Esmolol or other beta-blocker may be indicated to reduce severe sinus tachycardia. Seizures, severe hypertension, severe hallucinations, and life-threatening arrhythmias are indicators for the use of the anticholinesterase inhibitor, Physostigmine. This article reviews the cases of nine teenagers who were treated in hospitals in the Kanawha Valley after ingesting jimson weed. We hope this article will help alert primary care physicians about the abuse of jimson weed and inform health officials about the need to educate teens about the dangers of this plant.

Dipaola RS, Zhang H, Lambert GH, Meeker R, Licitra E, Rafi MM, Zhu BT, Spaulding H, Goodin S, Toledano MB, et al. Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer [see comments]. N Engl J Med 1998;339(12):785-91.
BACKGROUND: Herbal mixtures are popular alternatives to demonstrated therapies. PC-SPES, a commercially available combination of eight herbs, is used as a nonestrogenic treatment for cancer of the prostate. Since other herbal medicines have estrogenic effects in vitro, we tested the estrogenic activity of PC-SPES in yeast and mice and in men with prostate cancer. METHODS: We measured the estrogenic activity of PC-SPES with transcriptional-activation assays in yeast and a biologic assay in mice. We assessed the clinical activity of PC-SPES in eight patients with hormone-sensitive prostate cancer by measuring serum prostate-specific antigen and testosterone concentrations during and after treatment. RESULTS: In complementary yeast assays, a 1:200 dilution of an ethanol extract of PC-SPES had estrogenic activity similar to that of 1 nM estradiol, and in ovariectomized CD-1 mice, the herbal mixture increased uterine weights substantially. In six of six men with prostate cancer, PC-SPES decreased serum testosterone concentrations (P<0.05), and in eight of eight patients it decreased serum concentrations of prostate-specific antigen. All eight patients had breast tenderness and loss of libido, and one had venous thrombosis. High-performance liquid chromatography, gas chromatography, and mass spectrometry showed that PC-SPES contains estrogenic organic compounds that are distinct from diethylstilbestrol, estrone, and estradiol. CONCLUSIONS: PC-SPES has potent estrogenic activity. The use of this unregulated mixture of herbs may confound the results of standard or experimental therapies and may produce clinically significant adverse effects.

Drew AK, Myers SP. Safety issues in herbal medicine: implications for the health professions [see comments]. Med J Aust 1997;166(10):538-41.
The use of herbal medicines in Australia is widespread. A number of factors make assessment of adverse effects associated with these products more complex than for pharmaceuticals. Problems have resulted from contamination with heavy metals and adulteration with prescription drugs in overseas herbal products. A classification is proposed for adverse effects associated with herbal medicines, and medical practitioners are encouraged to include use of these preparations in a patient's drug history and in reports of suspected adverse drug reactions. It may be necessary to develop a separate database to promote adverse drug reaction reporting for herbal medicine and the wider field of complementary and alternative medicine.

Emmanuel NP, Jones C, Lydiard RB. Use of herbal products and symptoms of bipolar disorder [letter]. Am J Psychiatry 1998;155(11):1627.

Ernst E. Harmless herbs? A review of the recent literature. Am J Med 1998;104(2):170-8.
Herbal medicines have become a popular form of therapy. They are often perceived as being natural and therefore harmless. This article reviews the recent literature on the adverse effects of herbal remedies. Examples of allergic reactions, toxic reactions, adverse effects related to an herb's desired pharmacological actions, possible mutagenic effects, drug interactions, drug contamination, and mistaken plant identities are provided. Because of underreporting, our present knowledge may well be just the "tip of the iceberg." Little is known about the relative safety of herbal remedies compared to synthetic drug treatments, although for some herbal remedies, the risks may be less than for conventional drugs.

Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol 1998;54(8):589-94.
This paper provides a systematic review of adverse drug reactions (ADRs) associated with the use of extracts of the herb St. John's wort (Hypericum perfbratum L.) for the treatment of mild to moderate depression. METHODS: Searches of four computerized literature databases were performed for records of (ADRs). Manufacturers of hypericum products, the international drug monitoring centre of the World Health Organization (WHO) and the national drug safety monitoring bodies of Germany and the United Kingdom were also contacted for information. RESULTS: Information on (ADRs) originates from case reports, clinical trials, post-marketing surveillance and drug monitoring studies. Collectively, the data suggest that hypericum is well tolerated, with an incidence of adverse reactions similar to that of placebo. The most common adverse effects are gastrointestinal symptoms, dizziness/confusion and tiredness/sedation. A potential serious adverse effect is photosensitivity, but this appears to occur extremely rarely. CONCLUSIONS: Hypericum has an encouraging safety profile. However, as most of the current data originate from short-term investigations, more long-term studies are desirable.

Farrell GC. Drug-induced hepatic injury. J Gastroenterol Hepatol 1997;12(9-10):242-50.
Drugs and other chemical toxins account for less than 5% of cases of jaundice or acute hepatitis and fewer cases of chronic liver disease, but they are an important cause of more severe types of hepatic injury. Drug reactions produce an array of hepatic lesions that mimic all known hepatobiliary diseases; this poses a diagnostic challenge for physicians and pathologists. Diagnosis of drug-induced hepatic injury is circumstantial, with positive rechallenge being the only factor that unequivocally implicates a particular agent. Nonetheless, other aspects of the temporal relationship between drug ingestion and adverse reaction, exclusion of other diseases, the presence of extrahepatic features of drug hypersensitivity and some findings on liver biopsy can lend support to the diagnosis. Some of these issues will be explored in this review by considering contemporary paradigms of drug-induced hepatic injury. Factors that predispose to dose-dependent hepatic injury will be considered in relation to acetaminophen, an example of acute hepatotoxicity, and methotrexate, an agent that can produce hepatic fibrosis. Flucloxacillin will be discussed as an example of drug-induced cholestatic hepatitis often associated with prolonged cholestasis and the vanishing bile duct syndrome. Minocycline and diclofenac will be mentioned as two drugs for which drug hepatitis is an exceedingly rare complication. Finally, the evidence that Chinese herbal medicines can be hepatotoxic will be reviewed.

Fau D, Lekehal M, Farrell G, Moreau A, Moulis C, Feldmann G, Haouzi D, Pessayre D. Diterpenoids from germander, an herbal medicine, induce apoptosis in isolated rat hepatocytes [see comments]. Gastroenterology 1997;113(4):1334-46.
BACKGROUND & AIMS: Germander was withdrawn from the market after its use for weight control caused an epidemic of hepatitis. Its toxicity was shown to be caused by diterpenoids and their cytochrome P4503A-mediated metabolic activation into electrophilic metabolites that deplete cellular thiols. The aim of the present study was to determine the mechanisms of cell death. METHODS: Isolated rat hepatocytes were incubated for 2 hours with germander diterpenoids (100 micrograms/mL). RESULTS: Diterpenoids decreased cell glutathione, increased cytosolic [Ca2+], activated Ca(2+)-dependent tissue transglutaminase forming a cross-linked protein scaffold, and caused internucleosomal DNA fragmentation and the ultrastructural features of apoptosis. Cell death was prevented by decreasing metabolic activation (with troleandomycin), preventing depletion of glutathione (with cystine), blocking activation of Ca(2+)-modulated enzymes (with calmidazolium), or inhibiting internucleosomal DNA fragmentation (with aurintricarboxylic acid). Apoptosis was increased and diterpenoids caused overexpression of p53 and interleukin 1 beta-converting enzyme in rats treated with dexamethasone (cytochrome P4503A inducer). Apoptosis was also increased by a diet deficient in sulfur amino acids. CONCLUSIONS: The germander furano diterpenoids cause apoptosis within 2 hours in isolated rat hepatocytes. Electrophilic metabolites may stimulate apoptosis by decreasing thiols, increasing [Ca2+], and activating Ca(2+)-dependent transglutaminase and endonucleases.

Ferguson JE, Chalmers RJ, Rowlands DJ. Reversible dilated cardiomyopathy following treatment of atopic eczema with Chinese herbal medicine. Br J Dermatol 1997;136(4):592-3.
Chinese herbal medicines are increasingly being used as an alternative treatment for chronic skin disease. Most patients and many doctors remain insufficiently aware of their potential toxicity. We report a patient with eczema who developed a severe cardiomyopathy following a 2-week course of Chinese herbal medicine. The connection between the two conditions was not made until 2 weeks after presentation when the patient was specifically asked if she had ingested any unusual substances. The belief that herbs, as natural products available without prescription, are harmless, is commonplace and patients may not consider them worthy of mention during a standard medical history.

Fernandez L, Duque S, Sanchez I, Quinones D, Rodriguez F, Garcia-Abujeta JL. Allergic contact dermatitis from rosemary (Rosmarinus officinalis L.). Contact Dermatitis 1997;37(5):248-9.
BIOSIS COPYRIGHT: BIOL ABS. RRM CASE STUDY NOTE ROSMARINUS-OFFICINALIS HUMAN PLANT MALE HUMAN MIDDLE AGE DERMATOLOGY HEALTH PHARMACOGNOSY ROSEMARY LEAF PLASTER ANTIINFLAMMATORY HERBAL REMEDY ALLERGIC CONTACT DERMATITIS ALLERGY INTEGUMENTARY SYSTEM DISEASE IMMUNE SYSTEM DISEASE.

Figueiredo MR, Kaplan MA. Pyrrolizidine alkaloids: a word of caution. Cienc Cultur 1997;49(5-6):331-8.
BIOSIS COPYRIGHT: BIOL ABS. Most plants bearing pyrrolizidine alkaloids (PAs) are toxic to men and animals. These natural products are recognized to be hepatotoxic, pneumotoxic, carcinogenic and mutagenic. Thus, the presence of toxic pyrrolizidine alkaloids in certain medicinal plants entails a serious health risk. Moreover, people are exposed to undetermined toxicity hazards of pyrrolizidine alkaloid-containing plants due to the consumption of milk and meat from chronically PA-poisoned animals and honey from wild bees. Symphytum officinale (comfrey) has been used freely as tea, topical cream, salad and beverage. This is a clear and actual example of how lack of knowledge about chemistry and toxicology of a plant made easy its spreading in the consumer society as beneficial and safe.

Fox C. Technically speaking. Cosmet Toiletries 1998 Sep;113:29-32.
IPA COPYRIGHT: ASHP An overview of current discoveries related to cosmetic products is presented, including a discussion of the role of essential fatty acids in maintaining skin function, herbal irritations related to creams prescribed by Chinese herbalists, the incidence of lanolin allergies among high-risk populations, moisturizers, silicone elastomers, and conditioners for hair care, and new emulsions and antiperspirant products.

Frasca T, Brett AS, Yoo SD. Mandrake toxicity. A case of mistaken identity. Arch Intern Med 1997;157(17):2007-9.
A 31-year-old man ingested an unknown amount of mandrake plant purchased at a local health food store and came to the emergency department with severe nausea and vomiting. He was hospitalized overnight but recovered uneventfully without obvious adverse systemic effects. This plant was almost certainly Podophyllum peltatum based on chromatographic identification of podophyllotoxin in a sample. However, the patient had mistakenly believed he was taking the anticholinergic and hallucinatory plant Mandragora officinarum, which is also known as mandrake. Other users of herbal substances and authors of the medical literature have also confused these 2 versions of mandrake. Given the growing popularity of alternative therapies, physicians should understand the distinction between these substances and should be aware of the medical effects of other commonly used herbal remedies.

Friede M, Hasenfuss I, Wustenberg P. [Traffic- and work-safety under the effect of St. Johns Wort]. Fortschr Med 1998;116(34):44-5. (Ger)

Friese J, Gleitz J, Gutser UT, Heubach JF, Matthiesen T, Wilffert B, Selve N. Aconitum sp. alkaloids: the modulation of voltage-dependent Na+ channels, toxicity and antinociceptive properties. Eur J Pharmacol 1997;337(2-3):165-74.
Alkaloids from Aconitum sp., used as analgesics in traditional Chinese medicine, were investigated to elucidate their antinociceptive and toxic properties considering: (1) binding to Na+ channel epitope site 2, (2) alterations in synaptosomal Na+ and Ca2+ concentration ([Na+]i, [Ca2+]i), (3) arrhythmogenic action of isolated atria, (4) antinociceptive and (5) acute toxic action in mice. The study revealed a high affinity group (Ki 1 microM) and a low affinity group (Ki 10 microM) of alkaloids binding to site 2. The compounds of the high affinity group induce an increase in synaptosomal [Na+]i and [Ca2+]i (EC50 3 microM), are antinociceptive (ED50, 25 microg/kg), provoke tachyarrhythmia and are highly toxic (LD50 70 microg/kg), whereas low affinity alkaloids reduce [Ca2+]i, induce bradycardia and are less antinociceptive (ED50 20 mg/kg) and less toxic (LD50 30 mg/kg). These results suggest that the alkaloids can be grouped in Na+ channel activating and blocking compounds, but none of the alkaloids seem to be suitable as analgesics because of the low LD50/ED50 values.

Garcia-Bravo B, Bernal AP, Garcia-Hernandez MJ, Camacho F. Occupational contact dermatitis from anethole in food handlers.Contact Dermatitis 1997;37(1):38.
Two case reports of food handlers developing occupational contact dermatitis from anethole (104461) were presented. In the first case, a 39 year old woman who cooked Seville cakes had exhibited a hand dermatitis that was resistant to treatment for 20 years. Upon entering the workplace, the lesions spread up the forearms and rhinitis and blepharitis developed. Standard series patch tests were conducted. The patient reacted positively to anise-oil (8007703) and anethole, the main ingredient in anise-oil, at 2 and 4 days. In the second case, a 38 year old woman who worked in the same cake factory had severe dermatitis on her hands, forearms, scalp, and face. Upon entering the workplace, rhinitis and blepharitis developed. Standard series patch tests were performed. The patient exhibited positive reactions to Kathon-CG (55965849), anise-oil, anethole, and Roman-chamomile at 2 and 4 days. The authors conclude that these cases may be the first reports of occupational contact dermatitis from anethole in food handlers.

Garges HP, Varia I, Doraiswamy PM. Cardiac complications and delirium associated with valerian root withdrawal [letter]. JAMA 1998;280(18):1566-7.

Gianni L, Dreitlein WB. Some popular OTC herbals can interact with anticoagulant therapy. US Pharm 1998 May 23;23:80, 83-4, 86.
IPA COPYRIGHT: ASHP The interaction of Ginkgo biloba, Tanacetum parthenium (feverfew), Allium sativum (garlic), Zingiber officinale (ginger), and vitamin E with anticoagulant therapy and a resulting increase in the risk of bleeding in some patients are discussed.

Giavina-Bianchi PF Jr, Castro FF, Machado ML, Duarte AJ. Occupational respiratory allergic disease induced by Passiflora alata and Rhamnus purshiana. Ann Allergy Asthma Immunol 1997;79(5):449-54.
BACKGROUND: There has been an increase in the incidence of occupational asthma along with better understanding of its pathophysiologic mechanisms and etiologic factors. There are no reports of patients with asthma and rhinitis to Passiflora alata (passion flower) and Rhamnus purshiana (cascara sagrada). METHODS: We describe two substances of plant origin as causal agents of occupational allergic respiratory diseases in a patient who worked in a pharmacy devoted to the manual preparation of products. RESULTS: Skin testing and Western blot confirmed the sensitization of the patient to these plant extracts in vivo and in vitro, respectively. Bronchial challenge confirmed the cause-effect relationship between the allergen exposure and the diseases. CONCLUSIONS: We conclude that Passiflora and cascara sagrada are two new etiologic agents of IgE-mediated occupational asthma and rhinitis. The present study also serves to alert physicians to the risks associated with work in pharmacies devoted to manual preparation of plant extracts, emphasizing the importance of the use of protective measures in these environments.

Goday Bujan JJ, Oleaga Morante JM, Yanguas Bayona I, Gonzalez Guemes M, Soloeta Arechavala R. Allergic contact dermatitis from krameria triandra extract. Contact Dermatitis 1998;38(2):120-1.

Goh CL. The need for epidemiological studies [editorial; comment]. Am J Contact Dermat 1997;8(3):135-6.

Gordon JB. SSRIs and St.John's Wort: possible toxicity? [letter]. Am Fam Physician 1998;57(5):950,953.

Greenberger P. News from the Society for the Advancement of Women's Health Research. Herbal medicines: are supplements safe? [news]. J Womens Health 1998;7(9):1077-9.

Gulick RM, Mcauliffe V, Holden-Wiltse J, Crumpacker C, Liebes L, Stein DS, Meehan P, Hussey S, Forcht J, Valentine FT. Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med 1999;130(6):510-4.
BACKGROUND: Hypericin, the active compound in St. John's Wort, has antiretroviral activity in vitro. Many HIV-infected persons use St. John's wort. OBJECTIVE: To evaluate the safety and antiretroviral activity of hypericin in HIV-infected patients. DESIGN: Phase I study. SETTING: Four clinical research units. PATIENTS: 30 HIV-infected patients with CD4 counts less than 350 cells/mm3. INTERVENTION: Intravenous hypericin, 0.25 or 0.5 mg/kg of body weight twice weekly or 0.25 mg/kg three times weekly, or oral hypericin, 0.5 mg/kg daily. MEASUREMENTS: Safety was assessed at weekly visits. Antiretroviral activity was assessed by changes in HIV p24 antigen level, HIV titer, HIV RNA copies, and CD4 cell counts. RESULTS: Of the 30 patients who were enrolled, 16 discontinued treatment early because of toxic effects. Severe cutaneous phototoxicity was observed in 11 of 23 (48% [95% CI, 27% to 69%]) evaluable patients, and dose escalation could not be completed. Virologic markers and CD4 cell count did not significantly change. CONCLUSIONS: Hypericin caused significant phototoxicity and had no antiretroviral activity in the limited number of patients studied.

Gurley BJ, Gardner SF, White LM, Wang PL. Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica (ma huang). Ther Drug Monit 1998;20(4):439-45.
Nutritional supplements containing Ephedra sinica (ma huang), a botanical source of ephedrine alkaloids, have been linked to several episodes of ephedrine toxicity and at least 17 deaths, yet these products remain unregulated. Ten subjects were enrolled in a randomized, crossover study aimed at characterizing the pharmacokinetics of ephedrine after the ingestion of three commercially available ma huang products compared with a 25-mg ephedrine capsule. Pharmacokinetic parameters for botanical ephedrine were similar to those for synthetic ephedrine hydrochloride. Gender-based comparisons of Vss/F and CL/F revealed higher values for women than for men (Vss/F, 3.49 +/- 1.04 vs 2.98 +/- 0.73 l/kg; CL/F, 0.48 +/- 0.11 vs 0.37 +/- 0.11 l/hour x kg). The current study suggests that the increased incidence of ma huang toxicity does not stem from differences in the absorption of botanical ephedrine compared with synthetic ephedrine; rather, it results from accidental overdose often prompted by exaggerated off-label claims and a belief that "natural" medicinal agents are inherently safe.

Hagemann TM. Gastrointestinal medications and breastfeeding. J Hum Lact 1998;14(3):259-62.
Medications used to treat gastrointestinal symptoms are increasingly being used as more have been gained nonprescription status. Most of the gastrointestinal medications, such as laxatives, antacids, and antidiarrheal agents, are used short term. Women who breastfeed should be aware of the risks of taking any medications, whether prescription or nonprescription. There is little information describing transfer into breast milk for many of these products. Cimetidine, atropine, cascara, cisapride, loperamide, magnesium sulfate, and senna are the only products identified by the AAP as compatible with breast feeding. Metoclopramide is listed by the AAP as a drug whose effect on nursing infants is unknown but may be of potential concern, although studies published to date have not reported any adverse effects. The safest laxatives and antidiarrheals are those that are not absorbed and should be considered first-line therapy for conditions of constipation or loose stools. Famotidine and nizatidine are excreted into breast milk to a lesser extent than cimetidine or ranitidine and may be the preferred histamine antagonists. Despite the limited data on the use of cisapride in nursing women, it is considered safe by the AAP and may be preferred over metoclopramide for first-line prescription treatment of heartburn. Although most of these agents appear safe in the nursing infant, caretakers should be aware of the potential adverse reactions that may occur in infants whose mothers require these products.

Hamid S, Rojter S, Vierling J. Protracted cholestatic hepatitis after the use of prostata [letter]. Ann Intern Med 1997;127(2):169-70.

Haraguchi M, Calore EE, Dagli ML, Cavaliere MJ, Calore NM, Weg R, Raspantini PC, Gorniak SL. Muscle atrophy induced in broiler chicks by parts of Senna occidentalis seeds. Vet Res Commun 1998;22(4):265-71.
Senna occidentalis (formerly Cassia occidentalis) is a common contaminant of agricultural commodities. It is toxic to cattle and poultry, reportedly being responsible for skeletal myodegeneration in these animals. All parts of the plant present toxicity, but the seeds are the most toxic. The toxin(s) responsible for the myodegeneration have not been definitively identified, nor is it known which part of the seeds is most toxic. Intoxication by this plant leads to weight loss with considerable economic repercussions. The effects of the whole seed and of parts of S. occidentalis seeds (1% in commercial feed) were compared on the pectoralis major muscle of broiler chicks intoxicated from birth until 22 days of life. There were severe clinical signals and reduced body weight in birds that received the external tegment of the seed, whereas no adverse effects were observed in birds that received the whole seed or other parts of the seed. Histological and morphometric studies showed an intense muscle fibre atrophy (both type 1 and type 2 fibres were affected) in the group that received 1% external tegment. This study may be the first step to identifying the substance(s) involved in this pathological process.

Haraguchi M, Gorniak SL, Calore EE, Cavaliere MJ, Raspantini PC, Calore NM, Dagli ML. Muscle degeneration in chicks caused by Senna occidentalis seeds. Avian Pathol 1998;27(4):346-51.
BIOSIS COPYRIGHT: BIOL ABS. Acute intoxication with Senna occidentalis seeds was studied in chicks. Seven-day-old chicks were fed ground dried seeds of this plant mixed with regular chicken ration at a concentration of 4% by weight for 15 days. Feed intake and body weight were markedly affected and a high level of lethality was observed. Necropsy examination of chicks from the experimental group revealed paleness and atrophy of thoracic muscles. Degenerative and necrotic fibres were observed in skeletal muscle by histological examination. Muscle histochemistry showed accumulation of lipids and numerous acid phosphatase-positive muscle fibres. Electron microscopy revealed atrophic muscle fibres, lipid storage, dilatation of the sarcoplasmic reticulum and abnormal mitochondria.

Hasegawa S, Nakayama K, Iwakiri K, An E, Gomi S, Dan K, Katsumata M, Minami M, Wakabayashi I. Herbal medicine-associated lead intoxication. Intern Med 1997;36(1):56-8.
A female patient visited our hospital with abdominal pain and anemia. Examination for a gastrointestinal disease gave no diagnostic information. Laboratory studies of the parameters of heme biosynthesis revealed an enzymatic inhibition by lead. The diagnosis of lead poisoning was confirmed by detection of an elevated blood lead level. Excessive lead ingestion was thought to be caused by herbal medicines and/or by an earthen teapot.

Hata M, Sasaki E, Ota M, Fujimoto K, Yajima J, Shichida T, Honda M. Allergic contact dermatitis from curcumin (turmeric). Contact Dermatitis 1997;36(2):107-8.

Heki U, Fujimura M, Ogawa H, Matsuda T, Kitagawa M. Pneumonitis caused by saikokeisikankyou-tou, an herbal drug. Intern Med 1997;36(3):214-7.
A 57-year-old man was admitted to our hospital because of dyspnea and abnormal shadow on chest roentgenogram. He had received two herbal drugs: Saikokeisikankyou-tou (SKT) for one month and Licium Halimifolium Mil (LHM) for two weeks. After admission, all medication was stopped and his symptoms were gradually diminished. Transbronchial lung biopsy specimens showed interstitial pneumonia. Lymphocyte stimulation test, skin test and challenge test were positive to these herbal drugs. We diagnosed him as drug-induced pneumonitis. This is the first report on pneumonitis caused by Saikokeisikankyou-tou diagnosed by lymphocyte stimulation test, skin test and challenge test.

Higenbottam TW. Bronchiolitis obliterans following the ingestion of an Asian shrub leaf. Thorax 1997;52(Suppl 3):68-72.

Hilepo JN, Bellucci AG, Mossey RT. Acute renal failure caused by 'cat's claw' herbal remedy in a patient with systemic lupus erythematosus [letter]. Nephron 1997;77(3):361.

Hofman M, Diaz JE, Martella C. Oil of wintergreen overdose [letter]. Ann Emerg Med 1998;31(6):793-4.

Holland EG, Degruy FV. Drug-induced disorders [see comments]. Am Fam Physician 1997;56(7):1781-8, 1791-2.
Recent estimates suggest that each year more than 1 million patients are injured while in the hospital and approximately 180,000 die because of these injuries. Furthermore, drug-related morbidity and mortality are common and are estimated to cost more than $136 billion a year. The most common type of drug-induced disorder is dose-dependent and predictable. Many adverse drug events occur as a result of drug-drug, drug-disease or drug-food interactions and, therefore, are preventable. Clinicians' awareness of the agents that commonly cause drug-induced disorders and recognition of compromised organ function can significantly decrease the likelihood that an adverse event will occur. Patient assessment should include a thorough medication history, including an analysis of all prescribed and over-the-counter medications, vitamins, herbs and "health-food" products to identify drug-induced problems and potentially reversible conditions. An increased awareness among clinicians of drug-induced disorders should maximize their recognition and minimize their incidence.

Hsu HY, Lin CC, Chen JY, Yang JJ, Zhang R. Toxic effects of Erycibe obtusifolia, a Chinese medicinal herb, in mice. J Ethnopharmacol 1998;62(2):101-5.
Extract of stem of Erycibe obtusifolia (EO) at doses of 10, 20 and 30 mg/kg was experimentally tested through oral and intraperitoneal administration. Toxic effects of EO were assessed through functional changes of the liver and kidneys. Mice died immediately following the i.p. injection at the dose of 10 mg/kg. However, no death occurred after the oral administration at the dose of 10, 20 or 30 mg/kg under close observations for at least 2 weeks. Changes of several functional parameters in both the liver and kidney appeared simultaneously after the oral administration. Although the higher dose increased the levels of serum glutamate-oxalate-transaminase (sGOT), serum glutamate-pyruvate-transaminase (sGPT), and blood urea nitrogen (BUN), and decreased the levels of hematocrit at 6 h after the treatment, no distinct dose-dependent relationship existed between the administered doses and the changes in functional parameters observed.

Hullar TE, Sapers BL, Ridker PM, Jenkins RL, Huth TS, Farraye FA. Herbal toxicity and fatal hepatic failure [letter]. Am J Med 1999;106(2):267-8.

Hung OL, Shih RD, Chiang WK, Nelson LS, Hoffman RS, Goldfrank LR. Herbal preparation use among urban emergency department patients. Acad Emerg Med 1997;4(3):209-13.
OBJECTIVE: To determine the prevalence of herbal preparation use among patients presenting to an urban teaching hospital ED. METHODS: A prospective anonymous survey on herbal preparation use was performed. Consecutive, acutely ill or injured adult (> or = 18 years old) ED patients were offered the survey over a 1-month period. The survey also asked for information related to patient age, ethnicity, gender, employment, education, cigarette smoking history, ethanol consumption, use of illicit drugs, chief complaint, and HIV status. RESULTS: Of 2,473 eligible subjects, 623 (25%) participated. The overall reported prevalence of herbal preparation use among the participants was 21.7%. Women were more likely to use herbal preparations than men (28.5% vs 17.2%, p = 0.013). Prevalence rates in different ethnic populations were: whites, 18.2%; Hispanics, 13.9%; blacks, 26.4%; and Asians, 36.8%. Asians had a significantly higher use rate than the other ethnic groups (p = 0.039). Neither HIV positivity, educational level, employment status, nor age was significantly associated with herbal preparation use. The most commonly reported herbal preparations were goldenseal tea, garlic, and ginger. Several of the herbal preparations reported as used by patients in this study have been associated with severe systemic toxicity in the medical literature. CONCLUSION: Although the survey response rate was low, the prevalence of herbal preparation use among acutely ill or injured patients presenting to this urban ED remains significant. A directed history toward specific herbal preparation use may provide relevant pharmacologic information and uncover cases of herbal-preparation-induced toxicity.

Izzat MB, Yim AP, El-Zufari MH. A taste of Chinese medicine! Ann Thorac Surg 1998;66(3):941-2.
We report a case of profound anticoagulation caused by interaction between warfarin and danshen, a widely used Chinese herbal medicine, in a patient who had undergone mitral valve replacement. Patients taking warfarin should be warned not to take this herb. In addition, physicians should be alert to the possibility of an interaction with herbal medicine when anticoagulation control becomes difficult and no other causes are apparent.

Jappe U, Bonnekoh B, Hausen BM, Gollnick H. Garlic-related dermatoses: case report and review of the literature. Am J Contact Dermat 1999;10(1):37-9.
BACKGROUND: Garlic is widely appreciated as a spice and as a vegetable as well as an over-the-counter phytotherapeutic. From a dermato-allergological standpoint, several garlic-related adverse reactions have to be distinguished. OBJECTIVE: The corresponding literature is reviewed briefly, with regard to our present observation of a cook, who contracted garlic-induced contact dermatitis being analyzed for its complex pathomechanism. METHODS: The patient showed a positive type-IV patch test reaction for diallyl disulfide, a low molecular weight garlic ingredient; and strong, non-irritant reactions after 20 min and 24 hrs in the scratch chamber test with fresh total garlic. RESULTS: Thus, in this case of an occupational dermatosis, protein contact dermatitis had to be considered, as well as allergic type-IV contact dermatitis as a co-existing pathomechanism. CONCLUSIONS: The spectrum of garlic-related adverse reactions comprises irritant contact dermatitis, with the rare variant of zosteriform dermatitis; induction of pemphigus, allergic asthma and rhinitis; contact urticaria; protein contact dermatitis; allergic contact dermatitis, including the hematogenic variant; as well as combinations thereof, as evidenced by our present case observation.

Jappe U, Franke I, Reinhold D, Gollnick HP. Sebotropic drug reaction resulting from kava-kava extract therapy: a new entity? J Am Acad Dermatol 1998;38(1):104-6.

Jensen-Jarolim E, Leitner A, Hirschwehr R, Kraft D, Wuthrich B, Scheiner O, Graf J, Ebner C. Characterization of allergens in Apiaceae spices: anise, fennel, coriander and cumin. Clin Exp Allergy 1997;27(11):1299-306.
BACKGROUND: Symptoms elicited by IgE-mediated food allergy range from mild local to severe systemic reactions. Allergens in spices are particularly dangerous due to their hidden presence in many dishes. OBJECTIVES AND METHODS: According to clinical observations, mugwort and birch pollen allergy, and hypersensitivity to spices are frequently associated, but the crossreacting compounds were not defined so far. We tested sera of 15 patients who experienced adverse reactions to spiced food and characterized their IgE-binding patterns on anise, fennel, coriander and cumin extracts through immunoblot and inhibition experiments. RESULTS: The use of anti-Bet v 1 (MoAb) and anti-profilin (rabbit) antibodies revealed the presence of crossreacting allergens in the tested spice extracts. Inhibition experiments showed that IgE-binding to allergens in Apiaceae spices could be blocked by preincubation of sera with rBet v 1 or rBet v 2 (birch profilin). Moreover, we detected crossreacting allergenic molecules in the molecular weight range of 60 kDa. IgE-binding to spice allergens occurred only with sera of 10/15 (66%) patients with allergy to pollen (birch, mugwort) and/or celeriac. In five out of 15 (33%) patients with a history of adverse reaction to spices, but without pollen and celeriac allergy, no IgE-binding to any spice protein could be demonstrated. It is possible that these clinical reactions could be elicited by other types of hypersensitivity (Type II, III, IV), however, as spices contain highly reactive substances, the symptoms may most likely be classified as food-intolerant. CONCLUSIONS: Bet v 1- and profilin-related allergens may, besides higher molecular weight allergenic molecules, be responsible for Type I allergy to anise, fennel, coriander or cumin, members of the Apiaceae.

Jensen-Jarolim E, Reider N, Fritsch R, Breiteneder H. Fatal outcome of anaphylaxis to camomile-containing enema during labor: a case study. J Allergy Clin Immunol 1998;102(6 Pt 1):1041-2.

Jones TK, Lawson BM. Profound neonatal congestive heart failure caused by maternal consumption of blue cohosh herbal medication. J Pediatr 1998;132(3 Pt 1):550-2.
A newborn infant whose mother ingested an herbal medication, blue cohosh, to promote uterine contractions presented with acute myocardial infarction associated with profound congestive heart failure and shock. The infant remained critically ill for several weeks, although he eventually recovered. Other causes of myocardial infarction were carefully excluded. Blue cohosh, Caulophyllum thalictroides, contains vasoactive glycosides and an alkaloid known to produce toxic effects on the myocardium of laboratory animals. We believe this represents the first described case of deleterious human fetal effects from maternal consumption of blue cohosh.

Joo JS, Ehrenpreis ED, Gonzalez L, Kaye M, Breno S, Wexner SD, Zaitman D, Secrest K. Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited. J Clin Gastroenterol 1998;26(4):283-6.
Cathartic colon is a historic term for the anatomic alteration of the colon secondary to chronic stimulant laxative use. Because some have questioned whether this is a real entity, we investigated changes occurring on barium enema in patients ingesting stimulant laxatives. Our study consisted of two parts. In part 1, a retrospective review of consecutive barium enemas performed on two groups of patients with chronic constipation (group 1, stimulant laxative use [n=29]; group 2, no stimulant laxative use [n=26]) was presented to a radiologist who was blinded to the patient group. A data sheet containing classic descriptions of cathartic colon was completed for each study. Chronic stimulant laxative use was defined as stimulant laxative ingestion more than three times per week for 1 year or longer. To confirm the findings of the retrospective study, 18 consecutive patients who were chronic stimulant laxative users underwent barium enema examination, and data sheets for cathartic colon were completed by another radiologist (part 2). Colonic redundancy (group 1, 34.5%; group 2, 19.2%) and dilatation (group 1, 44.8%; group 2, 23.1%) were frequent radiographic findings in both patient groups and were not significantly different in the two groups. Loss of haustral folds, however, was a common finding in group 1 (27.6%) but was not seen in group 2 (p < 0.005). Loss of haustral markings occurred in 15 (40.5%) of the total stimulant laxative users in the two parts of the study and was seen in the left colon of 6 (40%) patients, in the right colon of 2 (13.3%) patients, in the transverse colon of 5 (33.3%) patients, and in the entire colon of 2 (13.3%) patients. Loss of haustra was seen in patients chronically ingesting bisacodyl, phenolpthalein, senna, and casanthranol. We conclude that long-term stimulant laxative use results in anatomic changes in the colon characterized by loss of haustral folds, a finding that suggests neuronal injury or damage to colonic longitudinal musculature caused by these agents.

Joselice e Silva M, Alves AJ, Do Nascimento SC. Synthesis and cytotoxic activity of N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal. Farmaco 1998;53(3):241-3.
Five new N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal were synthesized. Safrole, a natural product obtained from sassafras oil (Ocotea pretiosa), was oxidized to alcohol using BH3-THF and H2O2, followed by oxidation to aldehyde using pyridinium dichromate (PDC) and condensation with five N-substituted derivatives of thiosemicarbazide. Tests were performed to evaluate the cytotoxic activity with continuous chain KB cells (epidermoide carcinoma of the floor of the mouth). Compounds 5 and 6 showed IC50 values of 1.5 and 4.6 micrograms/ml, respectively.

Kamiyama T, Nouchi T, Kojima S, Murata N, Ikeda T, Sato C. Autoimmune hepatitis triggered by administration of an herbal medicine. Am J Gastroenterol 1997;92(4):703-4.
Although herbal medicines are believed to be safe with few side effects, there are several reports on drug-induced liver injury caused by them. However, there are no reports of autoimmune hepatitis triggered by herbal medicines. We report here the case of a patient with autoimmune hepatitis that became clinically apparent after administration of Dai-saiko-to (Da-Chai-Hu-Tang), an herbal medicine that is used as a standard medicine in Japan.

Kaplowitz N. Hepatotoxicity of herbal remedies: insights into the intricacies of plant-animal warfare and cell death [editorial; comment]. Gastroenterology 1997;113(4):1408-12.

Kobayashi F, Nakamura H, Numata M, Wasada M, Shiraishi K, Itakura M, Matsuzaki S. [A case of drug-induced liver injury caused by Saiko-Keishi-Kankyoto with thrombocytopenia]. Nippon Shokakibyo Gakkai Zasshi 1997;94(10):681-6. (Jpn)

Koh D, Lee BL, Ong HY, Ong CN. Colophony in topical traditional Chinese medicaments. Contact Dermatitis 1997;37(5):243.

Larrey D. Hepatotoxicity of herbal remedies. J Hepatol 1997;26(Suppl 1):47-51.

Lee CT, Wu MS, Lu K, Hsu KT. Renal tubular acidosis, hypokalemic paralysis, rhabdomyolysis, and acute renal failure--a rare presentation of Chinese herbal nephropathy. Ren Fail 1999;21(2):227-30.
We encountered a 66-year-old Chinese man presented with hypokalemic paralysis, rhabdomyolysis and acute renal failure after administration of mixed Chinese herbs. Proximal renal tubular acidosis and selective glucosuria were the main tubular dysfunctions. The renal failure recovered smoothly and rapidly after resuscitation and the tubular function abnormalities regained spontaneously after medicine withdrawal. It should be recognized that renal tubular acidosis with hypokalemic paralysis, rhabdomyolysis and subsequent acute renal failure may develop after taking Chinese mixed herbal medicine.

Leow YH. Contact dermatitis due to topical traditional Chinese medication. Clin Dermatol 1997;15(4):601-5.

Lerner JH. Herbal therapy: there are risks. RN 1997;60(8):53-4.

Levi M, Guchelaar HJ, Woerdenbag HJ, Zhu YP. Acute hepatitis in a patient using a Chinese herbal tea--a case report. Pharm World Sci 1998;20(1):43-4.
A case is presented of reversible acute hepatitis in a patient using a Chinese herbal tea. Upon identification of the tea mixture Aristolochia species, including A. debilis, which contains the highly toxic aristolochic acid, could be identified. We conclude that the acute hepatitis as described in this patient is most likely to be caused by (one of) the active ingredients of the Chinese herbal tea. Furthermore, this case illustrates that so-called natural products can cause unexpected severe adverse reactions.

Liao YL, Chiang YC, Tsai TF, Lee RF, Chan YC, Hsiao CH. Contact leukomelanosis induced by the leaves of Piper betle L. (Piperaceae): a clinical and histopathologic survey. J Am Acad Dermatol 1999;40(4):583-9.
BACKGROUND: In April 1997, an unusual pigmentary disorder was noticed by dermatologists in Taiwan. All patients had a history of using facial dressings with steamed leaves of Piper betle L. (Piperaceae). OBJECTIVE: Our purpose was to clarify the evolution and the origin of this unique leukomelanosis. METHODS: Fifteen patients with an unusual pigmentary disorder, who visited our clinic in September and October 1997, were asked to complete a questionnaire designed to elicit the history related to the disorder. Eight of these 15 patients underwent skin biopsies: 6 on the mottled hyperpigmented area (group A) and 2 on the hypopigmented area (group B). All 8 specimens were prepared with hematoxylin-eosin, Masson-Fontana, and S-100 stains. RESULTS: The results of the questionnaire revealed that these patients had all experienced a temporary erythematous reaction in the first few days of the use of the facial dressing, and 9 of them also complained of an accompanying stinging sensation. A bleaching effect became noticeable approximately 1 week to 1 month later. Eight patients reported that the hyperpigmentation and confetti-like hypopigmentation occurred after overexposure to the sun. In both groups, histopathologic examination revealed some melanophages in the dermis. Masson-Fontana staining of specimens from group A showed local interspersed depigmentation and hyperpigmentation in the basal epidermis and pigmentary incontinence in the dermis. This picture was different from the homogeneous depigmentation within basal epidermis in specimens from group B. In both groups, S-100 staining was negative for melanocytes in the depigmented area. CONCLUSION: The clinical course and histopathologic findings suggest that the evolution of this pigmentary disorder can be divided into 3 stages. The first stage is the immediate bleaching stage, when an irritant reaction is usually conspicuous. The second stage consists of prominent hyperpigmentation visible both grossly and microscopically. The final stage is characterized by confetti-like depigmentation. It may be induced by chemicals in the betel leaves such as phenol, catechol, and benzene derivatives, perhaps through inhibition of melanin synthesis or melanocytotoxicity.

Liaudet L, Buclin T, Jaccard C, Eckert P. Severe ergotism associated with interaction between ritonavir and ergotamine. Br Med J 1999 Mar 20;318:771.
IPA COPYRIGHT: ASHP Severe ergotism attributed to an interaction of 600 mg of ritonavir every 12 h for human immunodeficiency virus (HIV) infection and 0.3 mg ergotamine tartrate twice daily, taken as a combination product with 0.2 mg of belladonna extract and 20 mg of phenobarbital for gastric discomfort, is reported in a 28-yr-old female patient; the patient was also receiving 20 mg/day of fluoxetine for depression. On admission, treatment with intravenous sodium nitroprusside, heparin, and morphine was started. Peridural anesthesia was needed for intractable pain. After 3 days she developed cyanosis and edema in both legs. Intravenous nifedipine, iloprost, and nitrates were also given, but she developed bilateral gangrene of the toes, necessitating transmetatarsal amputation 5 wk later. A proposed mechanism for this interaction, and the possible role of fluoxetine in this severe reaction, are also discussed.

Lichtensteiger CA, Johnston NA, Beasley VR. Rhamnus cathartica (buckthorn) hepatocellular toxicity in mice. Toxicol Pathol 1997;25(5):449-52.
The toxicity of the plant Rhamnus cathartica was assessed in mice after the plant was identified as a potential cause of an idiopathic neurologic disease in horses. Another member of the Rhamnaceae family, Karwinskia humboldtiana, is neurotoxic to mammals and birds and can induce hepatic degeneration and necrosis. To investigate the toxicity of R. cathartica, a 34-day feeding trial in mice was conducted using a complete rodent diet with 0, 5, or 25% added R. cathartica. No clinical signs or gross lesions were seen, and all major tissues were histologically normal except the liver. The livers of mice fed R. cathartica had marked hepatocellular swelling. Results from periodic acid-Schiff reaction staining and from electron microscopy confirmed that the swelling was due to deposits of monoparticulate glycogen (beta particles) in the cytoplasm. Glycogen deposition is an uncommon toxic change in cells. Apparently, compound(s) in R. cathartica directly or indirectly interfered with glycogen metabolism (either glycogenesis or glycogenolysis). Mechanistic and chronicity studies with R. cathartica are needed to investigate the pathophysiology of the glycogen disturbance and to determine if hepatic injury progresses and if other organs will be injured.

Lopez-Rubio A, Rodriguez J, Crespo JF, Vives R, Daroca P, Reano M. Occupational asthma caused by exposure to asparagus: detection of allergens by immunoblotting. Allergy 1998;53(12):1216-20.
BACKGROUND: Vegetables of the Liliaceae family, such as garlic or onion, have been reported to cause occupational asthma. However, there are few data on adverse reactions to asparagus. We evaluated the role of asparagus as a cause of asthma in a patient with respiratory symptoms occurring at work (horticulture) and studied relevant allergens. METHODS: A 28-year-old man complained of rhinoconjunctivitis and asthma when harvesting asparagus at work. Eating cooked asparagus did not provoke symptoms. A positive skin test reaction was observed with raw asparagus, Alternaria alternata, and grass-pollen extracts. The methacholine test demonstrated mild bronchial hyperresponsiveness. The patient had an immediate asthmatic response after challenge with raw asparagus extract. Bronchial provocation tests with boiled asparagus, A. alternata, and control extracts were negative. Two unexposed subjects with seasonal allergic asthma did not react to the raw asparagus extract. RESULTS: The double-blind, placebo-controlled food challenge with raw asparagus was negative. Serum asparagus-specific IgE was 13.9 kU(A)/l. By SDS-PAGE immunoblot, at least six IgE-binding components, ranging from 22 to 73 kDa, were detected only in raw asparagus. CONCLUSIONS: We report a case of occupational asthma caused by asparagus inhalation, confirmed by specific bronchoprovocation. Immunoblot analysis showed that asparagus allergens are very labile and quite sensitive to heat denaturation.

Luty S, Latuszynska J, Halliop J, Tochman A, Obuchowska D, Przylepa E, Korczak E. Toxicity of dermally applied alpha-cypermethrin in rats. Ann Agric Environ Med 1998;5(2):109-16.
The aim of the study was to assess the immunotoxic effect of dermally applied alpha-cypermethrin in rats based on phagocytic and bactericidal activity of neutrophils of peripheral blood, and the general toxic effect based on histological and ultrastructural examination of internal organs. The preparation was dermally applied in doses of 50 mg/kg and 250 mg/kg. It was administered to the tail skin of female Wistar rats, 4 hours daily for 28 days. After the experiment, the animals were anaesthetized and heart blood was taken in order to evaluate the activity of granulocyte system. The following organs were taken for histological examinations: brain, lung, heart, liver, spleen, kidneys, thymus and lymphatic nodes. Lung, liver, kidney and heart were used for ultrastructural studies. The results of the study showed that bactericidal and phagocytic activity of neutrophils was stimulated after administration of 50 mg/kg alpha-cypermethrin. Dermal application of the preparation resulted in slight histological changes in liver, kidney, lung and brain. Pathological changes in heart were observed only on the level of ultrastructure.

Mack RB. "Boldly they rode ... into the mouth of hell". Pennyroyal oil toxicity. N C Med J 1997;58(6):456-7.

Malak J. Chinese herb nephropathy is not a (dex)fenfluramine nephropathy but a serotonin nephropathy [letter; comment]. J Altern Complement Med 1998;4(2):131-2.

Manteiga R, Park DL, Ali SS. Risks associated with consumption of herbal teas. Rev Environ Contam Toxicol 1997;150:1-30.
Plants have been used for medicinal purposes for centuries. Health-oriented individuals are turning to herbal teas as alternatives to caffeinated beverages such as coffee, tea, and cocoa and for low-caloric supplements. The popularity of herbal tea consumption has increased significantly during the past two decades in the U.S. Hundreds of different teas made up of varied mixtures of roots, leaves, seeds, barks, or other parts of shrubs, vines, or trees are sold in health food stores. Although chemists have been characterizing toxic plant constituents for over 100 years, toxicological studies of herbal teas have been limited and, therefore, the safety of many of these products is unknown. Plants synthesize secondary metabolites that are not essential in the production of energy and whose role may be in the defense mechanisms as plant toxins to their interactions with other plants, herbivores, and parasites. Pyrrolizidine alkaloids (PAs) were among the first naturally occurring carcinogens identified in plant products, and their presence in herbal teas is a matter of public health significance. Some herbal tea mixtures and single-ingredient herbal teas have been analyzed for toxic/mutagenic potential by bioassay and chromatographic techniques. Numerous human and animal intoxications have been associated with naturally occurring components, including pyrrolizidine alkaloids, tannins, and safrole. Thus, the prevention of human exposure to carcinogens or mutagens present in herbal tea mixture extracts is crucial. Preparation of infusion drinks prepared from plants appears to concentrate biologically active compounds and is a major source of PA poisoning. The quantity and consumption over a long period of time is of major concern. It is recommended that widespread consumption of herbal infusions should be minimized until data on the levels and varieties of carcinogens, mutagens, and toxicants are made available.

Martin CM. It's only natural: herbal remedies claim their niche. Consult Pharm 1997 Jun;12:631-6.
IPA COPYRIGHT: ASHP An overview of herbal medicines is presented, including research, regulatory issues, and possible benefits and adverse events associated with the use of these popular remedies. Lists of herbs to avoid and resources for natural medicines are presented. Many of the popular herbs on the market that are considered common home remedies are discussed. Herbal dangers with Ginkgo biloba and ginseng are specifically addressed.

Matsuda R, Takahashi D, Chiba E, Kawana I, Tomiyama M, Ebira H, Ikegami T, Kitamura H, Ishii M. [A case of drug induced hepatitis and interstitial pneumonia caused by a herbal drug, Dai-saiko-to]. Nippon Shokakibyo Gakkai Zasshi 1997;94(11):787-91. (Jpn)

Matsushima T. [Drug-induced pneumonitis and related diseases]. Nippon Naika Gakkai Zasshi 1997;86(3):457-62. (Jpn)

Mccain WC, Lee R, Johnson MS, Whaley JE, Ferguson JW, Beall P, Leach G. Acute oral toxicity study of pyridostigmine bromide, permethrin, and DEET in the laboratory rat. J Toxicol Environ Health 1997;50(2):113-24.
This study investigated the lethal interaction of pyridostigmine bromide (PB), permethrin, and DEET when given to adult male rats by gavage and was separated into two phases. Phase I determined the acute oral lethal dose-response relationship of each compound with the vehicle, propylene glycol. Phase II was divided into two portions: a dose-response study using probit units obtained from phase I [lethal dose (LD) 16, 30, 50, 70, and 84], and an interaction study that contained low levels (calculated LD16, additive LD32) of the two compounds while the concentration of the third compound was varied. Rats were fasted overnight, dosed, and observed for 14 d. A significant increase in lethality occurred when PB, permethrin, and DEET were given concurrently when compared to expected additive values. Furthermore, solutions containing PB and permethrin or PB and DEET also caused a significant increase in lethality when compared to expected additive values. This information suggests that lethality in this study was more than an additive effect.

McGovern TW, Barkley TM. Botanical briefs: leafy spurge--Euphorbia esula l. Cutis 1998;62(5):221-2.

McGovern TW, Barkley TM. Botanical briefs: Peruvian lily--Alstroemeria (L.) spp. Cutis 1999;63(3):137-8.

McGovern TW, Barkley TM. Botanical briefs: stinging nettle-Urtical dioica L. Cutis 1998;62(2):63-4.

McGovern TW, Barkley TM. Botanical dermatology. Int J Dermatol 1998;37(5):321-34.
BIOSIS COPYRIGHT: BIOL ABS. RRM LITERATURE REVIEW HUMAN BOTANICAL DERMATOLOGY DERMATOLOGY CONTACT URTICARIA DERMATITIS PHYTOPHOTODERMATITIS ALLERGIC CONTACT DERMATITIS OCCUPATIONAL PLANT DERMATOSIS INTEGUMENTARY SYSTEM DISEASE IMMUNE SYSTEM DISEASE.

McIntyre M. Chinese herbs: risk, side effects, and poisoning: the case for objective reporting and analysis reveals serious misrepresentation [comment] [see comments]. J Altern Complement Med 1998;4(1):15-6.

Mennecier D, Saloum T, Dourthe PM, Bronstein JA, Thiolet C, Farret O. [Acute hepatitis after phytotherapy (letter)]. Presse Med 1999;28(18):966. (Fre)

Miller CA. How safe are herbs? Geriatr Nurs 1998;19(3):163-4.

Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158(20):2200-11.
Herbal medicinals are being used by an increasing number of patients who typically do not advise their clinicians of concomitant use. Known or potential drug-herb interactions exist and should be screened for. If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used with other known hepatoxic drugs, such as anabolic steroids, amiodarone, methotrexate, and ketoconazole. However, Echinacea lacks the 1,2 saturated necrine ring associated with hepatoxicity of pyrrolizidine alkaloids. Nonsteroidal anti-inflammatory drugs may negate the usefulness of feverfew in the treatment of migraine headaches. Feverfew, garlic, Ginkgo, ginger, and ginseng may alter bleeding time and should not be used concomitantly with warfarin sodium. Additionally, ginseng may cause headache, tremulousness, and manic episodes in patients treated with phenelzine sulfate. Ginseng should also not be used with estrogens or corticosteroids because of possible additive effects. Since the mechanism of action of St John wort is uncertain, concomitant use with monoamine oxidase inhibitors and selective serotonin reuptake inhibitors is ill advised. Valerian should not be used concomitantly with barbiturates because excessive sedation may occur. Kyushin, licorice, plantain, uzara root, hawthorn, and ginseng may interfere with either digoxin pharmacodynamically or with digoxin monitoring. Evening primrose oil and borage should not be used with anticonvulsants because they may lower the seizure threshold. Shankapulshpi, an Ayurvedic preparation, may decrease phenytoin levels as well as diminish drug efficacy. Kava when used with alprazolam has resulted in coma. Immunostimulants (eg, Echinacea and zinc) should not be given with immunosuppressants (eg, corticosteroids and cyclosporine). Tannic acids present in some herbs (eg, St John wort and saw palmetto) may inhibit the absorption of iron. Kelp as a source of iodine may interfere with thyroid replacement therapies. Licorice can offset the pharmacological effect of spironolactone. Numerous herbs (eg, karela and ginseng) may affect blood glucose levels and should not be used in patients with diabetes mellitus.

Mochitomi Y, Inoue A, Kawabata H, Ishida S, Kanzaki T. Stevens-Johnson syndrome caused by a health drink (Eberu) containing ophiopogonis tuber. J Dermatol 1998;25(10):662-5.
Stevens-Johnson syndrome is considered to be a severe type of erythema exsudativum multiforme. It is characterized by erythema with bullous and eroded lesions of skin and mucous membranes. We report a case of Steven-Johnson syndrome following consumption of a health drink containing ophiopogonis tuber. A 66-year-old female took an O.T.C. health drink for fever. The next morning, she noted erythema and swelling of her face, neck, and chest. She started to develop bullous and eroded lesions on the skin of her entire body and the mucous membranes of her oral cavity, conjunctiva, and cornea, and she became feverish. She had high degrees of corneal erosion and liver dysfunction. Skin biopsy showed diffuse necrosis of the epidermis. After admission to the hospital, steroid pulse therapy (1000 mg/day of methylprednisolone sodium succinate) was continued for 5 days. The health drink induced a positive drug lymphocyte stimulation test (DLST) and patch test. A challenge test was done with a one hundredth dose, and it was positive. We did patch tests with all components of the drink and found that Mai-Meu-Dong-Tang (ophiopogonis) alone was positive at 72 hours. There is no previous report of Stevens-Johnson syndrome caused by a health drink or Mai-Meu-Dong-Tang. Even though it is a health drink, we should be aware of the possibility of a severe reaction.

Moore DA, Moore NL. Paediatric enema syndrome in a rural African setting. Ann Trop Paediatr 1998;18(2):139-44.
We have observed a distinct clinical syndrome amongst acutely unwell children frequently associated with the administration of a traditional medicine enema. We describe the clinicopathological features of this 'enema syndrome' based on retrospective case note review of 50 consecutive admissions to a South African rural district hospital. Admission was frequently prompted by sudden, marked clinical deterioration following enema administration (68% seen within 24 h). Respiratory distress with tachypnoea, abdominal distension, hypotonia and loss of consciousness occurred frequently. In-hospital mortality was 28% and was higher in those receiving herbal (43%) rather than chemical (21%) enemas. Hyperkalaemia, leucocytosis (> 15,000 mm3) and respiratory distress occurred more frequently in those who died. Diagnosis of an underlying illness was established in 78%. Whilst the majority of enemas are given without incident, children struggling with an underlying illness may be unable to tolerate rectally administered traditional medicines. Toxic chemical substances in frequent use may increase complication rates.

Moss TM. Herbal medicine in the emergency department: a primer for toxicities and treatment. J Emerg Nurs 1998;24(6):509-13.
Herbal therapies are very safe, and side effects are uncommon. Side effects requiring ED treatment are rare and would most likely involve an allergic reaction or toxic effect from improper administration of the herb. However, a working knowledge of possible side effects of herbal therapies can be helpful in those rare instances. Simple treatment options with herbal teas are also suggested as an adjunct to medical therapies in certain instances.

Mukhopadhyay MJ, Saha A, Dutta A, De B, Mukherjee A. Genotoxicity of sennosides on the bone marrow cells of mice. Food Chem Toxicol 1998;36(11):937-40.
Preparations of a number of plants which contain hydroxyanthraquinones as active constituents are used worldwide for their laxative effect. Anthraquinone glycosides of Cassia angustifolia and C. fistula were investigated for their ability to induce a clastogenic effect on the bone marrow cells of Swiss albino mice. The endpoints screened were chromosomal aberrations and frequency of aberrant cells. Oral exposure to doses of these anthraquinones and their equivalent amount in leaf and pod extracts did not induce significant numbers of chromosomal aberrations or aberrant cells. The results indicate that anthraquinone sennoside B and rhein are weakly genotoxic.

Mullins ME, Horowitz BZ. The case of the salad shooters: intravenous injection of wild lettuce extract. Vet Hum Toxicol 1998;40(5):290-1.
Three young adult drug users obtained wild lettuce and valerian root, prepared a crude aqueous extract of the wild lettuce, and injected the extract i.v. One also injected an alcohol extract of the valerian root. All 3 rapidly became ill with fevers, chills, abdominal pain, flank and back pain, neck stiffness, headache, leucocytosis and mild liver function abnormalities, but recovered over the next 3 d. Various literature and internet sources claim that wild lettuce has opiate properties not demonstrated in this case.

Mullins RJ. Echinacea-associated anaphylaxis. Med J Aust 1998;168(4):170-1.
A woman with atopy experienced anaphylaxis after taking, among other dietary supplements, a commercial extract of echinacea. Hypersensitivity was confirmed by skinprick and RAST testing. Regular ingestion of echinacea by up to 5% of surveyed patients with atopy, combined with detection of echinacea-binding IgE in atopic subjects (19% by skin testing; 20% with moderate to strong reactivity by RAST testing), raises the possibility of severe allergic reactions, even with first-time use, due to cross-reactivity with other structurally similar allergens. Patients with atopy should be cautioned about the risk of developing life-threatening reactions to complementary medicines, including echinacea.

Murphy JM. Preoperative considerations with herbal medicines. AORN J 1999;69(1):173-5, 177-8, 180-3.
More patients are using herbal remedies. Even though herbs are natural products, they often act like medications and may interact with or potentiate other medications. During a preoperative evaluation, nurses should ask patients about their use of herbal remedies. Certain herbs are dangerous and should never be taken, and others must be avoided before elective surgery. Today's perioperative health care professionals must become familiar with basic information about herbs to carry out thorough assessments. At times, caregivers may need to educate and counsel consumers about benefits and harmful aspects of herbal preparations.

Musk SR, Clapham P, Johnson IT. Cytotoxicity and genotoxicity of diallyl sulfide and diallyl disulfide towards Chinese hamster ovary cells. Food Chem Toxicol 1997;35(3-4):379-85.
Two compounds found in garlic, diallyl sulfide (DAS) and diallyl disulfide (DDS), were tested for cytotoxic and genotoxic effects in a Chinese hamster ovary cell line. DDS was found to be more cytotoxic than DAS (showing a Dq of 1.6 micrograms/ml and a D0 of 0.6 microgram/ml as opposed to values of 295 and 90 micrograms/ml, respectively). Both compounds were found to induce both chromosome aberrations and sister chromatid exchanges (SCEs) with DDS again being more active on a weight-for-weight basis, exhibiting activity at concentrations below 10 micrograms/ml compared with the levels of 300 micrograms/ml and above required for DAS to show any effect. The addition of rat liver S-9 activation fraction to the assays modified the effects of the two compounds in a non-consistent manner. It reduced the induction of SCEs by both compounds, enhanced the generation of aberrations by DDS (but not by DAS) and radically altered the parameters of both survival curves, reducing the Dq values almost to zero but increasing the D0 values.

Myers JH, Moro-Sutherland D, Shook JE. Anticholinergic poisoning in colicky infants treated with hyoscyamine sulfate. Am J Emerg Med 1997;15(5):532-5.
Hyoscyamine, one of the principal alkaloid components of belladonna, is a potent anticholinergic agent. Because of its anticholinergic properties, hyoscyamine sulfate drops are often prescribed for the treatment of colic in infants. Anticholinergic poisoning in infants is rare. However, five cases are reported of infants with anticholinergic toxicity following the administration of hyoscyamine drops for the treatment of colic. Common presenting symptoms included irritability, tachycardia, and erythematous flushed skin. These cases emphasize the need for a heightened awareness by emergency physicians and pediatricians of possible anticholinergic toxicity caused by the use of hyoscyamine for infant colic.

Myers SP, Wohlmuth H. Echinacea-associated anaphylaxis [letter]. Med J Aust 1998;168(11):583-4.

Nakai T, Kioka K, Sano K, Aoki T, Moriyoshi Y, Kurai O, Nebiki H, Okawa K, Oka H, Harihara S, et al. [A case of drug-induced liver injury by Chinese digestive medicine]. Nippon Shokakibyo Gakkai Zasshi 1998;95(12):1374-7. (Jpn)

Navarro JF, Macia ML, Garcia Perez J. [The false illusion of medicinal herbs (letter; comment) (see comments)]. Med Clin (Barc) 1997;109(4):159. (Spa)

Nguyen B, Weytjens K, Cloutier Y, Ghezzo H, Malo JL. Determinants of the bronchial response to high molecular weight occupational agents in a dry aerosol form. Eur Respir J 1998;12(4):885-8.
In occupational challenge tests with isocyanate vapours, bronchial responsiveness is determined by the total dose rather than the concentration or duration of exposure. Whether the same applies for high molecular weight (HMW) agents in powder form is unknown. The aim of this study was to determine whether the total dose of HMW agents in powder form is responsible for the immediate reaction documented in specific challenge tests. Included in the study were nine subjects (seven males and two females) with a diagnosis of occupational asthma proved by specific challenge tests carried out on a preliminary visit. Two challenge tests (using a closed-circuit exposure chamber) were performed at an interval of 2 weeks; the concentrations administered in a random order on these two visits were half and double the one that had caused a 20% fall in forced expiratory volume in one second (FEV1) on a preliminary visit. The duration of exposure was adjusted until a significant fall in FEV1 (target of 20%) occurred. The two concentrations obtained were significantly different, by 2.07+/-0.36-fold (SD). The observed durations of exposure leading to a 20% fall in FEV1 on the two visits also differed significantly by 0.46+/-0.32-fold. Consequently, the cumulative efficient doses were not significantly different between the two visits: 12+/-5.4 and 9+/-5 mg x mL(-1) x min(-1), respectively. The corresponding cumulative dose ratio was 0.96+/-0.61. The expected duration of exposure (10.8+/-24 min) was not significantly different from the observed duration (5.4+/-9 min). The mean and 95% confidence interval for the difference in concentration between the two visits was 1.83-fold (1.48-2.21). In conclusion, the total dose rather than the concentration or duration of exposure per se determines bronchial responsiveness to high molecular weight agents in powder form.

Nicolie B, Drouet M, Sabbah A. [Chronic rhinitis, or the consequences of gluttony]. Allerg Immunol (Paris) 1997;29(1):22-3. (Fre)

Ning-Sheng L. Renal involvement in Chinese patients with rheumatoid arthritis [letter]. Ann Rheum Dis 1998;57(9):571.

Nortier JL, Deschodt-Lanckman MM, Simon S, Thielemans NO, De Prez EG, Depierreux MF, Tielemans CL, Richard C, Lauwerys RR, Bernard AM, et al. Proximal tubular injury in Chinese herbs nephropathy: monitoring by neutral endopeptidase enzymuria. Kidney Int 1997;51(1):288-93.
Neutral endopeptidase (NEP) is a 94 kDa ectoenzyme of the proximal tubule brush border, physiologically released into the urine with apical membrane fragments. As proximal tubular atrophy was a histological hallmark of Chinese herbs nephropathy (CHN), this study firstly determined renal excretion of NEP in healthy control subjects (N = 31), in patients with CHN (N = 26) and in women having consumed Chinese herbs and whose renal function was normal but running the risk of developing CHN (N = 27). Another patient group consisted of female patients with glomerular diseases (N = 12). At the same time, measurements of urinary microproteins (Clara cell protein, retinol binding protein, beta 2-microglobulin and alpha 1-microglobulin) were performed, as indicators of tubular dysfunction. Cell damage was estimated by the excretion of N-acetyl-beta-D-glucosaminidase (NAG). In the control group, the physiological NEP enzymuria was 43.1 micrograms/24 hr (geometric mean). In CHN patients, levels of urinary NEP were significantly decreased in those with moderate renal failure (26.7 micrograms/24 hr; N = 21; P < 0.05) and almost abolished in end-stage renal failure patients (4.35 micrograms/24 hr; N = 5; P < 0.05). In patients at risk as well as in patients with glomerular diseases, urinary NEP levels were not statistically different from those observed in control subjects (40.68 micrograms/24 hr and 48.5 micrograms/24 hr, respectively). Several degrees of tubular dysfunction and injury were noted in patients groups, as attested by increased urinary microproteins and NAG excretions. Considering the data from control and CHN patients, NEP enzymuria positively correlated with individual creatinine clearance values (r = 0.76; P = 0.0001) and negatively correlated with urinary microproteins levels (r = -0.55; P = 0.00001). Finally, NEP was regularly quantitated in the urine of 6 CHN patients for a period ranging from six months to two years and in 19 patients at risk during two years, respectively. In the first group, renal function progressively deteriorated in 3 patients, leading them to renal replacement therapy after 38 to 115 weeks. Stable parameters were observed in the remaining 3 patients. A direct correlation between creatinine clearance and NEP excretion was found longitudinally in each case. In the second group, no significant change of urinary NEP levels was observed (45.9 micrograms/24 hr), in parallel with stable renal function. Taken together, these results indicate that, in CHN patients, NEP enzymuria provides a rapid and noninvasive determination of the degree of structural impairment affecting the proximal tubular population and further reflecting the severity of the renal disease. The interest of this urinary marker in monitoring the progression of other tubulointerstitial diseases remains to be assessed.

O'Breasail AM, Argouarch S. Hypomania and St John's wort [letter]. Can J Psychiatry 1998;43(7):746-7.

Oda H, Ono M, Ohashi H. [Probable case of Chinese herbs nephropathy]. Nippon Naika Gakkai Zasshi 1998;87(11):2309-10. (Jpn)

Oertmann C, Bergmann KC. [The increase of pollen-associated oral allergy syndrome: The marker of a change in pollen allergy]. Allergologie 1997;20(12):611-9. (Ger)
BIOSIS COPYRIGHT: BIOL ABS. The histories of pollen-associated food intolerance were obtained from questionnaires of patients with pollinosis at a hospital for allergies and diseases of the airways. The comparisons were made between 300 consecutive individual cases examined between 1979-1983 and again 300 cases between 1995-1996. The prevalence of oral allergy syndrome (OAS), particularly that produced by apples, nuts, stone and kernel fruits was 17.3% 15 years ago as opposed to 58.3% for todays figures. Almost no difference was to be observed in non-pollen-associated food intolerances. The pollen skin test showed the same frequency of tree pollen sensitization in both groups (267:264). Whilst particularly trivalent sensitizations to trees, herbs and grasses were found (238) 15 years ago, this was evident in only 133 cases for 1995-1996. However, the monovalent sensitization to trees alone increased from 2 to 55 (0,6% to 18,5%) and bivalent sensitization to trees and grasses showed an increase from 5,7% to 22.1%. Additionally, a high percentage of those patients with mono and bivalent sensitizations to trees also suffered from OAS, caused by the high identity of Bet v1 and the major allergens in apples and nuts. Thus the observed increase of OAS conforms with a higher potency of tree pollen allergy manifesting itself in mono and bivalent form - even in patients less disposed to allergies. This assumption is backed by the fact that a higher percentage of older patients had monovalent pollen allergy, grown "forced" over years whereas the younger patients of extreme allergic disposition more frequently showed a trivalent sensitization. In 1995-1996 the PRIST value was determined in 167 patients with pollinosis. This demonstrates that the level of total IgE is not significant for OAS. A heightened exposure to sensitizing tree pollen is probably of more significance today. Thus OAS is a marker syndrome indicating a change in pollinosis today more often due to tree pollen allergy whereas sensitization to grassesand herbs almost remained the same within the time period of comparison.

Oka K, Saito F, Yasuhara T, Sugimoto A. The allergens of Dendropanax trifidus Makino and Fatsia japonica Decne. et Planch. and evaluation of cross-reactions with other plants of the Araliaceae family. Contact Dermatitis 1999;40(4):209-13.
cis-9,17-Octadecadiene-12,14-diyne-1,16-diol (I), an analog of falcarinol has been identified in our previous report as an active component of Dendropanax trifidus and a strong sensitizer. In this report, 16-hydroxy-cis-9,17-octadecadiene-12,14-diynoic acid (II) and cis-9,trans-16-octadecadiene-12,14-diynoic acid (III) were elucidated as 2 other active components of the plant. Compound I, however, presented with the highest concentration and showed a stronger reaction on patch testing. The leaves of Fatsia japonica Decne. et Planch. were also found to contain compound I, but the amount was found to be 7x more in Dendropanax trifidus than in Fatsia japonica. 5 subjects with hypersensitivity to Dendropanax trifidus and compound I showed positive reactions when patch tested with the leaves of Hedera helix L. and Schefflera arboricola. 1 of these also showed a positive reaction to the extract of Panax ginseng root powder diluted 1% in ethanol. There was cross-reaction among these plants, which all belong to the Araliaceae family.

Ondrizek RR, Chan PJ, Patton WC, King A. An alternative medicine study of herbal effects on the penetration of zona-free hamster oocytes and the integrity of sperm deoxyribonucleic acid. Fertil Steril 1999;71(3):517-22.
OBJECTIVE: To analyze the effects of certain herbs on sperm DNA and on the fertilization process. DESIGN: Prospective comparative study. SETTING: Clinical and academic research environment. PATIENT(S): Donor sperm specimens. INTERVENTION(S): Zona-free hamster oocytes were incubated for 1 hour in saw palmetto (Serenoa repens), echinacea purpura, ginkgo biloba, St. John's wort (Hypericum perforatum), or control medium before sperm-oocyte interaction. The DNA of herb-treated sperm was analyzed with denaturing gradient gel electrophoresis. MAIN OUTCOME MEASURE(S): Oocyte penetration and integrity of the sperm BRCAI exon 11 gene. RESULT(S): Pretreatment of oocytes with 0.6 mg/mL of St. John's wort resulted in zero penetration. A lower concentration (0.06 mg/mL) had no effect. High concentrations of echinacea and ginkgo also resulted in reduced oocyte penetration. Exposure of sperm to echinacea purpura and St. John's wort resulted in DNA denaturation. In contrast, saw palmetto and ginkgo had no effect. Sperm exposed to 0.6 mg/mL of St. John's wort showed mutation of the BRCA1 exon 11 gene. CONCLUSION(S): High concentrations of St. John's wort, echinacea, and ginkgo had adverse effects on oocytes. Saw palmetto had no effect. The data suggested that St. John's wort, ginkgo, and echinacea at high concentrations damage reproductive cells. St. John's wort was mutagenic to sperm cells.

Ono T, Eri M, Honda G, Kuwahara T. Valvular heart disease and Chinese-herb nephropathy [letter; comment]. Lancet 1998;351(9107):991-2.

Paulsen E. Occupational dermatitis in Danish gardeners and greenhouse workers (II). Etiological factors. Contact Dermatitis 1998;38(1):14-9.
The aim of the study was to assess the distribution of different types of occupational eczema among employees in floristry and detect the allergens most commonly involved. Based on a postal questionnaire, 253 gardeners and greenhouse workers with occupational skin symptoms and 52 randomly-selected without symptoms were examined and patch tested. Routine tests comprised the standard series, the Compositae mix, feverfew and 3 fungicides, with additional testing based on case records. 184 persons from the symptom group and 1 from the random group had occupational eczema. Irritant occupational contact eczema was suspected in 150 persons (59%). Nevertheless, 48% of the 250 persons patch tested had at least 1 positive reaction, most frequently to nickel, followed by Compositae which were positive in 25 cases (10%), of whom 24 were possibly occupationally sensitized. 13 persons from symptom group had positive reactions to fungicides. Occupational allergic eczema was suspected in 43 persons (17%), most often caused by plants belonging to the Compositae, Geraniaceae and Liliaceae families. New plant sensitizers were Exacum affine and Begonia lorraine. Exposure to specific plant species seemed to be the most important eliciting factors in both allergic and irritant occupational dermatitis in floristry, and preventive measures should include reduction of contact with plants.

Paulsen E, Sogaard J, Andersen KE. Occupational dermatitis in Danish gardeners and greenhouse workers (III). Compositae-related symptoms. Contact Dermatitis 1998;38(3):140-6.
The clinical part of the study aimed at describing epidemiological and diagnostic aspects of occupational Compositae dermatitis. Patch testing with the sesquiterpene lactone (SL) and Compositae mixes, feverfew extract and supplementary allergens in 250 selected gardeners showed Compositae allergy in 25, 17 females and 8 males. 24 were possibly occupationally sensitized. The mean age was lower and the preponderance of women higher compared to classical Compositae dermatitis, and the distribution and course of the dermatitis most often did not differ from other occupational plant dermatoses. The Compositae mix detected 2x as many as the SL mix, and the overall detection rate with both was 76%, making aimed patch testing necessary. Chrysanthemum (Dendranthema), marguerite daisy (Argyranthemum frutescens) and lettuce (Lactuca sativa) were frequent sensitizers. Occupational type I allergy to Compositae comprised sensitization to Gerbera, chrysanthemum, lettuce, Senecio cruentus and Aster. Among 1657 respondents in the questionnaire part of the study, 824 had worked with Compositae, and 160 (19%) reported occupational Compositae-related symptoms of skin and mucous membranes. Possible risk factors for the development of these were assessed in a stepwise logistic regression model and a history of childhood eczema, hay fever and duration of exposure were significantly associated with Compositae-related irritant and allergic symptoms in both sexes.

Pfutzner W, Thomas P, Rueff F, Przybilla B. Anaphylactic reaction elicited by condurango bark in a patient allergic to natural rubber latex. J Allergol Clin Immunol 1887;101(2 Pt 1):281-2.
BIOSIS COPYRIGHT: BIOL ABS. RRM CASE STUDY MARSDENIA-CONDURANGO HUMAN ADULT MALE NURSE PATIENT NATURAL RUBBER LATEX NATURAL RUBBER LATEX ALLERGY CUNDURANGO BARK ANAPHYLACTIC REACTION HERBAL TEA ALLERGY ALLERGEN IMMUNE SYSTEM DISEASE TEA.

Phan TG, Estell J, Duggin G, Beer I, Smith D, Ferson MJ. Lead poisoning from drinking Kombucha tea brewed in a ceramic pot. Med J Aust 1998;169(11-12):644-6.
Kombucha tea is an alternative therapy that is gaining popularity as a remedy for a diverse range of ailments. We report two cases of symptomatic lead poisoning requiring chelation therapy in a married couple who had been drinking Kombucha tea for six months, brewing the tea in a ceramic pot. We postulate that acids in the tea eluted lead from the glaze pigment used in the ceramic pot, in a manner analogous to elution of lead from crystal decanters by wine and spirits.

Picciotto A, Campo N, Brizzolara R, Giusto R, Guido G, Sinelli N, Lapertosa G, Celle G. Chronic hepatitis induced by Jin Bu Huan. J Hepatol 1998;28(1):165-7.
BACKGROUND/AIMS: Jin Bu Huan and other Chinese herbal products are widely taken remedies. They have been developed as a natural alternative to traditional drugs in the treatment of various ailments. Their ability to induce several side effects such as acute hepatitis has already been described. We report a case of chronic hepatic damage following administration of Jin Bu Huan Anodyne tablets. METHODS: The patient, a 49-year-old man, developed biochemical signs of liver damage 2 months after beginning Jin Bu Huan intake (3 tablets/daily) including biopsy-proven chronic hepatitis with moderate fibrosis. Virological, autoimmune, metabolic or other hepatotoxic causes were excluded. Liver function impairment was resolved by discontinuing Jin Bu Huan intake. CONCLUSIONS: This case reinforces the already known hepatotoxicity of this product and should make us think more about the uncontrolled use of alternative products.

Powell T, Hsu FF, Turk J, Hruska K. Ma-huang strikes again: ephedrine nephrolithiasis. Am J Kidney Dis 1998;32(1):153-9.
Ephedrine and its metabolites are naturally occurring alkaloids that can be derived from evergreens worldwide and have been used as medicinals for hundreds of years. Because they have "real" pharmacological alpha and beta catecholamine effects and are "natural" products, the alternative medicine industry has popularized them for multiple uses, including asthma, weight loss, energy and sexual enhancement, and euphoria. Several recent reviews have documented the dangerous nature of using these "drugs" unsupervised, including multiple deaths, and the FDA is currently reviewing ephedrine's use in the alternative medicine industry. We report a new toxicity, ephedrine nephrolithiasis, in a patient using an energy supplement, Ma-Huang extract, which contains ephedrine. Although previously not reported, the Louis C. Herring and Company kidney stone database show that this is an endemic complication of ephedrine with hundreds of previous episodes. Using gas chromatography (GC) mass spectrometry, we were able to positively identify the chemical structure of our patient's stone, as well as other similar stones from Louis Herring, as containing ephedrine, norephedrine, and pseudoephedrine.

Reginster F, Jadoul M, Van Ypersele De Strihou C. Chinese herbs nephropathy presentation, natural history and fate after transplantation. Nephrol Dial Transplant 1997;12(1):81-6.
BACKGROUND: Chinese herbs nephropathy is a new type of subacute interstitial nephropathy reported in women who had followed a slimming regimen including Chinese herbs. METHODS: We report the clinical presentation and follow-up of 15 cases and compare them with a control group of 15 women with interstitial nephropathies of other origins, matched for age, sex, and initial serum creatinine (mean 3 mg/dl). RESULTS: At presentation the Chinese herbs nephropathy group differed from the control group by a lower proteinuria (P = 0.009), a more severe anaemia (P = 0.002), and a higher prevalence of aortic insufficiency (42% vs 0%, P < 0.05). It was further characterized by mild hypertension in 80%, glycosuria and leukocyturia in 40% and asymmetric kidneys in 54% of the cases. During follow-up, deterioration of renal function was faster in the Chinese herbs nephropathy than in the control group (P < 0.05). It was influenced by the duration of Chinese herbs treatment (P = 0.037) and the delay between the end of Chinese herbs ingestion and diagnosis of the disease (P = 0.013). In three cases, renal failure developed 3 years after Chinese herbs ingestion. Complications included severe aortic regurgitation requiring surgery (n = 1), urothelial carcinoma (n = 2), bilateral ureterohydronephrosis due to periureteral fibrosis (n = 1). Five patients with Chinese herbs nephropathy were successfully transplanted, without evidence of recurrence of the disease. CONCLUSIONS: Chinese herbs nephropathy is characterized by a lower proteinuria, more severe anaemia, and a faster progression to renal failure than other interstitial nephropathies. The duration of Chinese herbs treatment and interval between withdrawal of Chinese herbs and diagnosis are correlated with the rate of progression. Severe, unusual extrarenal complications may affect Chinese herbs nephropathy patients.

Rodriguez-Serna M, Sanchez-Motilla JM, Ramon R, Aliaga A. Allergic and systemic contact dermatitis from Matricaria chamomilla tea. Contact Dermatitis 1998;39(4):192-3.

Rudzki E, Rebandel P. Positive patch test with Kamillosan in a patient with hypersensitivity to camomile. Contact Dermatitis 1998;38(3):164.

Ryu JC, Kim KR, Kim HJ, Youn JY, Myung SW, Kim GH, Lee MJ, Chang IM. Genotoxicity study of bojungchisup-tang, an oriental herbal decoction-in vitro chromosome aberration assay in Chinese hamster lung cells and in vivo supravital-staining micronucleus assay with mouse peripheral reticulocytes. Arch Pharm Res 1998;21(4):391-7.
The toxicity evaluation of oriental herbal drugs is of great concern at present. Bojungchisuptang (BCST, in Korean), a decocted medicine of oriental herbal mixture, is now well used in clinic at oriental hospitals for the treatment of edema of several diseases in practice. However, the toxicity of the oriental herbal decocted medicines such as genetic toxicity is not well defined until now. In this respect, to clarify the genetic toxicity of BCST, in vitro chromosome aberration assay with Chinese hamster lung (CHL) fibroblasts and in vivo supravital micronucleus assay with mouse peripheral reticulocytes were performed in this study. In the chromosome aberration assay, we used 5,000 micrograms/ml BCST as maximum concentration because no remarkable cytotoxicity in CHL cells was observed both in the presence and absence of S-9 metabolic activation system. No statistical significant differences of chromosome aberrations were observed in CHL cells treated with 5,000, 2,500 and 1,250 micrograms/ml BCST for 6 hour both in the presence and absence of S-9 metabolic activation. However, very weak positive result (6.5-8.0% aberration) of BCST was obtained in the absence of S-9 metabolic activation system at 5,000 micrograms/ml BCST when treated for 24 hour, i.e. 1.5 normal cell cycle time. And also, in vivo clastogenicity of BCST was studied by acridine orange-supravital staining micronucleus assay using mouse peripheral reticulocytes. We used 2,000 mg/kg as the highest oral dose in this micronucleus assay because no acute oral toxicity of BCST was observed in mice. The optimum induction time of micronucleated reticulocytes (MNRETs) was determined as 36 hours after oral administration of 2,000 mg/kg BCST. No significant differences of MNRETs between control and BCST treatment groups were observed in vivo micronucleus assay. From these results, BCST revealed very weak positive result in chromosome aberration assay in vitro with CHL cells and no clastogenicity in micronucleus assay in vivo.

Sadjadi J. Cutaneous anthrax associated with the Kombucha "mushroom" in Iran [letter]. JAMA 1998;280(18):1567-8.

Santa Maria A, Lopez A, Diaz MM, Munoz-Mingarro D, Pozuelo JM. Evaluation of the toxicity of guarana with in vitro bioassays. Ecotoxicol Environ Saf 1998;39(3):164-7.
A natural stimulant, Paullinia cupana, commonly called guarana, was tested for its ability to induce in vitro toxicity in Chinese hamster ovary (CHO) cells and bacterial cells (Photobacterium phosphoreum). The cytotoxic effects of aqueous guarana extracts were evaluated by three endpoint systems: neutral red (NR) uptake assay, total protein content [kenacid blue (KB)] assay, and tetrazolium (MTT) assay. The Microtox test was also used. Results indicated that the lowest concentration of guarana tested was not toxic and that the IC50 values calculated with the NR, KB, and MTT assays were lower than the highest concentration tested (40 mg/ml). There was no significant difference in cytotoxicity between the three test systems. The EC50 values obtained with the Microtox assay were consistent with these data. The present in vitro analysis suggests that the concentration of guarana is of critical importance in its cytotoxic activity and high doses could be harmful to human health.

Schilcher H, Leuschner F. [Studies of potential nephrotoxic effects of essential juniper oil]. Arzneimittelforschung 1997;47(7):855-8. (Ger)
BIOSIS COPYRIGHT: BIOL ABS. The nephrotoxicity of juniper oil (CAS 73049-62-4), a phytomedicine with diuretic resp. aquaretic activity, was evaluated in male Sprague-Dawley rats after oral administration. Two chemically slightly different oil batches were tested for 28 days with 100, 333 or 1000 mg (series 1, batch 1) resp. 100, 300 or 900 mg (series 2, batch 2) juniper oil/kg. Additionally terpinene-4-ol, a compound with postulated aquaretic activity, which can be found in essential juniper oil up to an amount of 10 mg% was tested in a dosage of 400 mg/kg. Neither of the tested substances induced changes in function or morphology of the kidneys at the tested doses, and they were revealed to be nontoxic.

Schwartz HJ, Jones RT, Rojas AR, Squillace DL, Yunginger JW. Occupational allergic rhinoconjunctivitis and asthma due to fennel seed. Ann Allergy Asthma Immunol 1997;78(1):37-40.
BACKGROUND: A patient with complaints of rhinitis and asthma occurring at work presented for consultation. OBJECTIVES: To evaluate the role of the foods and spices with which he worked, in the causation of his complaints, and to evaluate his immune reactivity to these materials. METHODS: Allergy skin testing and in vitro RAST assays were carried out. After demonstrating specific reactivity to fennel, SDS-PAGE electrophoreses was carried out. RESULTS: Positive skin tests to grass, ragweed, and freshly prepared fennel seed were found. Serum IgE antibodies to fennel were quite high. Immunoblotting studies showed reactions to two components in fennel extract as well as to components in mugwort, paprika, short ragweed and black pepper. CONCLUSION: This case of occupational rhinitis and asthma in an atopic individual involves sensitivity to unique allergens in fennel, with molecular weights of 67 to 75 KD.

See DM, Broumand N, Sahl L, Tilles JG. In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharmacology 1997;35(3):229-35.
Extracts of Echinacea purpurea and Panax ginseng were evaluated for their capacity to stimulate cellular immune function by peripheral blood mononuclear cells (PBMC) from normal individuals and patients with either the chronic fatigue syndrome or the acquired immunodeficiency syndrome. PBMC isolated on a Ficoll-hypaque density gradient were tested in the presence or absence of varying concentrations of each extract for natural killer (NK) cell activity versus K562 cells and antibody-dependent cellular cytotoxicity (ADCC) against human herpesvirus 6 infected H9 cells. Both echinacea and ginseng, at concentrations > or = 0.1 or 10 micrograms/kg, respectively, significantly enhanced NK-function of all groups. Similarly, the addition of either herb significantly increased ADCC of PBMC from all subject groups. Thus, extracts of Echinacea purpurea and Panax ginseng enhance cellular immune function of PBMC both from normal individuals and patients with depressed cellular immunity.

Seong YH, Kim HS. Inhibitory effects of ginseng total saponins on hypoxia-induced dysfunction and injuries of cultured astrocytes. Arch Pharmacal Res 1997;20(2):103-9.

Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements. A 5-year toxicological study (1991-1995). Drug Saf 1997;17(5):342-56.
Since 1991, the Medical Toxicology Unit (MTU) at Guys' Hospital, London, has been assessing the toxicological problems associated with the use of traditional and herbal remedies and dietary supplements. This assessment was carried out by evaluating reports to the National Poisons Information Service (London) [NPIS(L)] which provides emergency information to medical professionals. Relevant telephone enquiries to NPIS(L) were identified. Further case details were obtained by follow-up questionnaire, clinical consultation, toxicological analysis of samples from patients and/or products and botanical identification of plant material. Of 1297 symptomatic enquiries evaluated there was a possible/confirmed association in 785 cases. Case series have been identified which substantiate previous reports, including liver problems following the use of Chinese herbal medicine for skin disorders, allergic reactions to royal jelly and propolis and heavy metal poisoning caused by remedies from the Indian subcontinent. Although the overall risk to public health appears to be low, certain groups of traditional remedies have been associated with a number of potentially serious adverse effects. Considering the extent of use of herbal remedies and food supplements a comprehensive surveillance system for monitoring the adverse health effects of these products is essential. Surveillance of a large population is needed for the complex task of identifying the uncommon and unpredictable adverse effects which are potentially serious. In the UK, the Medicines Control Agency responded to the MTU report by recognising the need for vigilance and by incorporating adverse reactions reporting on unlicensed herbal remedies into their drug reaction monitoring function. As a further step to safeguard the patients/consumers an effective single regulatory system is required which would ensure the safety and quality of all herbal remedies and food supplements available in the UK.

Shaw D, Murray V, Volans G. Adverse effects of herbal remedies and OTC medicines [letter]. Br J Clin Pharmacol 1999;47(2):227-8; Discusion 229-30.

Sheehan DM. Herbal medicines, phytoestrogens and toxicity: risk:benefit considerations. Proc Soc Exp Biol Med 1998;217(3):379-85.
There are several suggested health benefits of phytoestrogens, particularly those found in soy products. Herbal medicines are also widely thought to confer health benefits. Additionally, drugs are prescribed to improve human health, but unlike phytoestrogens and herbal medicines, toxicities are defined in experimental animals and monitored in humans before and after marketing. Knowledge of toxicity is crucial to decrease the risk:benefit ratio; this knowledge defines appropriate conditions for use and strategies for development of safer products. However, our awareness of the toxicity of herbal medicines and phytoestrogen-containing foods is dramatically limited compared to drugs. Some aspects of the toxicity of herbal medicines are briefly reviewed; it is concluded that virtually all of our knowledge is derived from human exposures leading to acute toxicities. Importantly, detection of toxicity is sporadic, and little information is available from prior animal experimentation. Additionally, well-organized monitoring of human populations (as occurs for drugs) is virtually nonexistent. Important toxicities with long latencies are particularly difficult to associate with a causative agent during or even after large scale exposures, as exemplified by tobacco smoking and lung cancer; estrogen replacement therapy and endometrial cancer; diethylstilbestrol and reproductive tract cancers; and fetal alcohol exposure and birth defects. These considerations suggest that much closer study in experimental animals and human populations exposed to phytoestrogen-containing products, and particularly soy-based foods, is necessary. Among human exposures, infant soy formula exposure appears to provide the highest of all phytoestrogen doses, and this occurs during development, often the most sensitive life-stage for induction of toxicity. Large, carefully controlled studies in this exposed infant population are a high priority.

Sheikh NM, Philen RM, Love LA. Chaparral-associated hepatotoxicity. Arch Intern Med 1997;157(8):913-9.
BACKGROUND: Personal health care practices that may include the use of dietary supplements are common in the United States. Products marketed as dietary supplements are diverse and may include botanicals, vitamins, and/or minerals. Chaparral (Larrea tridentata) is a botanical dietary supplement made from a desert shrub and used for its antioxidant properties. Several reports of chaparral-associated hepatitis have been published since 1990, but a complete picture of the clinical presentation is still unclear. MATERIALS AND METHODS: We reviewed the 18 case reports of adverse events associated with the ingestion of chaparral reported to the Food and Drug Administration between 1992 and 1994. These reports were from health care professionals, state health departments, and individual consumers. RESULTS: Of 18 reports of illnesses associated with the ingestion of chaparral, there was evidence of hepatotoxicity in 13 cases. Clinical presentation, characterized as jaundice with a marked increase in serum liver chemistry values, occurred 3 to 52 weeks after the ingestion of chaparral, and it resolved 1 to 17 weeks after most individuals stopped their intake of chaparral. The predominant pattern of liver injury was characterized as toxic or drug-induced cholestatic hepatitis; in 4 individuals, there was progression to cirrhosis; and in 2 individuals, there was acute fulminant liver failure that required liver transplants. CONCLUSIONS: These data indicate that the use of chaparral may be associated with acute to chronic irreversible liver damage with fulminant hepatic failure, and they underscore the potential for certain dietary supplement ingredients to cause toxic effects on the liver. Health professionals should be encouraged to inquire routinely about the use of dietary supplements and other products, to be alert to potential adverse effects that may be associated with these products, and, finally, to report any serious adverse events associated with these products through the MEDWatch Program of the Food and Drug Administration.

Shulman LM, Minagar A, Weiner WJ. Perdiem causing esophageal obstruction in Parkinson's disease. Neurology 1999;52(3):670-1.

Slifman NR, Obermeyer WR, Aloi BK, Musser SM, Correll WA Jr, Cichowicz SM, Betz JM, Love LA. Contamination of botanical dietary supplements by Digitalis lanata [see comments]. N Engl J Med 1998;339(12):806-11.

Spillane PK, Fisher DA, Currie BJ. Neurological manifestations of kava intoxication [letter] [see comments]. Med J Aust 1997;167(3):172-3.

Srinivasan R, Smolinske S, Greenbaum D. Probable gastrointestinal toxicity of Kombucha tea: is this beverage healthy or harmful? J Gen Intern Med 1997;12(10):643-4.
Kombucha tea is a health beverage made by incubating the Kombucha "mushroom" in tea and sugar. Although therapeutic benefits have been attributed to the drink, neither its beneficial effects nor adverse side effects have been reported widely in the scientific literature. Side effects probably related to consumption of Kombucha tea are reported in four patients. Two presented with symptoms of allergic reaction, the third with jaundice, and the fourth with nausea, vomiting, and head and neck pain. In all four, use of Kombucha tea in proximity to onset of symptoms and symptom resolution on cessation of tea drinking suggest a probable etiologic association.

Steinmann A, Schatzle M, Agathos M, Breit R. Allergic contact dermatitis from black cumin (Nigella sativa) oil after topical use. Contact Dermatitis 1997;36(5):268-9.

Stewart MJ, Steenkamp V, Zuckerman M. The toxicology of African herbal remedies. Ther Drug Monit 1998;20(5):510-6.
Toxicity related to traditional medicines is becoming more widely recognized as these remedies become popular in developed countries. Accidental herbal toxicity occurs not only as a result of a lack of pharmaceutic quality control in harvesting and preparation but also because herbal remedies are believed to be harmless. Although there is a huge amount of data available documenting the pharmacologically active ingredients of many plants, it is seldom helpful to the toxicologist in an acute situation. Current analytic methods such as high-performance liquid chromatography, gas chromatography--mass spectrometry, and immunoassays can provide identification of the toxin in those few cases in which the history or symptoms give a clear lead, but broad screening methods remain to be developed. In most cases of plant poisoning, treatment continues to be only of symptoms, with few specific antidotes available. It is important that toxicologists in the West be alert to the possibility of encountering poisoning in patients due to traditional African remedies.

Takei A, Nagashima G, Suzuki R, Hokaku H, Takahashi M, Miyo T, Asai J, Sanada Y, Fujimoto T. Meningoencephalocele associated with Tripterygium wilfordii treatment. Pediatr Neurosurg 1997;27(1):45-8.
We treated a male infant with occipital meningoencephalocele associated with the taking of Tripterygium wilfordii. The infant was delivered normally at 38 weeks of gestation with a huge cystic mass protruding from the occiput. He was diagnosed with occipital meningoencephalocele and cerebellar agenesis. His mother had taken T. wilfordii for rheumatoid arthritis early in her pregnancy. T. wilfordii is a herbal medicine used for rheumatoid arthritis and male contraception. Since its toxicity is high and its use during pregnancy is restricted, it is the most likely cause of this infant's anomalies.

Tan PH, Chou AK, Perng JS. Accidental shock during epidural anesthesia in a patient with NSAID-induced hyporeninemic hypoaldosteronism. J Clin Anesth 1997;9(5):424-7.
An obese man suffered cardiac arrest twenty minutes after receiving epidural anesthesia for incision and debridement of wound over the right leg. The patient's condition stabilized after emergent cardiopulmonary resuscitation. It was found that the patient had been self-administering an herbal drug continuously for a year and a half, and that this drug contained ethoxybenzamide, which is a nonsteroidal anti-inflammatory drug (NSAID). Low plasma renin and aldosterone levels were noted from the blood sample taken at the time of the cardiac arrest. The cardiac arrest was believed to be related to NSAID-induced hyporeninemic hypoaldosteronism, superimposed with epidural anesthesia-induced sympathectomy.

Tanaka I. [Case of chronic renal tubular interstitial nephritis with syndrome of disappearing bile ducts (letter)]. Nippon Naika Gakkai Zasshi 1998;87(8):1601. (Jpn)

Thompson CA. Adverse reactions to alternative medicine. Am J Health Syst Pharm 1997 Aug 1;54:1707.
IPA COPYRIGHT: ASHP The lack of data regarding adverse reactions to vitamins, minerals, and herbs marketed as alternative medical products due to a 1994 federal law that declassified these products as food is discussed, including the role of manufacturers in quality control of these products, current U.S. Food and Drug Administration (FDA) activities regarding new regulations and Good Manufacturing Practices for the dietary supplements industry, and the role of pharmacists in monitoring patients who use these supplements and reporting any adverse reactions to them.

Tomas ME, Garfia C, Marcos MS, Casis B, Perez-Carreras M, Manzano ML, Yela C. [Intense cholestasis associated with medicinal herbs (letter]. Rev Esp Enferm Dig 1998;90(7):529-30. (Spa)

Tsiodras S, Shin RK, Christian M, Shaw LM, Sass DA. Anticholinergic toxicity associated with lupine seeds as a home remedy for diabetes mellitus. Ann Emerg Med 1999;33(6):715-7.
We describe a case of sparteine intoxication associated with using a preparation from lupine seeds. A female patient of Portuguese origin presented to the emergency department with classic anticholinergic signs after ingestion of a lupine seed extract. She took the preparation with the belief it represented a cure for her recently diagnosed diabetes. Analysis of the patient's lupine bean extract identified the preponderant compound as oxo-sparteine by gas chromatography/mass spectrometry. Intoxication by lupine seeds rarely occurs in human beings. To our knowledge, no medical or toxicologic evidence supports a belief that lupine extract could lower serum glucose levels. This case highlights the need for emergency care providers to be aware of the health hazards that can be associated with the use of such home remedies.

Van Ypersele De Strihou C. Chinese herbs nephropathy or the evils of nature. Am J Kidney Dis 1998;32(3):l-Lii.

Van Ypersele De Strihou C. Chinese herbs nephropathy or the evils of nature [letter]. Am J Kidney Dis 1999;33(2):412.

Van Ypersele De Strihou C. [Gentle medicine, harmless medicine? (editorial)]. Nephrologie 1998;19(1):5-6. (Fre)

Van Ypersele De Strihou C. Valvular heart disease and Chinese-herb nephropathy [letter; comment]. Lancet 1998;351(9107):991-2.

Vanherweghem JL. Association of valvular heart disease with Chinese-herb nephropathy [letter; comment] [see comments]. Lancet 1997;350(9094):1858.

Vanherweghem JL. Nephrotoxicitiy of herbal remedies and trace elements used as food additives. In: De Broe, M. E., Et Al., Editors. Clinical Nephrotoxins: Renal Injury From Drugs And Chemicals. Dordrecht(Netherlands), Norwell(MA): Kluwer Academic Publishers; 1998. P. 19-423.
BIOSIS COPYRIGHT: BIOL ABS. RRM BOOK CHAPTER HUMAN FOOD ADDITIVES TOXICITY HERBAL REMEDIES TRACE ELEMENTS ACUTE RENAL FAILURE FUMARIC ACID GERMANIUM NEPHROPATHY ANALGESICS TOXICOLOGY NEPHROLOGY EPIDEMIOLOGY CHINESE HERBS UROLOGIC DISEASE DRUG INDUCED AFRICA ETHIOPIAN REGION.

Vanherweghem LJ. Misuse of herbal remedies: the case of an outbreak of terminal renal failure in Belgium (Chinese herbs nephropathy) [see comments]. J Altern Complement Med 1998;4(1):9-13.
At least 100 cases of extensive interstitial fibrosis of the kidneys were observed in Belgium in women who had followed a weight-loss regimen that included the use of Chinese herbs. The possible relation between the renal disease and these Chinese herbs was investigated. It was shown that the prescribed Chinese herb called Stephania tetrandra was, in fact, inadvertently replaced by another Chinese herb, namely Aristolochia fangchi in the powdered extracts delivered in Belgium and in France. The development of renal disease in about 100 patients exposed to the so-called Stephania tetrandra stresses the need for more stringent control of herbal medicine.

Vila L, Sanchez G, Sanz ML, Dieguez I, Martinez A, Palacios R, Martinez J. Study of a case of hypersensitivity to lettuce (Lactuca sativa). Clin Exp Allergy 1998;28(8):1031-5.
BACKGROUND: Allergic reactions to lettuce (Lactuca sativa) are not too frequent and few cases of systemic adverse reactions after its ingestion have been described. OBJECTIVE: We report a case of clinical sensitization to lettuce on a patient who presented mucocutaneous manifestations after its ingestion, with positive skin tests, histamine release test and serum specific-IgE to lettuce. The allergens responsible for this sensitization were also characterized by means of SDS-PAGE immunoblotting. MATERIALS AND METHODS: We performed skin tests, histamine release test, serum specific IgE determination and CAP inhibition with lettuce and mugwort (Artemisia vulgaris) extracts. An aqueous and enriched lettuce (from loose leaf type) extract was subjected to SDS-PAGE immunoblotting for determination of its IgE-binding components. RESULTS AND CONCLUSIONS: CAP inhibition showed antigenic community between lettuce and mugwort. Four protein bands from the lettuce extracts with molecular weights of 50, 43, 39 and 16 kDa exhibited IgE-binding properties.

Violon C. Belgian (Chinese herb) nephropathy: why? J Pharm Belg 1997;52(1):7-27.
During the last years several patients with renal failure were admitted in Brussels hospitals. The progressive interstitial fibrosis with tubular atrophy seen in these patients has been ascribed to the slimming therapy preceding the pathology. The nephropathy was remarkable with regard to its extensive fibrotic process and the rapidity of its evolution. The ingestion of Aristolochia fangchi instead of the prescribed Stephania tetrandra, one of the components of the slimming therapy, was put forward as hypothesis for the etiology of the nephropathies in the literature. Questions however remain unanswered: Why have certain persons, among thousands similarly treated including ingestion of Aristolochic acids, not withstood the treatment? Why is there no correlation between the length of treatment and the occurrence nor the degree of illness? Last but not least: Is it in the actual conditions possible to be confident again in slimming treatments as the concerned one? We made an overview of the pharmacological action and possible (nephro) toxicity of the known components of the concerned therapy. Concerning the Chinese plants we have described and commented on the procedures for quality control actually at disposal and the difficulties in differentiation between resembling species and possible substitute herbs. We have described largely the traditional and medicinal use of the involved Chinese plants as to evaluate their implication in the nephrotoxicity. The elements of the therapy possibly relevant in the etiology of the disease are mentioned. The overview shows that different elements of the therapy are hazardous. Attention is caught to the danger of the use of (Chinese) herbs of unknown origin when nor the indications nor the form of preparation--in this case decoctions--are respected and when the quality cannot be assured, due to lack of (official) operating procedures. Medicinal plants as those implied contain secondary metabolites (bis)-benzylisoquinoline-alkaloids, dihydroxy-diallyl-biphenyls, aristolochic acids) with strong pharmacological (and possibly toxic) actions. Attention is caught to the danger of alternative therapies as mesotherapy. Products are injected which are not proved safe for this administration way. The administration during long periods of cocktails with anorectics (fenfluramine and diethylpropion) in association with a diuretic, a tranquilizer, plants with laxative and atropinergic action are alike to be at the origin of susceptibility in the excretion system. Under these circumstances exposure to any toxic product might cause renal failure. Several years have passed after the scientific reports of the first nephropathy cases in Belgium. We are afraid that prohibiting (temporarily) three Chinese herbs (Stephania tetrandra, Aristolochia fangchi and Magnolia officinalis) does not provide enough safety in order to assume responsibilities for common health care. Keeping in mind that these treatments were not meant to cure any disease but only for slimming, we ask Belgian authorities to regulate strictly the use of (Chinese) herbal medicines, the products and practices in alternative practices as mesotherapy and cocktail-treatments.

Weber KT. Herbs, seeds, oil and eggs: a vasotoxic salad. Cardiovasc Res 1997;34(2):266-7.

Weisbord SD, Soule JB, Kimmel PL. Poison on line--acute renal failure caused by oil of wormwood purchased through the Internet [published erratum appears in N Engl J Med 1997 Nov 13;337(20):1483]. N Engl J Med 1997;337(12):825-7.

Wong ST, Chan HL, Teo SK. The spectrum of cutaneous and internal malignancies in chronic arsenic toxicity. Singapore Med J 1998;39(4):171-3.
We report 3 patients of chronic arsenic poisoning with characteristic skin changes. All 3 patients had a past history of asthma and were treated with Traditional Chinese Medication. We believe that the Chinese medications were the source of arsenic poisoning. Two of the 3 patients also had internal malignancy. The association of arsenic with internal malignancy is reviewed.

Wood B, Rademaker M, Oakley A, Wallace J. Pellagra in a woman using alternative remedies [see comments]. Australas J Dermatol 1998;39(1):42-4.
A young woman presented with pellagra. Dietary intake of niacin was in excess of recommended guidelines. She had a low body mass index and was taking a number of alternative remedies. Resolution was rapid with oral nicotinic acid and discontinuation of the remedies.

Woolley BH. Frequently asked questions about the serotonin syndrome. Utah Pharm Dig 1997 Apr;107:14-5.
IPA COPYRIGHT: ASHP A brief overview of the serotonin syndrome, an iatrogenic condition caused by the additive interaction of multiple serotonergic agonists, is presented, including the symptoms; the foods, drugs, and herbs that are implicated in the syndrome are briefly discussed.

Wright IM. Neonatal effects of maternal consumption of blue cohosh [letter]. J Pediatr 1999;134(3):384-5.

Wu CL, Hsu WH, Chiang CD, Kao CH, Hung DZ, King SL, Deng JF.

Lung injury related to consuming Sauropus androgynus vegetable.

Wuthrich B, Schmid-Grendelmeyer P, Lundberg M. Anaphylaxis to saffron. Allergy 1997;52(4):476-7.
BIOSIS COPYRIGHT: BIOL ABS. RRM CASE STUDY CROCUS-SATIVA HUMAN ADULT PATIENT MALE SAFFRON ANAPHYLAXIS FOOD ALLERGY SCRATCH TEST RAST INHIBITION RADIOALLERGOSORBENT TEST INHIBITION ALLERGY HERBS AND SPICES IMMUNE SYSTEM DISEASE DIAGNOSTIC METHOD.

Yamada Y, Sakoda H, Inoue T, Kubo M, Fushimi H, Minami T, Kaneyama M. [Lead poisoning due to Chinese herbal medication in two patients with non-insulin-dependent diabetes mellitus]. J Jpn Diabetes Soc 1998;41(10):933-6. (Jpn)
BIOSIS COPYRIGHT: BIOL ABS. Lead poisoning due to a side effect of Chinese herbal medication in two patients with non-insulin-dependent diabetes mellitus is reported here. Both patients complained of abdominal pain, severe constipation and insomnia. Laboratory data showed normocytic anemia with reticulocytosis, basophilic stippling in erythrocytes, elevated hemoglobin F level and increased excretion of urinary porphyrin, indicating abnormalities of hemoglobin synthesis. Blood lead level and urinary lead excretion were increased by their own judgement, both patients had taken several non-autorized drugs, one of which, "Zhen qi jiang tang," was thought to be the causative drug containing a high level of lead. Since lead contents in the capsules were distributed over a wide range, and another patient had taken the same drug but did not show symptoms of lead poisoning, it was suggested that some capsules were contaminated with lead. Patients were treated by dimercaprol intramuscularly, and gradually symptoms and data have improved.

Yamashiki M, Nishimura A, Nobori T, Nakabayashi S, Takagi T, Inoue K, Ito M, Matsushita K, Ohtaki H, Kosaka Y. In vitro effects of sho-saiko-to on production of granulocyte colony-stimulating factor by mononuclear cells from patients with chronic hepatitis C. Int J Immunopharmacol 1997;19(7):381-5.
During the past 2 years, drug-induced interstitial pneumonia was reported in 66 Japanese patients, mainly among chronic hepatitis C patients, undergoing treatment with the Japanese herbal medicine "Sho-saiko-to" (TJ-9). As interstitial pneumonia is also induced by granulocyte colony-stimulating factor (G-CSF), we examined the effects of TJ-9 on G-CSF production in peripheral blood mononuclear cells. In patients with hepatitis B or C, G-CSF production in the absence of any stimulation was significantly lower than healthy controls (p < 0.01). G-CSF production increased along with the increase of TJ-9 levels, and this could induce excessive production of G-CSF in hepatitis C patients, and this may be a cause of interstitial pneumonia.

Yang HY, Chen CF. Pharmacology and toxicology of herbal medicine: subacute toxicity of commonly used Chinese drugs. J Toxicol Sci 1998;23(Suppl 2):229-33.

Yang Jiong, Hu Suping, Zhong Lihou, et al . [An investigation into the major allergic pollens in Wuchang district]. Acta Acad Med Hubei 1998;19(1):37-9. (Chi)
BIOSIS COPYRIGHT: BIOL ABS. An preliminary investigation on airborne pollens in Wuchang district showed that platanus, pinus, artemisia is the major pollen. Inraderimed skin test against 13 pollens was done among 210 allergic patients. The results were:positive rate of artemisia is the highest of all, ambrosia next to it. From high to low., the positive rate is humulus, platanus, broussoretia, etc. Pollens allerge concentrated from March to May and August to October especially in the latter. It is suggested that platanus is the main allergic pollen, artemisia, ambrosia, humulus is the main allergic pollen in Summer and Autumn in Wuchang district.

Yeung CY. Changing pattern of neonatal jaundice and kernicterus in Chinese neonates. Chin Med J (Engl) 1997;110(6):448-54.

Yokoi T. [Chinese herbs nephropathy in the Kansai area: a warning report (letter)]. Nippon Jinzo Gakkai Shi 1998;40(5):364-5. (Jpn)

Yoshikubo S, Kimura K, Mizutari K, Kamo S, Maeda K. [A case of drug-induced liver injury due to bukuryo-in-go-hange-koboku-to]. Nippon Shokakibyo Gakkai Zasshi 1997;94(8):564-8. (Jpn)

Yu CM, Chan JC, Sanderson JE. Chinese herbs and warfarin potentiation by 'danshen'. J Intern Med 1997;241(4):337-9.
Drug interactions with warfarin can be dangerous and although common drug interactions are now well recognized those with Chinese herbs are not widely appreciated. 'Danshen' is a herbal medicine often used for various complaints, particularly cardiovascular, in the Chinese community. We report a case of danshen-induced overcoagulation with severe and dangerous abnormalities of clotting in a patient with rheumatic heart disease.

Zahn KA, Li RL, Purssell RA. Cardiovascular toxicity after ingestion of "herbal ecstacy". J Emerg Med 1999;17(2):289-91.
"Herbal Ecstacy" (sic) is an alternative drug of abuse usually containing both ephedrine and caffeine. Our literature search did not reveal any other reported cases of cardiovascular toxicity related to herbal "drugs of abuse." A case of cardiovascular toxicity following the ingestion of herbal ecstacy is presented. A 21-year-old male presented to the emergency department with an initial blood pressure of 220/110 mmHg and ventricular dysrhythmias after ingesting four capsules of herbal ecstacy. He was treated with lidocaine and sodium nitroprusside, and his symptoms resolved in 9 h. The pathophysiology and clinical course of ephedrine toxicity are discussed. Emergency physicians should consider ephedrine preparations in the differential diagnosis of patients presenting with a sympathomimetic toxidrome. Drugs of abuse containing "herbal" products can produce serious morbidity and mortality.

Adegoke GO, Kumar MV, Sambaiah K, Lokesh BR. Inhibitory effect of Garcinia kola on lipid peroxidation in rat liver homogenate. Indian J Exp Biol 1998;36(9):907-10.
Garcinia kola, (a herb grown in Nigeria; calorific value 358.54 k.cal/100 g) inhibited in vitro lipid peroxidation of rat liver homogenate in a dose dependent manner. The inhibitory activity of G.kola was not affected by heating (100 degrees C/10 min). The antioxidant component of G.kola was soluble in aqueous and ethanolic media. The active component(s) in G. kola responsible for its inhibitory activity on lipid peroxidation is tentatively identified as isoflavones.

Ahn YJ, Lee CO, Kweon JH, Ahn JW, Park JH. Growth-inhibitory effects of Galla Rhois-derived tannins on intestinal bacteria. J Appl Microbiol 1998;84(3):439-43.
The growth-inhibitory activity of Galla Rhois-derived materials towards 17 intestinal bacteria was evaluated using an impregnated paper disc method. The biologically active components of Galla Rhois were characterized as the tannins methyl gallate (MG) and gallic acid (GA) by spectral analysis. The growth responses varied with bacterial strain tested. In the test using 10 mg disc-1, MG and GA produced a clear inhibitory effect on harmful bacteria such as Clostridium perfringens, Cl. paraputrificum, Eubacterium limosum, Bacteroides fragilis, Staphylococcus aureus and Escherichia coli. Methyl gallate showed no growth-inhibitory activity towards Bifidobacterium adolescentis or B. longum whereas the growth of B. bifidum, B. breve, B. infantis, B. animalis, B. thermophilum, Lactobacillus acidophilus, Lact. plantarum and Streptococcus faecalis was slightly affected. However, GA did not adversely affect the growth of the bifidobacteria and lactobacilli. At 5 mg disc-1, MG significantly inhibited the growth of Cl. perfringens and Cl. paraputrificum but did not affect the growth of the bifidobacteria and lactobacilli. At 1 mg disc-1, MG greatly inhibited the growth of Cl. perfringens alone. These results may be an indication of at least one of the pharmacological actions of Galla Rhois.

Akamatsu H, Asada Y, Horio T. Effect of keigai-rengyo-to, a Japanese kampo medicine, on neutrophil functions: a possible mechanism of action of keigai-rengyo-to in acne. J Int Med Res 1997;25(5):255-65.
On the basis of recent reports that keigai-rengyo-to (TJ-50), an oral Japanese Kampo (herb) medicine, is clinically effective in treating acne, and that tetracyclines are effective against acne by acting directly as an antioxidant on infiltrated neutrophils, we investigated the effect of TJ-50 on the generation of reactive oxygen species (ROS), using human neutrophils and a cell-free, xanthine-xanthine oxidase system. The species investigated were superoxide radical anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH.). In addition, neutrophil chemotaxis, phagocytosis and calcium concentration, [Ca2+]i in neutrophils were also assessed. TJ-50 significantly decreased neutrophil-generated O2-, H2O2 and OH. in a dose-dependent manner. Three kinds of ROS generated in the cell-free system were also reduced in the presence of TJ-50. On the other hand, the medicine did not markedly affect neutrophil chemotaxis, phagocytosis or [Ca2+]i in neutrophils. Our results indicate that the clinical effectiveness of TJ-50 in the treatment of acne may be due partly to its antioxidant action on infiltrated neutrophils.

Arai I, Komatsu Y, Hirai Y, Shingu K, Ida Y, Yamaura H, Yamamoto T, Kuroiwa Y, Sasaki K, Taguchi S. Stimulative effects of saponin from kikyo-to, a Japanese herbal medicine, on pancreatic exocrine secretion of conscious rats. Planta Med 1997;63(5):419-24.
Our previous report stated that kikyo-to, a Japanese herbal medicine, consisting of the roots of Platycodon grandiflorum and Glycyrrhiza sp., stimulates the pancreatic exocrine secretion of conscious rats. The present study focused on the effective components of kikyo-to and the mechanism of stimuli to pancreatic secretion of rats. When 10 to 100 mg of platycodin D, a saponin from the root of Platycodon grandiflorum, was intragastrically administered, the pancreatic secretion of rats was stimulated. At the same time, the plasma CCK concentration increased. On the other hand, the stimulative effects of glycyrrhizin, a saponin from the root of Glycyrrhiza sp. were weak compared to platycodin D. The effects of 10 mg/kg of platycodin D on pancreatic secretion were inhibited by loxiglumide (50 mg/kg, i.g.), a CCK receptor antagonist. In contrast, the suppressive effect of atropine (300 micrograms/kg/h, i.v.) on pancreatic secretion was reduced by administering 10 mg/kg of platycodin D. In addition, up to 1 mM of platycodin D did not inhibit the trypsin activities in vitro. In conclusion, kikyo-to serves to stimulate pancreatic exocrine secretion mainly because platycodin D causes gastrointestinal hormones, particularly, CCK to be released from the duodenum.

Asano K, Matsuishi J, Yu Y, Nemoto K, Nakazawa M, Kasahara T, Hisamitsu T. Suppressive activity of the chloroform extract of Tripterygium wilfordii Hook f on effector T cell activation during Hymenolepis nana infection in mice. Am J Chin Med 1998;26(2):181-9.
The chloroform extract of Tripterygium wilfordii Hook f (TWH extract) administered into mice daily at doses of 80.0 to 200.0 micrograms/kg (but not 40.0 micrograms/kg) caused suppression of protective immunity to Hymenolepis nana when the extract was injected subcutaneously during the induction phase of protective immunity. Daily administration of 200.0 micrograms/kg TWH extract, during the course of larval development from challenge, also suppressed protective immunity. Inhibition of protective immunity was only observed in mice that received TWH extract for 6 days at a daily dose of 200.0 micrograms/kg and were challenged 24 h after the final injection. TWH extract did not inhibit formation of effector cells that mediate delayed type hypersensitivity (DTH) to H. nana egg antigen when the extract was administered subcutaneously at a dose of 200.0 micrograms/kg/day for 5 days before cell preparation. However, TWH extract did inhibit DTH effector cell activation when cells prepared from infected, PBS-injected mice were transferred into 200.0 micrograms/kg TWH extract-treated recipient mice. These results strongly indicate that TWH extract cannot inhibit the generation of effector cells but will suppress their function in vivo.

Bae EA, Han MJ, Kim NJ, Kim DH. Anti-Helicobacter pylori activity of herbal medicines. Biol Pharm Bull 1998;219(9):990-2.

Bennett DA Jr, Phun L, Polk JF, Voglino SA, Zlotnik V, Raffa RB. Neuropharmacology of St. John's Wort (Hypericum). Ann Pharmacother 1998;32(11):1201-8.
OBJECTIVE: To review preclinical information related to possible antidepressant mechanism(s) of action of St. John's wort in order to address the issue of whether its purported clinical effectiveness has a rational pharmacologic basis. DATA SOURCES: Primary and review articles were identified by a MEDLINE search (1966-January 1998) and through secondary sources. Many of the original German articles had English abstracts, but where necessary, German articles were translated into English. The results of a new screen of hypericin activity at receptor and uptake sites are summarized. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated and all information deemed relevant was included in this review. DATA SYNTHESIS: The neuropharmacology of St. John's wort has been examined in only a few studies. A mechanism similar to that of the synthetic antidepressants, such as the selective serotonin-reuptake inhibitors or monoamine oxidase (MAO) inhibitors, might play a role, but other mechanisms are possible. CONCLUSIONS: Hypericum extracts have only weak activity in assays related to mechanisms of the synthetic antidepressants, that is, inhibition of MAO, catechol O-methyltransferase, or serotonin reuptake. It has been postulated that the clinical efficacy of St. John's wort could be attributable to the combined contribution of several mechanisms, each one too weak by itself to account for the overall effect. The recent demonstration of a significant affinity of hypericin for sigma receptors presents new possibilities for consideration.

Bork PM, Schmitz ML, Kuhnt M, Escher C, Heinrich M. Sesquiterpene lactone containing Mexican Indian medicinal plants and pure sesquiterpene lactones as potent inhibitors of transcription factor NF-kappaB. FEBS Lett 1997;402(1):85-90.
The potential inhibitory effect of 54 Mexican Indian medicinal plants on the activation of transcription factor NF-kappaB was studied. Band-shift experiments identified the ethanolic leaf extracts of Artemisia ludoviciana ssp. mexicana, Calea zacatechichi, and Polymnia maculata (all rich in sesquiterpene lactones) as inhibitors of NF-kappaB down to a concentration of 25 microg/ml. The sesquiterpene lactones isohelenin and parthenolide prevented NF-kappaB activation completely as low as 5 microM. Treatment of HeLa cells with leaf extract of A. ludoviciana ssp. mexicana, isohelenin and parthenolide prevented the induction of transcription on the IL-6 promoter. These experiments identify the eudesmanolide and germacranolide type of sesquiterpene lactones as potent non-antioxidant inhibitors of NF-kappaB. All plants active in the NF-kappaB assay also showed a delay in the onset of capillary reactions of the allantois membrane in a physiological model for anti-inflammatory activity - the HET-CAM assay.

Burger RA, Torres AR, Warren RP, Caldwell VD, Hughes BG. Echinacea-induced cytokine production by human macrophages. Int J Immunopharmacol 1997;19(7):371-9.
Echinacea purpurea, a plant originally used by native Americans to treat respiratory infections, was evaluated for its ability to stimulate the production of cytokines by normal human peripheral blood macrophages in vitro. Commercial preparations of echinacea fresh pressed juice and dried juice were tested at concentrations ranging from 10 micrograms/ml to 0.012 microgram/ml and compared to endotoxin stimulated and unstimulated controls. Cytokine production was measured by ELISA after 18 h of incubation for IL-1 and 36 and 72 h for TNF-alpha, IL-6, and IL-10. Macrophages cultured in concentrations of echinacea as low as 0.012 microgram/ml produced significantly higher levels of IL-1, TNF-alpha, IL-6 and IL-10 (P < 0.05) than unstimulated cells. The high levels of IL-1, TNF-alpha, and IL-10 induced by very low levels of echinacea are consistent with an immune activated antiviral effect. Echinacea induced lower levels of IL-6 in comparison to the other cytokines measured. These results demonstrate the immune stimulatory ability of the unpurified fresh pressed juice of Echinacea purpurea and offer some insight into the nature of the resulting immune response as compared to endotoxin.

Caballero T, Pascual C, Garcia-Ara MC, Ojeda JA, Martin-Esteban M. IgE crossreactivity between mugwort pollen (Artemisia vulgaris) and hazelnut (Abellana nux) in sera from patients with sensitivity to both extracts. Clin Exper Allergy 1997;27(10):1203-11.
BIOSIS COPYRIGHT: BIOL ABS. Background. An association between sensitization to Compositae pollens and hypersensitivity to hazelnut has been previously described. There is no previous in vitro study about crossreactivity between mugwort pollen and hazelnut. Objectives. To study mugwort pollen and hazelnut allergens and to assess if there is IgE crossreactivity between mugwort pollen and hazelnut. Methods. A serum pool formed by 28 individual sera with specific IgE to mugwort pollen and hazelnut was used to investigate IgE crossreactivity. RAST-inhibition, SDS-PAGE/IEF immunoblotting inhibition assays were performed by preincubation of the sera with mugwort pollen and hazelnut. Results. RAST to hazelnut was inhibited up to 63% by mugwort pollen, but the mugwort pollen RAST was only inhibited up to 36% by hazelnut. In SDS-PAGE immunoblotting mugwort pollen showed nine allergens ranging from <16 to 65 kDa and hazelnut had four main allergens: 42 kDa, 17 kDa and <16 kDa (two bands). In the SDS-PAGE immunoblotting inhibition hazelnut partially inhibited all the mugwort pollen bands, except that with 19 Kda, whereas mugwort pollen produced a nearly total inhibition of all the hazelnut allergens. In isoelectrofocusing immunoblotting mugwort pollen had two groups of allergens: Pi 7.5-8.5 and Pi 3.5-5.2 and hazelnut one group of allergens: Pi 5.2-5.8. In the isoelectrofocusing immunoblotting inhibition hazelnut produced a partial inhibition of all the bands of mugwort pollen and mugwort pollen partially inhibited all the allergenic bands of hazelnut. Conclusions. The RAST and SDS-PAGE/IEF immunoblotting inhibition results provide evidence of IgE cross reactivity between mugwort pollen and hazelnut allergens. The inhibition of hazelnut by mugwort pollen is higher than the inhibition of mugwort pollen by hazelnut in both RAST inhibition and SDS-PAGE immunoblotting inhibition. These results suggest that mugwort pollen allergens would behave as primary immunogens in the association between sensitivity to mugwort pollen and hazelnut.

Carlson M, Thompson RD. Liquid chromatographic determination of methylxanthines and catechins in herbal preparations containing guarana. J AOAC Int 1998;81(4):691-701.
Herbal preparations derived from the dried seeds of guarana (Paullinia cupana) have become a popular nutritional supplement used for stimulatory purposes. Once considered a drug substance in the United States, guarana currently is classified as a food additive and dietary supplement. The pharmacological activity of guarana-containing products is primarily due to methylxanthine alkaloids. For guarana preparations, methylxanthine levels and, more significantly, the presence of several polyphenol compounds (i.e., catechins) provide phytochemical markers of authenticity. Methylxanthines and polyphenols are extracted from sample matrix with a heated phosphate buffer-methanol solution, the cooled extract is filtered, and the extract is injected into the liquid chromatographic (LC) system. A Nova-Pak C18 column eluted with phosphate buffer-methanol mobile phase (pH = 3.50) and monitored at 272 nm gave satisfactory resolution for the methylxanthines theobromine, theophylline, caffeine and the polyphenols (+)-catechin and (-)-epicatechin. Twenty-four products including dried seeds, dried paste, seed powders, tablets, and capsule formulations were assayed and conclusions were drawn about their authenticity. The LC system responded linearly to methylxanthines over the 100-fold range in concentration from 0.043 to 4.30 micrograms/mL for theobromine and caffeine and from 0.041 to 4.10 micrograms/mL for theophylline. Precision data for the 3 methylxanthines obtained from 10 different products (n = 5) gave relative standard deviation (RSD) values of 1.18-15.52% within a concentration range of 0.01-52.28 mg/g. Recoveries of methylxanthines from fortified products varied from 87.5 to 120.0%. The response for catechins was linear over a 200-fold range in concentration of 0.05-10.0 micrograms/mL. Precision data from 5 products (n = 5) gave RSD values of 1.08-5.54% within a concentration range of 0.34-32.65 mg/g. Recoveries from these products ranged from 87.7 to 109.7%. Results and chromatographic profiles for 14 commercial products in solid dosage form indicate that a number of these products may not contain authentic guarana as an active ingredient or contain less than the declared quantity of guarana. The proposed procedure also was applied to 2 carbonated soft drinks and a sample of mate.

Chaumontet C, Droumaguet C, Bex V, Heberden C, Gaillard-Sanchez I, Martel P. Flavonoids (apigenin, tangeretin) counteract tumor promoter-induced inhibition of intercellular communication of rat liver epithelial cells. Cancer Lett 1997;114(1-2):207-10.
We have shown previously that two flavonoids, apigenin and tangeretin, enhance gap junctional intercellular communication (GJIC) in rat liver epithelial cells, named REL cells. Here, we show that these two flavones also antagonize the inhibition of GJIC induced by tumor promoters like 12-O-tetradecanoyl-phorbol-acetate (TPA) and 3,5,di-tertio-butyl-4-hydroxytoluene (BHT). Their preventive effect is rapid. It does not seem to involve any change of the amount of the connexin expressed in REL cells, connexin 43 (Cx 43), and in its phosphorylation state. Other flavonoids tested including naringenin, myricetin, catechin and chrysin did not enhance GJIC nor counteract TPA-induced inhibition of GJIC.

Chavali SR, Weeks CE, Zhong WW, Forse RA. Increased production of TNF-alpha and decreased levels of dienoic eicosanoids, IL-6 and IL-10 in mice fed menhaden oil and juniper oil diets in response to an intraperitoneal lethal dose of LPS. Prostaglandins Leukot Essent Fatty Acids 1998;59(2):89-93.
Eicosapentaenoic acid (EPA) and the non-methylene interrupted fatty acids (NMIFA) displace arachidonic acid (AA: 20:4omega6 -5,8,11,14) in the membrane phospholipids. Unlike EPA (20:5omega3 -5,8,11,14,17), the NMIFA (20:3omega6 -5,11,14 and 20:4omega3 -5,11,14,17) lacking the delta-8 double bond are not substrates for the formation of eicosanoids. For 20 days, the mice were fed diets containing 5wt% dietary fats from various sources. The magnitudes in the production of eicosanoids and cytokines produced in response to an intraperitoneal injection of endotoxin in mice fed menhaden fish oil (MO) diets enriched with EPA were compared with those maintained on juniper oil (JO) containing NMIFA or on safflower oil (SO), a major source of the AA precursor, linoleic acid. The levels of PGE2, 6-keto-PGF1alpha and TXB2 were markedly lower (P < 0.01) in animals fed either MO or JO diets compared to the controls. The plasma levels of tumor necrosis factor (TNF)-alpha were significantly higher (P < 0.05) with a concomitant decrease of interleukin (IL)-6 and of IL-10 in mice fed MO or JO diets (P < 0.01) compared to those fed SO diet. These data suggest that the effects of consuming NMIFA of JO despite their inability to form eicosanoids are similar to those of feeding EPA which forms biologically active alternate metabolites.

Chen L, Hong JY, So E, Hussin AH, Cheng WF, Yang CS. Decrease of hepatic catalase level by treatment with diallyl sulfide and garlic homogenates in rats and mice. J Biochem Mol Toxicol 1999;13(3-4):127-34.
Diallyl sulfide (DAS) is a flavor compound derived from garlic and is active in the inhibition of chemically induced cytotoxicity and carcinogenicity in animal models. This study was conducted to examine the effects of the treatment of DAS and garlic homogenates on the activities of catalase, glutathione peroxidase, and superoxide dismutase. Male Sprague-Dawley rats were treated with DAS i.g. at daily doses of 50 or 200 mg/kg for 8 days, causing the hepatic catalase activity to decrease by 55 and 95%, respectively. Such a decrease in hepatic catalase activity was also observed when the DAS treatment was extended to 29 days. Western blot analysis showed that the DAS treatments resulted in corresponding decreases in the liver catalase protein level. No significant change in the catalase activity in the kidney, lung, and brain was observed with the treatments, but a slight decrease in heart catalase activity was observed. These treatments did not cause significant changes in superoxide dismutase and glutathione peroxidase activities in these tissues. Treatment with DAS at a daily dose of 200 mg/kg for 1-7 days resulted in a gradual decrease in the liver catalase activity to 5% of the control level, but it did not decrease the erythrocyte catalase activity. Treatment of rats with fresh garlic homogenates (2 or 4 g/kg, i.g., daily for 7 days) caused a 35% decrease in liver catalase activity. A/J mice treated with DAS and garlic homogenates also showed a decrease in the liver catalase activity. Diallyl sulfone (DASO2), a DAS metabolite, however, did not effectively decrease catalase activity in mice. The catalase activity was not inhibited by either DAS or DASO2 in vitro. The present results demonstrate that treatment with DAS and garlic homogenates decrease the hepatic catalase level in rats and mice.

Chiu KW, Fung AY. The cardiovascular effects of green beans (Phaseolus aureus), common rue (Ruta graveolens), and kelp (Laminaria japonica) in rats. Gen Pharmacol 1997;29(5):859-62.
1. The hypotensive effect of green beans, common rue and kelp was recently shown in normotensive rats in vivo. A number of mechanisms of action of these aqueous extracts was identified. The present study examined these actions at the tissue level in vitro with possible interactions of these extracts. 2. Rue showed positive chronotropic and inotropic effects on isolated right atria. Green beans and kelp alone showed negative chronotropic effects on isolated right atria but no effect on atrial tension (AT). A combination of green beans and kelp showed no additive effect on the decrease in atrial rate (AR) nor any negative inotropic responses. Combinations of rue and green beans and of rue and kelp showed responses that were either positive or negative chronotropically, were not dose dependent and were less than the sum total of their individual responses (i.e., subtractive). A combination of all three showed subtractive effects on the decrease in AR that were dose related. No change in AT was observed upon treatment with a combination of the three plant extracts in spite of the positive inotropic effect of true. 3. Rue and kelp alone relaxed KCl preconstricted rat tail artery strips probably by a direct effect of vascular smooth muscle. Green beans had no effect. The combination of rue and kelp exerted a subtractive relaxation effect. These plants therefore contained cardiovascular active substances that had a direct effect on the cardiovascular system. These substances further interacted to modify their cardiovascular effects. 4. Data explained why herbs, as in herbal medicine, should be used together therapeutically.

Choudhury AR, Das T, Sharma A. Mustard oil and garlic extract as inhibitors of sodium arsenite-induced chromosomal breaks in vivo. Cancer Lett 1997;121(1):45-52.
Arsenic, a well-known human carcinogen present as a contaminant in ground water poses a serious threat to public health in various countries. The anticlastogenic properties of two dietary supplements, garlic and mustard oil, were screened against the clastogenic activity of sodium arsenite, since diet may contain factors which affect the process of mutagenesis and carcinogenesis. Aqueous extract of garlic (100 mg/kg b.w.) and mustard oil (0.643 mg/kg b.w.) were fed to Mus musculus for 30 consecutive days either singly or simultaneously. Sodium arsenite (0.1 mg/kg b.w.) was injected subcutaneously on days 7, 14, 21 and 30 of the experiment, singly and together with the dietary supplements. The animals were sacrificed 24 h after the last exposure to sodium arsenite and clastogenic effects were observed in the bone marrow cells. The degree of modulation of sodium arsenite-induced chromosomal aberrations was more pronounced in mustard oil than in garlic extract and simultaneous administration of both the dietary supplements reduced the clastogenic effects of sodium arsenite closer to the level of the negative control. The greater efficacy could be due to the interaction of the two dietary supplements and its radical scavenging property.

Choudhury AR, Das T, Sharma A, Talukder G. Inhibition of clastogenic effects of arsenic through continued oral administration of garlic extract in mice in vivo. Mutat Res 1997;392(3):237-42.
Crude aqueous extract of garlic bulbs (Allium sativum L. single clove variety) was administered by gavage to mice of both sexes daily for up to 30 and 60 days, in doses corresponding to 6 g for a 60 kg human body. Sodium arsenite (at 1/50 of LD50 dose) was injected subcutaneously to mice on every 7th day of the experiment. Chromosome preparations made from bone marrow following flame drying Giemsa schedule were screened for chromosomal aberrations. The clastogenic affects of prolonged exposure to sodium arsenite --a strong clastogen-- was reduced by a highly significant amount when crude garlic extract, in the dose used, was given daily to the mice by intubation for the same period.

Chu TC, Han P, Han G, Potter DE. Intraocular pressure lowering by S-allylmercaptocysteine in rabbits. J Ocul Pharmacol Ther 1999;15(1):9-17.
The purpose of this study was to examine the actions of a garlic-derived compound, S-allylmercaptocysteine (SAMC) on intraocular pressure (IOP) and to determine the possible involvement of sulfhydryl reactivity, sympathetic neuronal activity and atrial natriuretic peptide (ANP) in the IOP response. Topical, unilateral application of SAMC (20, 100, 200 microg) elicited dose-dependent decreases in IOP. The magnitude of the IOP-lowering effect induced by SAMC was between four to six mmHg. The ocular hypotensive responses were unilateral, peaked at one to three hours and lasted from two to four hours. The IOP-lowering effect by SAMC (100 microg) was enhanced modestly by topical, bilateral pretreatment with a reducing agent, tris(2-carboxyethyl) phosphine (100 microg) which itself produced no change in IOP. No alteration of pupil diameter was observed following topical application of either SAMC or tris(2-carboxyethyl) phosphine. Thus, alteration of sulfhydryl reactivity does not seem to be a major mechanism of action for SAMC. SAMC caused no change of basal and electrically stimulated norepinephrine release in rabbit iris-ciliary bodies, ruling out a prejunctional effect on sympathetic nerve activity. However, SAMC increased the ANP levels in aqueous humor by five-fold. It is concluded that the ocular hypotensive response induced by SAMC in rabbits could involve the elevation of ANP levels in aqueous humor.

Chung E, Lee KY, Lee YJ, Lee YH, Lee SK. Ginsenoside Rg1 down-regulates glucocorticoid receptor and displays synergistic effects with cAMP. Steroids 1998;63(7-8):421-4.
Ginsenoside-Rg1 (G-Rg1) from the roots of Panax ginseng C. A. Meyer has been shown to bind to the glucocorticoid receptor (GR). To further explore the effect of G-Rg1 binding to GR, a luciferase reporter gene containing two copies of a glucocorticoid response element was constructed and transiently transfected into FTO2B rat hepatoma cells. A dose-dependent induction of the reporter gene was observed in response to G-Rg1, and the inductive effect was blocked by treatment with the antiglucocorticoid RU486. In addition, both G-Rg1- and dexamethasone (Dex)-induced transcription was synergistically enhanced by the treatment of dibutyryl cAMP (Bt2-cAMP). G-Rg1 treatment also led to the down-regulation of intracellular GR content, which was similar to the effect of Dex. By showing that G-Rg1 down-regulates GR and induces GR-mediated transcription synergistically with cAMP, we conclude that G-Rg1 is a functional GR ligand in FTO2B cells.

Coulombe RA Jr, Drew GL, Stermitz FR. Pyrrolizidine alkaloids crosslink DNA with actin. Toxicol Appl Pharmacol 1999;154(2):198-202.
Pyrrolizidine alkaloids (PAs) are toxic constituents of hundreds of plant species, some of which people are exposed to in herbal products and traditional remedies. The bioactivity of PAs are related, at least in part, to their ability to form DNA-protein complexes (DPC). Previous studies from our laboratory indicated a possible role for actin in PA-induced DPCs. Nuclei prepared from Madin-Darby bovine kidney (MDBK) and human breast carcinoma (MCF-7) cells were treated with the pyrrolic PAs dehydrosenecionine (DHSN) and dehydromonocrotaline (DHMO). DPCs were purified and then analyzed by Western immunoblotting. Actin was found in DPCs induced by both DHSN and DHMO, but not in those from control nuclei. Actin was also present in DPCs induced by cisplatinum and mitomycin C, two bifunctional cross-linkers. In separate experiments, DHSN and DHMO were crosslinked to a mixture of HindIII digested lambda phage with varying amounts of glutathione (GSH), cysteine, or methionine to identify the stoichiometry of competition between DNA and alternate nucleophiles for crosslink formation with pyrroles. GSH and cysteine, but not methionine, competed with lambda phage for DNA crosslinking, indicating that reduced thiols may have a role in nucleophilic reactions with pyrroles in the cell. While actin involvement in cisplatinum-induced DPCs is documented, the discovery of actin crosslinking in PA or mitomycin C-treated cells or nuclei is, to our knowledge, novel. Pyrrole-induced DPC formation with actin, a protein with structural and/or regulatory importance proteins, may be a significant mechanism for PA toxicity and bioactivity. Copyright 1999 Academic Press.

Cullen WJ, Dulchavsky SA, Devasagayam TP, Venkataraman BV, Dutta S. Effect of Maharishi AK-4 on H2O2 induced oxidative stress in isolated rat hearts. J Ethnopharmacol 1997;56(3):215-22.
IPA COPYRIGHT: ASHP The ability of the Ayurvedic herbal food supplement Maharishi Amrit Kalash (MAK-4) to decrease oxidative damage in potassium-arrested isolated rat hearts was examined, using hydrogen peroxide as a model pro-oxidant to induce oxidative stress. MAK-4 decreased oxidative stress in terms of release of lactate dehydrogenase and glutathione and as assessed by measuring developed contractile tension. In vitro studies showed that MAK-4 contains hydrogen peroxide binding activity that resulted in the decreased availability of hydrogen peroxide itself. It was concluded that the food supplement MAK-4 may have potential benefits in reducing oxidative stress.

Cupp MJ. Herbal remedies: adverse effects and drug interactions. Am Fam Physician 1999;59(5):1239-45.
A growing number of Americans are using herbal products for preventive and therapeutic purposes. The manufacturers of these products are not required to submit proof of safety and efficacy to the U.S. Food and Drug Administration before marketing. For this reason, the adverse effects and drug interactions associated with herbal remedies are largely unknown. Ginkgo biloba extract, advertised as improving cognitive functioning, has been reported to cause spontaneous bleeding, and it may interact with anticoagulants and antiplatelet agents. St. John's wort, promoted as a treatment for depression, may have monoamine oxidase-inhibiting effects or may cause increased levels of serotonin, dopamine and norepinephrine. Although St. John's wort probably does not interact with foods that contain tyramine, it should not be used with prescription antidepressants. Ephedrine-containing herbal products have been associated with adverse cardiovascular events, seizures and even death. Ginseng, widely used for its purported physical and mental effects, is generally well tolerated, but it has been implicated as a cause of decreased response to warfarin. Physicians must be alert for adverse effects and drug interactions associated with herbal remedies, and they should ask all patients about the use of these products.

Denke A, Schneider W, Elstner EF. Biochemical activities of extracts from Hypericum perforatum L. 2nd Communication: inhibition of metenkephaline- and tyrosine-dimerization. Arzneimittelforschung 1999;49(2):109-14.
Extracts from the herb "St. John's wort" (Hypericum perforatum L.), besides other activities such as wound healing, antigout, antirheumatic and diuretic properties, are widely used to counteract neurological disorders such as depressive situations, nervousness and sleeplessness. The characteristic and leading component in these extracts, the dianthraquinone hypericin, is very likely not to represent the main active principle mediating the desirable effects. Thus, standardization of the drug is no longer based on the quantification of total hypericin and since several years simply the determination of dry matter content is in use instead. As biochemical background of depression the lack of catecholamine neurotransmitters or decreased beta-endorphins such as methionine- or leucine-enkephalins have to be envisaged. This communication reports on the inhibition of myeloperoxidase-catalyzed dimerization of enkephalins by Hypericum extracts. The substitution for enkephalins by tyrosine and for myeloperoxidase by horseradish peroxidase may represent a simple and inexpensive biochemical model reaction of pathological events during the manifestation of depressive events suitable for drug standardization.

Dhuley JN. Effect of some Indian herbs on macrophage functions in ochratoxin A treated mice. J Ethnopharmacol 1997;58(1):15-20.
The effect of Indian herbs namely, Asparagus racemosus, Tinospora cordifolia, Withania somnifera and Picrorhiza kurrooa on the functions of macrophages obtained from mice treated with the carcinogen ochratoxin A (OTA) was investigated. The chemotactic activity of murine macrophages was significantly decreased by 17 weeks of treatment with OTA compared with controls. Production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) was also markedly reduced. Treatment with Asparagus racemosus, Tinospora cordifolia, Withania somnifera and Picrorhiza kurrooa significantly inhibited OTA-induced suppression of chemotactic activity and production of IL-1 and TNF-alpha by macropahges. Moreover, we found that Withania somnifera treated macrophage chemotaxis and that Asparagus racemosus induced excess production of TNF-alpha when compared with controls.

Diel F, Detscher M, Borck H, Schrimpf D, Diel E, Hoppe HW. Effects of permethrin on human basophils and lymphocytes in vitro. Inflamm Res 1998;47(Suppl 1):11-2.

Dimpfel W, Schober F, Mannel M. Effects of a methanolic extract and a hyperforin-enriched CO2 extract of St. John's Wort (Hypericum perforatum) on intracerebral field potentials in the freely moving rat (Tele-Stereo-EEG). Pharmacopsychiatry 1998;31(Suppl 1):30-5.
Two extracts of St. John's Wort (Hypericum perforatum) were investigated in the animal model "Tele-Stereo-EEG" which consisted of continuous recording of intracerebral field potentials in the freely moving rat. One was a CO2 extract for research purposes containing 30.14% hyperforin, a phloroglucine derivative known to occur within the reproductive parts of the plant, and lacking other major constituents like naphtodianthrones and flavonoids according to HPLC fingerprint. The other extract was the methanolic extract LI 160S (4.67% hyperforin). The dosage schedule was elaborated for the application of identical amounts of hyperforin in both extracts in each dosing group. Both extracts produced nearly identical patterns of electrical power changes during the first two hours of recording. These changes mainly consisted of reproducible power increases within the alpha1 band of the striatum. Comparison with earlier data obtained by identical protocols revealed that the early action was very similar to that following the application of serotonin reuptake inhibitors, thus matching biochemical in vitro data previously reported. These changes might be due to the presence of hyperforin. Only LI 160S developed a late action not seen with the CO2 extract, consisting in increases in delta activity. This late action of LI 160S matched data obtained by analysis of the action of NMDA-antagonists like MK 801 or memantine. Again, these results support previously reported biochemical findings of the interaction of hypericum extract with the glutamatergic system. In all probability, this action stems from substances only present in LI 160S, not in the CO2 extract. Which of the components contained within hypericum extracts are responsible for the clinical efficacy of St. John's wort in depression remains to be determined.

Dong Y, Yang MM, Kwan CY. In vitro inhibition of proliferation of HL-60 cells by tetrandrine and coriolus versicolor peptide derived from Chinese medicinal herbs. Life Sci 1997;60(8):135-40.
Coriolus versicolor polysaccharide peptide (CVP) and the bis-benzylisoquinoline alkaloids, tetrandrine (TET) and berbamine (BER), the active ingredients isolated from Chinese medicinal herbs known to possess antitumor activities, concentration-dependently inhibited the proliferation of human leukemic HL-60 cells. CVP did not affect the growth of normal human peripheral blood lymphocytes (PBL), whereas TET elicited concentration-dependent cytotoxic effects. Morphological observation and DNA analysis revealed that CVP elicited no effect on the morphological features of HL-60 cells and did not cause DNA fragmentation, but TET and BER caused cell shrinkage with the formation of apoptotic bodies, and showed clear evidence of DNA fragmentation. These findings indicate that TET and BER, but not CVP, inhibited the proliferation of HL-60 cells via induction of apoptosis.

Dres C, Johnson C, Lods L, Scholz D, Brooks G. Enzymes and erythema reduction. Soap Perfum Cosmet 1998 Mar;71:31, 33.
IPA COPYRIGHT: ASHP In vitro and in vivo studies of the effects of a stabilized copper and zinc yeast derived superoxide dismutase with antioxidant properties and peroxidase extracted from Foeniculum vulgare (fennel) on UV induced erythema are described. It was noted that the studies indicated that superoxide dismutase prevents the synthesis of prostaglandin E2 and thus decreases visible erythema levels. A study conducted in 12 subjects (ages 24-40 yr) who applied various antioxidants showed an overall 47.9% reduction in UV B induced erythema with superoxide dismutase. The efficacy of the peroxidase extract was demonstrated in 2 studies. The first study showed the ability of fennel extract to consistently inhibit lipid peroxidation. It also reduced UV induced erythema. The results of the second study showed a 65% reduction in UV induced erythema.

Dwivedi C, John LM, Schmidt DS, Engineer FN. Effects of oil-soluble organosulfur compounds from garlic on doxorubicin-induced lipid peroxidation. Anticancer Drugs 1998;9(3):291-4.
Clinical efficacy of doxorubicin is compromised due to free radical generation leading to cardiac toxicity. Oil-soluble organosulfur compounds, diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), present in garlic were examined for their antiperoxidant effects. DADS inhibited liver microsomal lipid peroxidation induced by NADPH, ascorbate and doxorubicin. DAS, DPS and DPDS were ineffective inhibitors of liver microsomal lipid peroxidation. DADS could be used in combination with doxorubicin to protect oxidative injuries to improve the clinical efficacy of doxorubicin.

Espinola EB, Dias RF, Mattei R, Carlini EA. Pharmacological activity of Guarana (Paullinia cupana Mart.) in laboratory animals. J Ethnopharmacol 1997;55(3):223-9.
Mice that ingested a suspension of guarana (Paullinia cupana, Sapindaceae) in a dose of 0.3 mg/ml showed a significant increase in physical capacity when subjected to a stressful situation such as forced swimming after 100 and 200 days of treatment. Such an effect, however, was not obtained with a concentration of 3.0 mg/ml, nor with the ingestion of a suspension of ginseng 5.0 mg/ml, nor of a solution of caffeine 0.1 mg/ml. Guarana, both after a single (3.0 and 30 mg/kg) or chronic administrations (0.3 mg/ml), was able to partially reverse the amnesic effect of scopolamine as measured through a passive avoidance test in mice and rats, indicating a positive effect on memory acquisition. However, no effect was observed when an active avoidance task was used in rats, even after 20 days of guarana administration. There was also a tendency of rats treated with 0.3 mg/ml of guarana to better maintain the memory of a Lashley III maze path. The animals had the same average lifespan, indicating a low toxicity of guarana, even after 23 months of treatment.

Fan YC, Lu R, Lu YZ. [Effect of xinfukang on lipid peroxidation and membrane fluidity in myocardial cells of suckling mice incubated in vitro]. Chin Tradit Herb Drugs 1997 Sep;28:545-7. (Chi)
IPA COPYRIGHT: ASHP The effect of xinfukang, a Chinese herbal preparation, on lipid peroxidation and membrane fluidity in myocardial cells of suckling mice incubated in vitro was investigated. Xinfukang decreased lipid peroxidation and improved membrane fluidity in mouse hypoxic myocardial cells.

Fejes S, Kery A, Blazovics A, Lugasi A, Szoke E, et al . [Investigation of the in vitro antioxidant effect of Petroselinum crispum (Mill.) Nym. ex A. W. Hill]. Acta Pharm Hung 1998;68(3):150-6. (Hun)

Geng Z, Rong Y, Lau BH. S-allyl cysteine inhibits activation of nuclear factor kappa B in human T cells. Free Radic Biol Med 1997;23(2):345-50.
Reactive oxygen species are involved in signal transduction pathways leading to nuclear factor kappa B (NF-kappa B) activation which has been implicated in the regulation of gene transcription. We recently reported that a garlic compound, S-allyl cysteine (SAC), protects bovine pulmonary artery endothelial cells from oxidant injury induced by hydrogen peroxide (H2O2). In this study we determined the effects of SAC on NF-kappa B activation in human T lymphocytes (Jurkat cells) induced by tumor necrosis factor alpha (TNF- alpha) and H2O2. Activated NF-kappa B in nuclear extracts was measured by an electrophoretic mobility shift assay using 32P-labeled probe. SAC consistently exhibited a dose-dependent inhibition of NF-kappa B activation induced by both TNF-alpha and H2O2. Supershift with specific antibodies to NF-kappa B subunits confirmed that the inducible retarded bands observed in the EMSA and p65-p50 heterodimer of the NF-kappa B/Rel protein. Our data suggest that SAC may act via antioxidant mechanisms to block NF-kappa B activation in Jurkat cells.

Gleitz J, Beile A, Wilkens P, Ameri A, Peters T. Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human platelets. Planta Med 1997;63(1):27-30.
(+)-Kavain, a 4-methoxy-alpha-pyrone prepared from Piper methysticum Forst. (Piperaceae), was investigated regarding its assumed antithrombotic action on human platelets which was deduced from its ability to suppress arachidonic acid (AA)-induced aggregation, exocytosis of ATP, and inhibition of cyclooxygenase (COX) and thromboxane synthase (TXS) activity, the latter two effects being estimated from the generation of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), respectively. Exogenously applied AA (100 mumol/l) provoked a 90% aggregation of platelets, the release of 14 pmol ATP, and the formation of either 220 pg TXA2 or 43 pg PGE2, each parameter being related to 10(6) platelets. An application of (+)-kavain 5 min before AA, dose-dependently diminished aggregation, ATP-release, and the synthesis of TXA2 and PGE2 with IC50 values of 78, 115, 71, and 86 mumol/l, respectively. The similarity of the IC50 values suggest an inhibition of COX by (+)-kavain as primary target, thus suppressing the generation of TXA2 which induces aggregation of platelets and exocytosis of ATP by its binding on TXA2-receptors.

Gutser UT, Friese J, Heubach JF, Matthiesen T, Selve N, Wilffert B, Gleitz J. Mode of antinociceptive and toxic action of alkaloids of Aconitum spec.. Naunyn Schmiedebergs Arch Pharmacol 1998;357(1):39-48.
Extracts of the plant Aconitum spec. are used in traditional Chinese medicine predominantly as anti-inflammatory and analgesic agents, the latter allegedly equally potent as morphine but without any habit-forming potential. As the only pharmacologically active compounds, the C19 diterpenoid alkaloid aconitine, and some of its derivatives, have been proven to be antinociceptive in different analgesic assays, but the mode of action is unknown. To elucidate the mode of action, ten aconitine-like derivatives were investigated with respect to their affinity for voltage-dependent Na+ channels, the action on synaptosomal Na+ and Ca2+ homoeostasis and their antinociceptive, arrhythmogenic and acute toxic properties. Since aconitine is known to bind to site II of Na+ channels, we determined the affinity of the aconitine-like derivatives in vitro to synaptosomal membranes by the [3H]-batrachotoxinin-binding assay and their properties on intrasynaptosomal concentrations of free Na+ and Ca2+ ([Na+]i and [Ca2+]i), both the latter determined fluorometrically with SBFI and Fura-2 respectively. Furthermore, the alkaloids' arrhythmogenic potential was investigated in guinea-pig isolated atria and the antinociceptive action on formalin-induced hyperalgesia and the acute toxic action estimated in mice. The results show that the alkaloids could be divided into at least three groups. The first is characterized by a high affinity to the site II of Na+ channels (Ki about 1.2 microM), the ability to enhance [Na+]i and [Ca2+]i (EC50 about 3 microM), a strong arrhythmogenic action that starts at about 30 nM, an antinociceptive effect (ED50 about 0.06 mg/kg) and high acute toxicity (LD50 values about 0.15 mg/kg). To this group belong aconitine, 3-acetylaconitine and hypaconitine. The second group, with lappaconitine as the only member, has an affinity to Na+ channels an order of magnitude lower (Ki = 11.5 microM), less acute toxicity (LD50 about 5 mg/kg), and a two orders of magnitude lower antinociceptive action (ED50 about 2.8 mg/kg) and lower cardiotoxicity (bradycardia observed at 3 microM). Additionally, lappaconitine suppresses the increase in [Ca2+]i of aconitine-stimulated synaptosomes and increases the excitation threshold of left atria, indicating an inhibition of Na+ channels. The other derivatives, i.e. delcorine, desoxydelcorine, karakoline, lappaconidine, lappaconine and lycoctonine, belong to the third group, which has hardly any effects. They have a low affinity to Na+ channels with Ki values in the millimolar range, show no effect on synaptosomal [Na+]i and [Ca2+]i, no arrhythmogenic potential up to 100 microM, no antinociceptive activity and low toxicity with LD50 values greater than 50 mg/kg. For the investigated alkaloids we suggest two different antinociceptive-like modes of action. Aconitine, hypaconitine and 3-acetylaconitine may induce a block of neuronal conduction by a permanent cell depolarisation, whereas lappaconitine might act like local anaesthetics. However, because of the low LD50/ED30 quotients of 2-6, the antinociceptive-like action of the Aconitum alkaloids seems to reflect severe intoxication rather than a specific antinociceptive action. The structure/activity relationship shows that alkaloids that activate or block Na+ channels have a benzoyl ester side chain in the C-14 or C-4 positions respectively, whereas the other compounds lack this group.

Hamasaki Y, Kobayashi I, Hayasaki R, Zaitu M, Muro E, Yamamoto S, Ichimaru T, Miyazaki S. The Chinese herbal medicine, shinpi-to, inhibits IgE-mediated leukotriene synthesis in rat basophilic leukemia-2H3 cells. J Ethnopharmacol 1997;56(2):123-31.
We examined the action of Shinpi-To (Formula divinita; TJ-85), a granular extract of seven Chinese medicinal herbs that is used in treating childhood asthma, on the leukotriene synthesis in rat basophilic leukemia-2H3 cells (RBL-2H3 cells). IgE-loaded cells were stimulated with anti-IgE serum in the presence or absence of Shinpi-To. Released LTC4 and LTB4 were measured by radioimmunoassay (RIA). Shinpi-To significantly inhibited IgE-mediated synthesis of leukotriene (LT)C4 and LTB4. To identify the inhibitory sites, we investigated the action of this extract on four synthetic enzymes, phospholipase A2 (PLA2), 5-lipoxygenase (5-LO). LTC4 synthase, and LTA4 hydrolase. Shinpi-To inhibited the A23187-stimulated release of [3H]arachidonic acid (AA) from the cell membrane, reflecting an effect on PLA2 activity. It also suppressed production of LTC4 and LTB4 when cell lysates were incubated with AA as substrate. It did not inhibit the production of LTC4 and LTB4 when LTA4-free acid was used as the substrate. Shinpi-To did not inhibit the IgE-mediated increase of intracellular Ca2+ ([Ca2+]i) concentration. Results indicate that Shinpi-To inhibits LT synthesis by inhibiting PLA2 and 5-LO activities without affecting the mobilization of [Ca2+]i.

Hong YS. Effect of diallyl sulfide on tetrachlorodibenzo-P-dioxin-induced cytochrome P-450 1A1 gene in mouse lung. Biochem Arch 1997;13(3):179-87.
BIOSIS COPYRIGHT: BIOL ABS. Cytochrome P-450 (CYP) 1A1 plays a key role in the metabolic activation of procarcinogen, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The present study was conducted to investigate inhibitory effect of diallyl sulfide and garlic extract on CYP1A1 induced by TCDD in mouse lung. CYP1A1 was induced by a single oral gavage of TCDD (100 ng/kg) to mouse and the induction was confirmed by the increase of its enzyme activity and of immunoprecipitable protein as well as that of mRNA for CYP1A1. When dially sulfide (200 mg/kg) or garlic extract (50 mg/kg) were given 4 days prior to TCDD administration, CYP1A1 activity measured by benzo(a)pyrene hydroxylase or 7-ethoxyresorufin-O-deethylase and the expression detected by Northern blot analysis using CYP1A1 cDNA decreased significantly in the lung compared to the TCDD-induced activities. On the other hand, those activities in the liver decreased moderately, indicating tissue specificity of the CYP gene expression. These results together with poor correlation of CYP1A2 activity under the same experimental condition indicate that the reduction of CYP1A1 gene expression by diallyl sulfide or garlic extract is selective in mouse lung induced by TCDD.

Hood B. Paclitaxel (Taxol): newly identified source of alcohol intoxication. Miss Pharm 1998;24(4):13.
IPA COPYRIGHT: ASHP The case of a 57-yr-old woman who developed symptoms of acute ethyl alcohol (ethanol) intoxication, with a blood alcohol concentration of 0.098%, during treatment with 200-348 mg/sq m paclitaxel (Taxol) per cycle is described. Concomitant therapy included diphenhydramine, belladonna alkaloids, phenobarbital, ergotamine tartrate, terfenadine, metoclopramide, morphine, amitriptyline, and hydrocodone.

Huber WW, Mcdaniel LP, Kaderlik KR, Teitel CH, Lang NP, Kadlubar FF. Chemoprotection against the formation of colon DNA adducts from the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the rat [see comments]. Mutat Res 1997;376(1-2):115-22.
The mutagenic heterocyclic aromatic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), is a pyrolysis product in cooked foods that has been shown to be a rat colon carcinogen and has been implicated in the etiology of human colon cancer. In order to identify chemoprotection strategies that could be carried out in humans, a pilot study was conducted in which PhIP-DNA-adduct levels were quantified in the colons of male F344 rats that had been subjected to 16 different putative chemoprotection regimens, followed by a gavage of PhIP (50 mg/kg) and sacrifice 24 h later. The 16 treatments (Oltipraz, benzylisothiocyanate, diallyl sulfide, garlic powder, ethoxyquin, butylated hydroxyanisole, glutathione, indole-3-carbinol, alpha-angelicalactone, kahweol/cafestol palmitates, quercetin, green tea, black tea, tannic acid, amylase-resistant starch, and physical exercise) comprised sulfur-containing compounds, antioxidants, flavonoids, diterpenes, polyphenols, high dietary fiber, etc. The strongest inhibition of PhIP-DNA adduct formation in the colon was observed upon pretreatment with black tea, benzylisothiocyanate, and a mixture (1:1) of kahweol:cafestol palmitates, which resulted in 67, 66, and 54% decreases in colon PhIP-DNA adduct levels, as compared with controls. Preliminary studies on their mechanism of action indicated that only kahweol:cafestol caused a substantial induction of glutathione S-transferase isozymes (GSTs) that are thought to be important in the detoxification of PhIP. Notably, this induction occurred in the liver rather than in the colon.

Huong NT, Matsumoto K, Kasai R, Yamasaki K, Watanabe H. In vitro antioxidant activity of Vietnamese ginseng saponin and its components. Biol Pharm Bull 1998;21(9):978-81.
To elucidate the antioxidant action of Vietnamese ginseng saponin against free radial-mediated cellular damage, we examined the effect of Vietnamese ginseng saponin on lipid peroxidation in the mouse brain, liver, and liver microsomes by using two in vitro free radical generating systems (iron ferrous+ascorbic acid and iron ferrous+hydrogen peroxide). Free radical-mediated lipid peroxidation was determined by measuring the endogenous and stimulated accumulation of thiobarbituric acid reactive substance (TBA-RS). Vietnamese ginseng saponin (0.05-0.5 mg/ml), as well as vitamin E, significantly inhibited the formation of TBA-RS in tissue homogenates. Panax ginseng saponin, at the same concentration range as Vietnamese ginseng saponin, also had inhibitory action on free radical-mediated lipid peroxidation. However, majonoside-R2, ginsenoside-Rg1 and ginsenoside-Rb1, the main saponin components of Vietnamese ginseng saponin fraction, had no effect on lipid peroxidation. These results suggest that Vietnamese ginseng exerts a protective action against free radical-induced tissue injury and that this effect is attributable to minor components rather than the main saponin components tested.

Ikeda Y, Iijima OT, Iizuka A, Ishige A, Amagaya S, Komatsu Y, Okada M, Abe C, Fujihira E. Anti-inflammatory effects of mao-bushi-saishin-to in mice and rats. Am J Chin Med 1998;26(2):171-9.
Effects of Mao-Bushi-Saishin-to (MBS) on anti-inflammatory activities were examined in mice and rats. MBS significantly inhibited the increase in vascular permeability induced by acetic acid, the ear edema induced by arachidonic acid and phorbol ester, and the cutaneous extravasation induced by bradykinin and histamine. MBS, however, was not effective against the serotonin-induced cutaneous permeability increase in mice. MBS significantly inhibited carrageenin-induced hind foot edema and cotton pellet-induced granulation tissue growth in rats. These results show that MBS may exert anti-inflammatory effects through the underlying mechanism(s) of preventing mediator release from mast cells and macrophages.

Imoto K, Takemura H, Kwan CY, Sakano S, Kaneko M, Ohshika H. Inhibitory effects of tetrandrine and hernandezine on Ca2+ mobilization in rat glioma C6 cells. Res Commun Mol Pathol Pharmacol 1997;95(2):129-46.
The effects of tetrandrine (TET), a Ca2+ antagonist of Chinese herbal origin, and hernandezine (HER), a structural analogue of TET, on Ca2+ mobilization were studied in rat glioma C6 cells. TET and HER alone did not affect the resting cytoplasmic Ca2+ concentration ([Ca2+]i). TET and HER inhibited the peak and sustained elevation of [Ca2+]i induced by bombesin and thapsigargin (TG), a microsomal Ca2+ ATPase inhibitor, in a dose-dependent manner. The doses of TET or HER needed to abolish the sustained and peak increase in [Ca2+]i induced by bombesin and TG were 30 microM and 300 microM, respectively. TET and HER did not increase inositol 1,4,5-trisphosphate (IP3) accumulation by themselves but inhibited IP3 accumulation elevated by bombesin. In permeabilized C6 cells, the addition of IP3 and TG released Ca2+ from intracellular stores. Pretreatment with TET or HER abolished Ca2+ release from intracellular stores induced by bombesin and TG. In the absence of extracellular Ca2+, the addition of 3 mM Ca2+ to extracellular medium slightly increased [Ca2+]i, which indicated Ca2+ entry due to leakage of Ca2+ at the plasma membrane but not Ca2+ influx through Ca2+ channels. TET and HER did not affect this leakage entry of Ca2+. The present results suggest that TET and HER inhibit Ca2+ release from intracellular stores as well as Ca2+ entry from extracellular medium evoked by bombesin and TG. In addition, TET and HER inhibit IP3 accumulation induced by bombesin in rat glioma C6 cells.

Ip C, Lisk DJ. Modulation of phase I and phase II xenobiotic-metabolizing enzymes by selenium-enriched garlic in rats. Nutr Cancer 1997;28(2):184-8.
Previous research showed that treatment with selenium-enriched garlic (Se-garlic) was able to inhibit the initiation phase of mammary carcinogenesis in the dimethyl-benz[a]anthracene (DMBA) model in rats. The present study was designed to investigate the following parameters: 1) DMBA-DNA adduct formation in liver and mammary gland, 2) urinary excretion of DMBA metabolites, 3) phase I and phase II xenobiotic-metabolizing enzymes, and 4) tissue selenium levels as a function of Se-garlic supplementation. Prior feeding with an Se-garlic-containing diet (at 3 ppm Se) for two weeks resulted in a consistent reduction of all DMBA adducts in liver and mammary gland. This was accompanied by a 40% increase in urinary excretion of DMBA metabolites over a two-day period. Several liver P-450 enzymes were examined in rats fed a diet supplemented with 1, 2, or 3 ppm Se. Compared with controls receiving 0.1 ppm Se, no significant alteration in activity was detected with respect to P-450 1A1 (responsible for DMBA activation), 1A2, 2B1, 2E1, and 3A4. In contrast, glutathione S-transferase and uridine 5'-diphosphate-glucuronyltransferase activities were elevated to a maximum of 2- to 2.5-fold in liver and kidney. As expected, there was a dose-dependent elevation of selenium concentrations in liver, kidney, mammary gland, and plasma as a function of the level of Se-garlic supplementation. Our data seem to suggest that an increased detoxification of carcinogen via the phase II conjugating enzymes might represent a mechanism of tumor suppression by Se-garlic.

Ip SP, Ma CY, Che CT, Ko KM. Methylenedioxy group as determinant of schisandrin in enhancing hepatic mitochondrial glutathione in carbon tetrachloride-intoxicated mice. Biochem Pharmacol 1997;54(2):317-9.
As a preliminary approach to exploring whether the methylenedioxy group of the dibenzocyclooctadiene skeleton of schisandrins plays an important role in hepatic mitochondrial-reduced glutathione (GSH) stimulatory activity, we examined the effects of three schisandrins, namely schisandrin A (Sch A), schisandrin B (Sch B), and schisandrin C (Sch C), on carbon tetrachloride (CCl4) hepatotoxicity and hepatic mitochondrial GSH status in mice. Pretreating mice with Sch A at a daily oral dose of 1 mmol/kg for 3 days did not protect against CCl4 hepatotoxicity, whereas pretreatment with Sch B or Sch C at the same dosage regimen produced almost complete protection. The hepatoprotection afforded by Sch B or Sch C pretreatment was associated with significant increases in the hepatic mitochondrial GSH level and glutathione reductase (EC 1.6.4.2) activity. Our results indicate that the methylenedioxy group of the dibenzocyclooctadiene skeleton of schisandrin is an important structural determinant in the stimulation of hepatic mitochondrial GSH, particularly under conditions of CCl4 intoxication.

Iqbal M, Athar M. Attenuation of iron-nitrilotriacetate (Fe-NTA)-mediated renal oxidative stress, toxicity and hyperproliferative response by the prophylactic treatment of rats with garlic oil. Food Chem Toxicol 1998;36(6):485-95.
Iron nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. In this communication we show that Fe-NTA-mediated nephrotoxicity is diminished by 1 wk of oral daily pretreatment of male albino Wistar rats with garlic oil given by gavage at 50 or 100 mg/kg body weight/ml corn oil. Intraperitoneal Fe-NTA treatment at a dose level of 9 mg Fe/kg body weight/10 ml enhances renal microsomal lipid peroxidation and hydrogen peroxide generation which are accompanied by a decrease in the activities of renal antioxidant enzymes (e.g. catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase), and a depletion in the level of renal glutathione. Parallel to these changes, a sharp increase in blood urea nitrogen and serum creatinine has been observed. In addition, Fe-NTA treatment also enhances renal ornithine decarboxylase (ODC) activity and increases [3H]thymidine incorporation into renal DNA. Prophylactic treatment of animals with garlic oil before the administration of Fe-NTA resulted in the diminution of Fe-NTA mediated injury. The enhancement of renal lipid peroxidation and hydrogen peroxide generation was decreased. In addition, there was recovery of glutathione depletion and inhibition of the activities of antioxidant enzymes. Similarly, in animals given the higher dose of garlic oil (100 mg/kg body weight) the enhanced blood urea nitrogen and serum creatinine levels, which are indicative of renal injury, showed a reduction of about 30% and 40%, respectively, in comparison with the group treated with Fe-NTA alone. Pretreatment with garlic oil also ameliorated the Fe-NTA-mediated induction of ODC activity and enhancement of [3H]thymidine incorporation into DNA in a dose-dependent manner. Our data suggest that garlic oil is a potent chemopreventive agent and may suppress Fe-NTA-induced nephrotoxicity.

Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm 1997;54(6):692-3.

Jeong HG. Suppression of constitutive and inducible cytochrome P450 gene expression by alpha-hederin in mice. Biochem Mol Biol Int 1998;46(5):1019-26. The effects of alpha-Hederin, a triterpenoid saponin which exists in some oriental herbs, on the expression of liver cytochrome P450s were examined in mice. The administration of alpha-Hederin to mice significantly decreased the hepatic content of P450 and the activities of microsomal ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, and aniline hydroxylase, representative activities of cytochrome-P4501A1, -P4501A2, and -P4502E1, respectively, in a dose- and time-dependent manner. However, pentoxyresorufin O-dealkylase, a representative activity of cytochrome P4502B1/2, was decreased to a lesser extent. alpha-Hederin also decreased inducible monooxygenase activities in the same manner. Suppressions of P450 isozyme expression occurred in alpha-Hederin treated hepatic microsomes, as determined by immunoblot analysis in a manner consistent with that of the enzyme activity levels. Levels of mRNA of P4501A1/2 and P4502B1/2 were also decreased by alpha-Hederin as shown by Northern blot analysis. In contrast, the level of P4502E1 mRNA in the liver of alpha-Hederin treated mice was unchanged. These results suggest that alpha-Hederin may act as a more specific suppressor for P4501A and P4502E1 than P4502B and that the suppression involves decreases in mRNA levels except in the case of P4502E1.

Jin L, Baillie TA. Metabolism of the chemoprotective agent diallyl sulfide to glutathione conjugates in rats. Chem Res Toxicol 1997;10(3):318-27.
The chemoprotective effects of diallyl sulfide (DAS), a flavor component of garlic, have been attributed to its inhibitory effects on CYP2E1-mediated bioactivation of certain carcinogenic chemicals. In addition to being a competitive inhibitor of CYP2E1 in vitro, DAS is known to cause irreversible inhibition of CYP2E1 in rats in vivo. The latter property is believed to be mediated by the DAS metabolite diallyl sulfone (DASO2), which is thought to be a mechanism-based inhibitor of CYP2E1, although the underlying mechanism remains unknown. In order to investigate the nature of the reactive intermediate(s) responsible for the inactivation of CYP2E1 by DAS and its immediate metabolites, the present studies were carried out to detect and identify potential glutathione (GSH) conjugates of DAS and its metabolites diallyl sulfoxide (DASO) and DASO2. By means of ionspray LC-MS/MS, ten GSH conjugates were identified in bile collected from rats dosed with DAS, namely: S-[3-(S'-allyl-S'-dioxomercapto)-2-hydroxypropyl]glutathione (M1, M2; diastereomers), S-[3-(S'-allyl-S'-dioxomercapto)-2-hydroxypropyl]-glutathione (M5), S-[2-(S'-allyl-S'-dioxomercapto)-1-(hydroxymethyl)ethyl]glutathio- n e (M3, M4; diastereomers), S-[3-(S'-allylmercapto)-2-hydroxypropyl]glutathione (M6), S-(3-hydroxypropyl)-glutathione (M7), S-(2-carboxyethyl)glutathione (M8), allyl glutathionyl disulfide (M9), and S-allylglutathione (M10). With the exception of M6, all of the above GSH conjugates were detected in the bile of rats treated with DASO, while only M3, M4, M5, M7, M8, and M10 were found in the bile of rats treated with DASO2. Experiments conducted in vitro showed that GSH reacted spontaneously with DASO to form conjugates M9 and M10, and with DASO2 to form M10. In the presence of NADPH and GSH, incubation of DAS with cDNA-expressed rat CYP2E1 resulted in the formation of metabolites M6, M9, and M10, while incubation with DASO led to the formation of M3, M4, M5, M9, and M10. When DASO2 acted as substrate, CYP2E1 generated only conjugates M3, M4, M5, and M10. These results indicate that while DAS and DASO undergo extensive oxidation in vivo at the sulfur atom, the allylic carbon, and the terminal double bonds, CYP2E1 preferentially catalyzes oxidation of the sulfur atom to form the sulfoxide and the sulfone (DASO and DASO2). However, it appears that the end product of this sequence, namely, DASO2, undergoes further CYP2E1-mediated activation of the olefinic pi-bond, a reaction which transforms many terminal olefins to potent mechanism-based P450 inhibitors. We hypothesize, therefore, that it is this final metabolic event with DASO2 which leads to autocatalytic destruction of CYP2E1 and which is mainly responsible for the chemoprotective effects of DAS in vivo.

Jung JH, Ha JY, Min KR, Shibata F, Nakagawa H, Kang SS, Chang IM, Kim Y. Reynosin from Sassurea lappa as inhibitor on CINC-1 induction in LPS-stimulated NRK-52E cells [letter]. Planta Med 1998;64(5):454-5.
An inhibitor on CINC-1 (cytokine-induced neutrophil chemoattractant-1) induction in LPS-stimulated rat kidney epithelioid NRK-52E cells was purified from the roots of Sassurea lappa Clarke, a herbal medicine used in Korean traditional prescriptions for gastric intestinal diseases by a variety of column chromatographic procedures. The inhibitor was identified as reynosin, a sesquiterpene lactone isolated and characterized previously from Ambrosia confertiflora DC., and Magnolia grandiflora L. Reynosin exhibited a dose-dependent inhibition on CINC-1 induction in LPS-stimulated NRK-52E cells, where 50% of inhibitory effect was shown at the concentration of about 1 microM.

Kaehler ST, Sinner C, Chatterjee SS, Philippu A. Hyperforin enhances the extracellular concentrations of catecholamines, serotonin and glutamate in the rat locus coeruleus. Neurosci Lett 1999;262(3):199-202.
Hyperforin is the main antidepressant component of hypericum perforatum (St. John's Wort). Using the push-pull superfusion technique we tested whether hyperforin influences extracellular concentrations of neurotransmitters in the rat locus coeruleus. Hyperforin (10 mg/kg, i.p.) not only enhanced the extracellular levels of the monoamines dopamine, noradrenaline and serotonin, but also that of the excitatory amino acid glutamate. The levels of the main serotonin metabolite 5-hydroxyindolacetic acid, as well as those of the amino acids GABA, taurine, aspartate, serine and arginine, were not influenced. Together with in vitro studies, our findings suggest that the antidepressant property of hyperforin is due to enhanced concentrations of monoamines and glutamate in the synaptic cleft, probably as a consequence of uptake inhibition.

Kanai S, Okano H. Mechanism of the protective effects of sumac gall extract and gallic acid on the progression of CCl4-induced acute liver injury in rats. Am J Chin Med 1998;26(3-4):333-41.
To examine the mechanism of the preventive effect of tannins on the progression of carbon tetrachloride (CCl4)-induced acute liver injury in rats, sumac gall (SG) extract and gallic acid (GA) were used as substitutes for crude tannins, because SG is a kind of Chinese traditional medicinal herb containing large amounts of various tannins, and GA is one of the major constituents of SG. The protective effect of oral (p.o.) and intraperitoneal (i.p.) administration of each substance on progression of CCl4-induced hepatitis was investigated in rats. Speculating that the superoxide dismutase (SOD)-like activities (O2 radical-scavenging activities) and/or protective effects of these substances on cell membranes might play a key role in the mechanism opposing the progression of CCl4-induced hepatitis, the O2 radical-scavenging activities in liver cells and serum in rats were monitored. Both substances significantly prevented the progression of acute liver injury with both p.o. and i.p. administration. These findings suggest that the mechanism for this prevention might be due mainly to the protective effect of these substances on cell membranes rather than O2 radical-scavenging activities.

Kar A, Choudhary BK, Bandyopadhyay NG. Preliminary studies on the inorganic constituents of some indigenous hypoglycaemic herbs on oral glucose tolerance test. J Ethnopharmacol 1999;64(2):179-84.
Medicinal herbs used in indigenous medicines in crude forms for the management of diabetes mellitus, contain both the organic and inorganic constituents. It is known that certain inorganic mineral elements (potassium, zinc, calcium, traces of chromium, etc.) play an important role in the maintenance of normal glucose-tolerance and in the release of insulin from beta cells of islets of Langerhans. In the present study, 30 hypoglycaemic herbs were selected from indigenous folk medicines, Ayurvedic, Unani and Siddha systems of medicines. Special emphasis was given to their inorganic parts by carefully preparing ash (which contains mainly mineral elements) of the specific parts of the herbal samples under study. Next, the single dose effect on the oral glucose tolerance test (GTT) was studied using previously fasted albino rats. Similar effects were also compared with their organic parts of the concerned herbal samples in the form of 95% ethanolic extracts. In certain inorganic samples, more pronounced action (as glucose tolerance factor) were noticed than their corresponding organic parts.

Khojasteh-Bakht SC, Chen W, Koenigs LL, Peter RM, Nelson SD. Metabolism of (R)-(+)-pulegone and (R)-(+)-menthofuran by human liver cytochrome P-450s: evidence for formation of a furan epoxide. Drug Metab Dispos 1999;27(5):574-80.
(R)-(+)-Pulegone, a monoterpene constituent of pennyroyal oil, is a hepatotoxin that has been used in folklore medicine as an abortifacient despite its potential lethal effects. Pulegone is metabolized by human liver cytochrome P-450s to menthofuran, a proximate hepatotoxic metabolite of pulegone. Expressed human liver cytochrome (CYP) P-450s (1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4) were tested for their ability to catalyze the oxidations of pulegone and menthofuran. Expressed CYP2E1, CYP1A2, and CYP2C19 oxidized pulegone to menthofuran, with respective Km and Vmax values of 29 microM and 8.4 nmol/min/nmol P-450 for CYP2E1, 94 microM and 2.4 nmol/min/nmol P-450 for CYP1A2, and 31 microM and 1.5 nmol/min/nmol P-450 for CYP2C19. The human liver P-450s involved in the metabolism of menthofuran are the same as pulegone except for the addition of CYP2A6. These P-450s were found to oxidize menthofuran to a newly identified metabolite, 2-hydroxymenthofuran, which is an intermediate in the formation of the known metabolites mintlactone and isomintlactone. Based on studies with 18O2 and H218O, 2-hydroxymenthofuran arises predominantly from a dihydrodiol formed from a furan epoxide. CYP2E1, CYP1A2, and CYP2C19 oxidized menthofuran with respective Km and Vmax values of 33 microM and 0.43 nmol/min/nmol P-450 for CYP2E1, 57 microM and 0.29 nmol/min/nmol P-450 for CYP1A2, and 62 microM and 0.26 nmol/min/nmol P-450 for CYP2C19.

Kim HS, Hong YT, Jang CG. Effects of the ginsenosides Rg1 and Rb1 on morphine-induced hyperactivity and reinforcement in mice. J Pharm Pharmacol 1998;50(5):555-60.
Recent studies have demonstrated that ginseng saponin inhibits the hyperactivity and conditioned place-preference response induced by psychostimulants and opiates. This seems to occur by direct or indirect modulation of dopaminergic activity. However, it is not known which components of ginseng saponin are active. These experiments were conducted to determine the effects of the ginsenosides Rb1 and Rg1, major components of the protopanaxadiol and protopanaxatriol fractions of ginseng saponin, on morphine-induced hyperactivity and conditioned place-preference. Morphine-induced hyperactivity, but not apomorphine-induced climbing behaviour, was inhibited by both Rb1 and Rg1. These findings confirm the hypothesis that ginsenosides modulate catecholaminergic activity preferentially at pre-synaptic sites. Morphine-induced conditioned place-preference was inhibited by Rg1, but not by Rb1. It has previously been shown that at low doses Rb1 and Rg1 are equally effective at inhibition of catecholamine secretion at the pre-synaptic site, but that at high doses Rg1 is a more effective inhibitor. This observation might explain our finding that morphine-induced conditioned place-preference was inhibited by Rg1 only. Our findings suggest that Rg1, a component of ginseng saponin with appropriate activity, might be a useful agent for prevention and treatment of the adverse effects of morphine.

Kim HS, Hong YT, Oh KW, Seong YH, Rheu HM, Cho DH, Oh S, Park WK, Jang CG. Inhibition by ginsenosides Rb1 and Rg1 of methamphetamine-induced hyperactivity, conditioned place preference and postsynaptic dopamine receptor supersensitivity in mice. Gen Pharmacol 1998;30(5):783-9.
The ginsenosides Rb1 and Rg1, the major components of ginseng saponin, inhibited not only methamphetamine-induced hyperactivity but also conditioned place preference (CPP) in mice following a single or repeated administration. Dopamine (DA) receptor supersensitivity, which developed in methamphetamine-induced CPP mice, was also inhibited by both Rb1 and Rg1. Therefore, the present results suggest that Rb1 and Rg1 may be the active components of ginseng saponin in the modulation of methamphetamine-induced dopaminergic behaviors such as hyperactivity and CPP, supporting our previous conclusion that ginseng saponin might modulate methamphetamine-induced dysfunction at both the pre- and postsynaptic DA receptors.

Kim YC, Kim SR, Markelonis GJ, Oh TH. Ginsenosides Rb1 and Rg3 protect cultured rat cortical cells from glutamate-induced neurodegeneration [published erratum appears in J Neurosci Res 1998 Oct 1;54(1):123]. J Neurosci Res 1998;53(4):426-32.
Certain natural products and Asian herbal remedies have been used in Asia to attenuate neurodegenerative diseases, including senile dementia. We have examined derivatives of several natural products for potential neuroprotective activity in an in vitro test system. In the present study, we assayed a number of compounds that were isolated from Panax ginseng C.A. Meyer (Araliaceae) for an ability to protect rat cortical cell cultures from the deleterious effects of the neurotoxicant, glutamate. We found that ginsenosides Rb1 and Rg3 significantly attenuated glutamate-induced neurotoxicity. Brief exposure of cultures to excess glutamate caused extensive neuronal death. Glutamate-induced neuronal cell damage was reduced significantly by pretreatment with Rb1 and Rg3. Ginsenosides Rb1 and Rg3 inhibited the overproduction of nitric oxide, which routinely follows glutamate neurotoxicity, and preserved the level of superoxide dismutase in glutamate-treated cells. Furthermore, in cultures treated with glutamate, these ginsenosides inhibited the formation of malondialdehyde, a compound that is produced during lipid peroxidation, and diminished the influx of calcium. These results show that ginsenosides Rb1 and Rg3 exerted significant neuroprotective effects on cultured cortical cells. Therefore, these compounds may be efficacious in protecting neurons from oxidative damage that is produced by exposure to excess glutamate.

Kim YS, Kim DS, Kim SI. Ginsenoside Rh2 and Rh3 induce differentiation of HL-60 cells into granulocytes: modulation of protein kinase C isoforms during differentiation by ginsenoside Rh2. Int J Biochem Cell Biol 1998;30(3):327-38.
Ginsenoside Rh1 or Rh2 differentiated B16 melanoma or F9 teratocarnoma to phenotypic normal melanocyte-like cells or parietal endoderm-like cells. Ginsenoside Rh3 and Rh4 were recently isolated from Panax ginseng, but their biochemical and pharmacological effects remain unidentified. The present study investigated whether the ginsenoside Rh group (G-Rh1, -Rh2, -Rh3 and -Rh4) having similar structures induce differentiation of HL-60 cells and whether protein kinase C (PKC) is involved in differentiation by ginsenoside. Differentiation was assessed by Wright-Giemsa stain and nitroblue tetrazolium reduction. G-Rh2 and G-Rh3 induced differentiation of HL-60 cells into morphologically and functionally granulocytes but G-Rh1 and G-Rh4 did not. G-Rh2 and G-Rh3 arrested the cell cycle at the G1/S phase, consistent with the ability to induce differentiation in a decreasing order of retinoic acid > G-Rh2 > G-Rh3. During differentiation by G-Rh2, Ca2+/phospholipid-dependent PKC activity was increased in both the cytosol and total cell extract and Ca2+/phospholipid-dependent phosphorylation of 38 and 200 kDa endogenous proteins increased, while phosphorylation of 60, 64, 66 and 97 kDa proteins was Ca2+/phospholipid-independent. When cytosolic PKC isoforms were analyzed by immunoblotting, no significant change was observed in the alpha level, however, the immunoreactive 60 kDa band of a similar mass to the PKC catalytic fragment appeared following treatment with G-Rh2. The beta isoform was gradually increased with prolonged treatment. The gamma isoform was not detected in the cytosol of untreated cells, whereas a small amount was detected 5 days after treatment. It is concluded that G-Rh2 and G-Rh3 can induce differentiation of HL-60 cells into granulocytes and modulation of PKC isoform levels may contribute to differentiation of HL-60 cells by G-Rh2.

Kim YW, Song DK, Kim WH, Lee KM, Cho MK, et al . Long term oral administration of ginseng extract decreases serum gamma globulin and IgG1 isotype in mice. J Ethnopharmacol 1997;58(1):55-8.
IPA COPYRIGHT: ASHP The effects of long term treatment with ginseng extract on the serum protein profile and immunoglobulin isotypes were studied in mice after an oral dose of 30 or 150 mg/kg/day ginseng extract for 52 days. Serum levels of gamma-globulin were decreased to 82% and 56% of control values during treatment with 30 and 150 mg/kg/day extract, respectively. Levels of total protein, albumin, alpha2- and beta-globulin fractions, and the ratio of albumin to globulin did not change significantly. However, the alpha1-globulin level increased by 24% during treatment with the extracts. Serum IgG1 was dose dependently decreased to 68% of control values at the dose of 150 mg/kg/day, without significant changes in other Ig isotypes.

Kleber E, Obry T, Hippeli S, Schneider W, Elstner EF. Biochemical activities of extracts from Hypericum perforatum L. 1st Communication: inhibition of dopamine-beta-hydroxylase. Arzneimittelforschung 1999;49(2):106-9.
Extracts from the herb "St. John's wort" (Hypericum perforatum L.) are used for the treatment of mental depression, nervousness, sleeplessness and for their wound healing, diuretic and antirheumatic properties. As one biochemical mechanism for depression lack of catecholamine neurotransmitters has been discussed. The results of this investigation show that alcoholic extracts from Hypericum perforatum L. on the basis of total hypericin content inhibit dopamine-beta-hydroxylase with an IC50 of 0.1 mu mol/l; pure commercial hypericin inhibits with an IC50 of 21 mu mol/l. Enzymes involved in the synthesis of dopamine from tyrosine, namely tyrosinase and tyrosine decarboxylase, are not influenced by hypericin at concentrations from 1 up to 10 mu mol/l.

Koike K, Zhang ZX, Sakamoto Y, Jikihara H, Masuhara K, Murakami K, Miyake A, Inoue M. The herbal medicine unkei-to stimulates cytokine-induced neutrophil chemoattractant production in the pituitary folliculo-stellate-like cell line (TtT/GF). Am J Reprod Immunol 1998;39(4):249-55.
PROBLEM: We previously reported that a cytokine-induced neutrophil chemoattractant (CINC) was produced in the pituitary gland and that it influenced anterior pituitary hormone release. In this study we investigated the effect of Unkei-to, a Japanese herbal medicine, on CINC production in the rat anterior pituitary gland and the pituitary folliculo-stellate-like cell line (TtT/GF). METHOD OF STUDY: Dispersed normal anterior pituitary cells and the folliculo-stellate-like cell line TtT/GF were used to test the effect of Unkei-to on CINC secretion and CINC mRNA accumulation. Concentrations of CINC in the conditioned media were measured by an enzyme-linked immunosorbent assay, and levels of CINC mRNA were analyzed by Northern blot analysis. RESULTS: Unkei-to (20 micrograms/ml) significantly increased the secretion of CINC by normal anterior pituitary cells within 12 hr of incubation. Unkei-to also stimulated CINC secretion from TtT/GF cells in a time- and dose-dependent manner. Unkei-to (20 micrograms/ml) increased CINC mRNA accumulation in TtT/GF cells within 3 hr of incubation and also caused a 13-fold increase in the secretion of CINC from TtT/GF cells compared with the vehicle group within 24 hr of incubation. Finally, we found that some of the Unkei-to's ingredients, Evodiae fructus and Pinelliae tuber, markedly stimulated CINC secretion from TtT/GF cells. CONCLUSIONS: Our results will help to elucidate the mechanism behind the clinical effect of Unkei-to on the anterior pituitary gland. They also suggested the presence of special substances, which stimulate CINC secretion, within Unkei-to's ingredients such as E. fructus and P. tuber.

Kyo R, Nakahata N, Sakakibara I, Kubo M, Ohizumi Y. Baicalin and baicalein, constituents of an important medicinal plant, inhibit intracellular Ca2+ elevation by reducing phospholipase C activity in C6 rat glioma cells. J Pharm Pharmacol 1998;50(10):1179-82.
Glial cells have a role in maintaining the function of neural cells. This study was undertaken to clarify the effects of baicalin and baicalein, flavonoids isolated from an important medicinal plant Scutellariae Radix (the root of Scutellaria baicalensis Georgi), on glial cell function using C6 rat glioma cells. Baicalin and baicalein caused concentration-dependent inhibition of a histamine-induced increase in intracellular Ca2+ concentrations ([Ca2+]i). The potency of baicalein was significantly greater than that of baicalin. The noradrenaline- and carbachol-induced increase in [Ca2+]i was also inhibited by baicalein and both drugs inhibited histamine-induced accumulation of total [3H]inositol phosphates, consistent with their inhibition of the increase in [Ca2+]i. These results suggest that baicalin and baicalein inhibit [Ca2+]i elevation by reducing phospholipase C activity. The inhibitory effects of baicalin and baicalein on [Ca2+]i elevation might be important in the interpretation of their pharmacological action on glial cells, such as inhibition of Ca2(+)-required enzyme phospholipase A2.

Lee BH, Lee SJ, Hui JH, Lee S, Sung JH, Huh JD, Moon CK. In vitro antigenotoxic activity of novel ginseng saponin metabolites formed by intestinal bacteria. Planta Med 1998;64(6):500-3.
Ginseng saponin metabolites produced by human intestinal bacteria were evaluated for antigenotoxic properties by testing their effects on benzo[a]pyrene (B[a]P)-induced mutagenicity and clastogenicity. They include 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH-901), 20-O-(alpha-D-arabinopyranosyl(1-->6)-beta-D-glucopyranosyl]- 20(S)-protopanaxadiol (IH-902) and 20-O-[alpha-D-arabinofuranosyl(1-->6)-beta-D-glucopyranosyl]-20(S- )- protopanaxadiol (IH-903). IH-901, IH-902 and IH-903 inhibited the mutagenicity of B[a]P in a dose-dependent manner. In the chromosome aberration assay, IH-901 and IH-903 reduced the frequency of chromosome aberration induced by B[a]P. These results suggest that the ginseng saponin metabolites tested in the present study have potential as chemopreventive agents.

Lee MJ, Lee OH, Yoon SH, Lee SK, Kim KW, et al . In vitro angiogenic activity of Aloe vera gel on calf pulmonary artery endothelial (CPAE) cells. Arch Pharmacal Res 1998;21(3):260-5.

Leung YM, Ou YJ, Kwan CY, Loh TT. Specific interaction between tetrandrine and Quillaja saponins in promoting permeabilization of plasma membrane in human leukemic HL-60 cells. Biochim Biophys Acta 1997;1325(2):318-28.
Spontaneous Ni2+ entry (leak), measured as fluorescence quench in fura-2-loaded HL-60 cells at the excitation wavelength of 360 nm, was strongly inhibited by tetrandrine (TET, 100 microM), a Ca2+ antagonist of Chinese herbal origin. Exposure of the cells for 5 min to saponins from Quillaja saponaria (QS, 30 microg/ml), surfactants well known to permeabilize the plasma membrane by complexing with cholesterol, promoted Ni2+ entry without causing fura-2 leak-out. Unexpectedly, TET caused an immediate (within 2.5 min) augmentation of QS-promoted Ni2+ entry; and a 5-min treatment with both TET and QS resulted not only in an enhanced Ni2+ entry, but also a fura-2 leak-out. Ginseng saponins (100 microg/ml) alone or together with TET did not cause such a permeabilization. Permeabilization induced by 1-3 microM digitonin, another cholesterol-complexing glycoside, could not be enhanced by TET. TET did not affect permeabilization induced by Triton X-100 (0.01%), a detergent which non-specifically disrupts the hydrophobic interaction at the plasma membrane. TET also did not enhance Ni2+ entry triggered by ionomycin (0.35 microM) or SK&F 96365 (20 microM). Further, it did not augment Ni2+ entry when the plasma membrane fluidity was modulated by changes of temperature (27-47 degrees C) or treatment with 5% ethanol. This QS-promoted Ni2+ entry could not be amplified by other lipophilic Ca2+ antagonists, such as diltiazem (100 microM) and verapamil (100 microM). The results hence indicate that TET enhanced Ni2+ entry (or permeabilization) elicited by QS treatment, but not other perturbations of the plasma membrane. We suggest that pore formation at the plasma membrane, a consequence of QS-cholesterol interaction, can be specifically enhanced by TET. Also, a comparative study of the effects of TET and its very close analogues, hernandezine and berbamine, reveals that the methoxyl group at the R2 position of TET appears to be crucial in enhancing QS-promoted Ni2+ entry.

Li JQ, Zhang XG, Zhang JT. [Study on the anti-apoptotic mechanism of ginsenoside Rg1 in cultured cortical neurons]. Yao Hsueh Hsueh Pao 1997 Jun;32:406-10. (Chi)
IPA COPYRIGHT: ASHP A study on the anti-apoptotic mechanism of ginsenoside Rg1, an active principle isolated from Panax ginseng CA Meyer, in cultured cortical neurons was performed with different concentrations of the drug. On day 14, the culture was changed to serum-free medium. On day 16, neurons were harvested and assayed microscopically; membrane fluidity was measured using fluorescence spectrophotometer in 5 groups of cultured cortical neurons. Results showed that serum withdrawal from the medium induced apoptosis in primary cultured cortical neurons. Ginsenoside Rg1 (1.10 mumol/l) was shown to inhibit apoptosis and protect neurons against injury. Findings indicated that a substantial alteration of membrane fluidity occurred with neuronal apoptosis. Changes in membrane fluidity provide an aspect of elucidating the mechanism of ginsenoside Rgl's anti-apoptosis function.

Li LL, Wang XW, Wang XF. [Antilipid peroxidation and antiradiation of glycosides of herba Cistanches(GCs)]. Zhongguo Zhongyao Zazhi 1997;22(6):364-7. (Chi)
IPA COPYRIGHT: ASHP The effects of the oral administration of glycosides isolated from herbs of Cistanche species on red blood cells and the contents of nucleic acids in the liver, kidneys, and spleen were studied in mice. Results suggested that the protective effects of Cistanche on nucleic acid and antiradiative actions may be related to its antilipid peroxidation.

Liao JF, Huang SY, Jan YM, Yu LL, Chen CF. Central inhibitory effects of water extract of Acori graminei rhizoma in mice. J Ethnopharmacol 1998;61(3):185-93.
The present study evaluated in mice the central inhibitory effects of a water extract of shichangpu (Acori graminei rhizoma (AGR), the dry rhizome of Acorus gramineus Soland. (Araceae)). AGR (0.5-5.0 g/kg) dose-dependently decreased the locomotor activity and increased the pentobarbital-induced sleeping time, but had no significant effect on the treadmill performance. AGR also dose-dependently inhibited the intensity of apomorphine-induced stereotypic behavior. At the highest dose (5.0 g/kg), AGR had a weak anticonvulsant effect on the pentylenetetrazol-induced seizures. Receptor binding assays showed that AGR competed with [3H]SCH-23390 and [3H]YM-09151-2 for specific binding to striatal dopamine D1 and D2 receptors with Ki values of 5.6 and 4.2 mg/ml, respectively. AGR also competed with [3H]muscimol for specific binding to the gamma-aminobutyric acid (GABA) binding site of cortex GABA(A) receptors with a Ki value of 0.31 mg/ml. It also increased the specific binding of [3H]flunitrazepam to the benzodiazepine binding site of the GABA(A) receptors, suggesting a GABA agonist-like action. These results suggested that the central inhibitory effects of AGR were probably effected through an action on the central dopamine receptors and GABA(A) receptors. The principle of AGR acting at these ligand binding sites was not alpha-asarone, one of the important principles of AGR, since that alpha-asarone (10(-6)-10(-4) M) had no significant interactions with these binding sites.

Liao MH, Wu CC, Yen MH. Beneficial effects of tetramethylpyrazine, an active constituent of Chinese herbs, on rats with endotoxemia. Proc Natl Sci Counc Repub China B 1998;22(1):46-54.
Tetramethylpyrazine, an inhibitor of phosphodiesterase, has been widely used for treatment of cardiovascular diseases in China. Here, we investigate the effects of tetramethylpyrazine on hypotension, vascular hyporeactivity to norepinephrine (NE), release of tumor necrosis factor-alpha (TNF alpha) and nitric oxide (NO) in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide, LPS). Male Wistar-Kyoto rats were anesthetized and instrumented for the measurement of mean arterial pressure (MAP) and heart rate (HR). Injection of LPS (10 mg/kg, i.v.) resulted in a fall in MAP and an increase of HR. In contrast, animals pretreated with tetramethylpyrazine (10 micrograms/kg, i.p. at 30 min prior to LPS) maintained a significantly higher MAP, but tachycardia was further enhanced at 60 min and 120 min when compared to rats given only LPS (LPS-rats). The pressor effect of NE (1 microgram/kg, i.v.) was also significantly reduced after treatment of rats with LPS. Similarly, the thoracic aorta obtained from rats after in vivo studies showed a significant reduction in the contractile responses elicited by NE (1 microM). Pretreatment of LPS-rats with tetramethylpyrazine partially, but significantly, prevented this LPS-induced hyporeactivity to NE in vivo and ex vivo. The injection of LPS resulted in a significant increase in the plasma TNF alpha level at 60 min, whereas the effect of LPS on the plasma nitrate (an indicator of NO formation) level increased in a time-dependent manner. This increment of both TNF alpha and nitrate levels induced by LPS was significantly reduced in LPS-rats pretreated with tetramethylpyrazine. The early hypotension caused by LPS was slightly, but significantly, prevented by pretreatment with tetramethylpyrazine, suggesting that tetramethylpyrazine affects the endothelial constitutive NOS (eNOS). This was examined by the effect of tetramethylpyrazine on acetylcholine (ACh, 1 microM)-induced relaxation in rats treated with tetramethylpyrazine for 4 h. However, tetramethylpyrazine had no significant effects on the ACh-induced relaxation, indicating that tetramethylpyrazine does not affect the activity of eNOS. Thus, tetramethylpyrazine attenuates the early hypotension and the delayed circulatory failure caused by endotoxin in the rat. These effects may be due to inhibition of the release of circulation factors and TNF alpha, which usually reveal synergism upon the induction of iNOS.

Lin HL, Liu TY, Lui WY, Chi CW. Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells. Cancer 1999;85(9):1937-42.
BACKGROUND: Berberine, one of the major constitutents of alkaloids of Coptis chinensis is frequently utilized in the treatment of inflammation and liver-related diseases. In Chinese herbal medicine, Coptis chinensis is used as a prophylactic drug to treat gastrointestinal disorders. In a previous study, the authors found that berberine reduced cell proliferation and alpha-fetoprotein expression in human hepatoma HepG2 cells. Multidrug resistance transporter (pgp-170) is known to be overexpressed in HepG2 cells. Whether berberine regulates the expression of pgp-170 in HepG2 and other hepatoma cell lines is unknown and worthy of investigation. METHODS: Human and murine hepatoma cells were treated with berberine (0.32, 3.2, 32, and 320 microM), tamoxifen (1 microM), or verapamil (10 microM) for 24 hours. Flow cytometry was used to measure retention of a fluorescence dye, rhodamine 123, and the level of immunoreactive pgp-170 in berberine-treated hepatoma cells. RESULTS: Berberine up-regulated the expression of pgp-170 in three human hepatoma cell lines. The function of pgp-170 was blocked by tamoxifen and verapamil, resulting in increased retention of rhodamine 123. Retention of rhodamine 123 was significantly reduced in berberine-treated hepatoma cells. CONCLUSIONS: Berberine modulates the expression and function of pgp-170 in hepatoma cells. These results suggest that treatment of tumor cells with berberine may result in reduced retention of chemotherapeutic agents.

Lin JK, Chen YC, Huang YT, Lin-Shiau SY. Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin. J Cell Biochem Suppl 1997;28-29:39-48.
Apigenin, a less-toxic and non-mutagenic flavonoid, suppressed 12-0-tetradecanoyl-phorbol-13-acetate-(TPA)-mediated tumor promotion of mouse skin. TPA had the ability to activate protein kinase C (PKC) and induced nuclear proto-oncogene expression. Our study indicates that apigenin inhibited PKC by competing with adenosine triphosphate (ATP). Apigenin also reduced the level of TPA-stimulated phosphorylation of cellular proteins and inhibited TPA-induced c-jun and c-fos expression. Curcumin, a dietary pigment phytopolyphenol, is also a potent inhibitor of tumor promotion induced by TPA in mouse skin. When mouse fibroblast cells were treated with TPA alone, PKC translocated from the cytosolic fraction to the particulate fraction. Treatment with 15 or 20 microM curcumin for 15 min inhibited TPA-induced PKC activity in the particulate fraction by 26-60%. Curcumin also inhibited PKC activity in vitro by competing with phosphatidylserine. Curcumin (10 microM) suppressed the expression of c-jun in TPA-treated cells. Fifteen flavonoids were examined for their effects on morphological changes in soft agar and cellular growth in v-H-ras transformed NIH3T3 cells. The results demonstrated that only apigenin, kaempferol, and genistein exhibited the reverting effect on the transformed morphology of these cells. Based on these findings, it is suggested that the suppression of PKC activity and nuclear oncogene expression might contribute to the molecular mechanisms of inhibition of TPA-induced tumor promotion by apigenin and curcumin.

Lis-Balchin M, Hart S. A preliminary study of the effect of essential oils on skeletal and smooth muscle in vitro. J Ethnopharmacol 1997;58(3):183-7.
The pharmacological activity of nine commercial essential oils was studied on the rat isolated phrenic nerve diaphragm preparation and compared with activity on field-stimulated guinea-pig ileum preparations. The essential oils at final bath concentrations of 2 x 10(-5) and 2 x 10(-4) g/ml produced four different effects on skeletal muscle, whilst only a contracture with or without a decrease in response to field stimulation in smooth muscle. The first type of effect on skeletal muscle involved a contracture and inhibition of the twitch response to nerve stimulation shown by a sample of clary sage, dill, fennel, frankincense and nutmeg; a second, shown by thyme produced a contracture without a change in the twitch response; a third, shown by lavender reduced the twitch response alone and the fourth, shown by camphor, increased the size of the twitch response. Angelica root oil at the highest concentration studied showed no response on skeletal muscle.

Liu W, Xiao K, Zhou J, He M, Sun H, Tang J. Study on the protective effects of compound blood-activating soup on bone marrow hematopoietic cells in acute radiation injured mice. J Tongji Med Univ 1997;17(4):225-8.
After irradiation with 8 Gy 60Co gamma-ray, mice were immediately given intraperitoneal injection of 200 mg 100% compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow hematopoietic cells in Chinese drug group was found to be higher than that in normal group, and it was also significantly higher than that in control group. The expression level of GADD153 gene which was not expressed in normal group was much lower in Chinese drug group than that in control group. On the 7th day after irradiation, the P53 and GADD153 gene expression levels of splenic mononuclear cells were consistent with those of bone marrow hematopoietic cells both in Chinese drug group and control group. On the 3rd and 7th day, the bone marrow hematopoietic tissue volume in Chinese drug group was higher than that in control group, with no difference found between the two groups. While on the 14th day, the difference became significant (P < 0.01). The results showed that commonly used blood-activating and stasis-eliminating drugs may strengthen the viability of hematopoietic cells and promote the rehabilitation of hematopoiesis by inducing wt-P53 expression to block the bone marrow hematopoietic cells in G1 phase, during which DNA could be repaired.

Liu YP, Liu J. Effect of alpha-hederin on hepatic detoxifying systems in mice. Chung Kuo Yao Li Hsueh Pao 1997;18(1):33-6.
AIM: To examine whether alpha-hederin (Hed) modulates hepatic detoxifying systems as a means of hepatoprotection. METHODS: Mice were injected Hed 10 and 30 mumol.kg-1 sc for 3 d, and liver cytosols were prepared 24 h after the last dose to study antioxidant enzymes and nonenzymatic defense components. RESULTS: Hed increased liver glutathione (GSH) content (20%), but had no effect on GSH peroxidase, GSH reductase, and GSH S-transferase. The activities of superoxide dismutase and quinone reductase were unaffected by Hed treatment. At the high dose of Hed, catalase activity was decreased by 20%. Hepatic content of metallothionein was dramatically increased (50-fold), along with elevations of hepatic Zn and Cu concentrations (25%-80%). Hed also increased ascorbic acid concentration (20%), but no effect on alpha-tocopherol in liver. CONCLUSION: Hed enhanced some nonenzymatic antioxidant components in liver, which play a partial role in Hed protection against hepatotoxicity produced by some chemicals.

Loew D. Is the biopharmaceutical quality of extracts adequate for clinical pharmacology? Int J Clin Pharmacol Ther 1997 Jul;35:302-6.
IPA COPYRIGHT: ASHP Guidelines for the scientific proof of equivalence and interchangeability of chemical/synthetic substances are described, including instances in which chemical and/or synthetic substances are considered equivalent, equivalence standards for phytopharmaceuticals, classification of the active ingredients of phytopharmaceuticals with drug examples, the definition of pharmaceutical equivalence, biopharmaceutical and therapeutical equivalence of phytopharmaceuticals, criteria for deciding on bioequivalence trials, and problems in demonstrating the bioequivalence of phytopharmaceuticals.

Madyastha KM, Gaikwad NW. Metabolic fate of S-(-)-pulegone in rat. Xenobiotica 1998;28(8):723-34.
1. S-(-)-pulegone was administered orally to rat (250 mg/kg) and the nature of the urinary metabolites was investigated. Eleven metabolites, namely S-(-)-menthofuran, piperitone, piperitenone, p-cresol, 5-hydroxypulegone, 4-methylcyclohexenone, 3-methylcyclohexanone, isopulegone, pulegol, 7-hydroxypiperitone and benzoic acid, have been isolated from rat urine. It is assumed that menthofuran, isopulegone and 4-methylcyclohexenone retain the stereochemistry of the parent compound, whereas in other metabolites the stereochemistry at the asymmetric centres is not known. 2. The relative amounts of various major metabolites present in the total urine extracts from the R-(+) and S-(-)-pulegone-treated rat were established by glc analyses. Urine samples of rats treated with R-(+)-pulegone contained higher levels of p-cresol and piperitenone than in similar experiment carried out with S-(-)-pulegone, whereas the levels of unmetabolized pulegone, piperitone and benzoic acid were considerably higher in the urine of rat treated with S-(-)-pulegone than in a corresponding experiment with R-(+)-pulegone. 3. Phenobarbital-induced rat liver microsomes converted S-(-)-pulegone to S-(-)-menthofuran (VII) and piperitenone (III) in the presence of NADPH and O2. The levels of VII and III were significantly higher in similar experiments carried out with R-(+)-pulegone. 4. Based on these studies, metabolic pathways for the biotransformation of S-(-)-pulegone in rat have been proposed and possible reasons for the observed difference in the toxicity mediated by these two enantiomers are discussed.

Madyastha KM, Gaikwad NW. Metabolism disposition of a monoterpene ketone, piperitenone, in rats: Evidence for the formation of a known toxin, p-cresol. Drug Metab Dispos 1999;27(1):74-80.
BIOSIS COPYRIGHT: BIOL ABS. It was shown earlier that the monoterpene ketone, piperitenone (I) is one of the major metabolites of R-(+)-pulegone, a potent hepatotoxin. In the present studies, the metabolic disposition of piperitenone (1) was examined in rats. Piperitenone (1) was administered orally (400 mg/kg of the b. wt./day) to rats for 5 days. The following urinary metabolites were isolated and identified by various spectral analyses: p-cresol (VI), 6,7-dehydromenthofuran (III), p-mentha-1,3,5,8-tetraen-3-ol (IX), p-mentha-1, 3,5-triene-3, 8-diol (X), 5-hydroxypiperitenone (VIII), 7-hydroxypiperitenone (XI), 10-hydroxypiperitenone (XII), and 4-hydroxypiperitenone (VII). Incubation of piperitenone (1) with phenobarbital-induced rat liver microsomes in the presence of NADPH resulted in the formation of five metabolites which have been tentatively identified as metabolites III, VII, VIll, XI, XII, on the basis of gas chromatography retention time and gas chromatography-mass spectrometry analysis. Based on these results, a probable mechanism for the formation of p-cresol from piperitenone (I) via the intermediacy of metabolite III has been proposed.

Manson MM, Ball HW, Barrett MC, Clark HL, Judah DJ, Williamson G, Neal GE. Mechanism of action of dietary chemoprotective agents in rat liver: induction of phase I and II drug metabolizing enzymes and aflatoxin B1 metabolism. Carcinogenesis 1997;18(9):1729-38.
A range of potential chemoprotective agents, most of them natural dietary constituents, has been examined for ability to modulate both phase I (cytochrome P450 1A1, 1A2, 2B1/2, 2C11, 2E1, 3A, 4A) and phase II drug metabolizing enzymes (glutathione S-transferases, in particular subunits Yc2 and P, aflatoxin B1-aldehyde reductase and quinone reductase) in rat liver. In addition to assays of total enzyme activity and Western blots for individual isozymes, the ability of microsomes to metabolize aflatoxin B1, and of cytosols to conjugate aflatoxin B1 (AFB1)-epoxide to GSH and to produce AFB1-dialcohol, were measured. Induction of gamma-glutamyl transpeptidase activity was examined by histochemistry. Differing patterns of induction were observed, reflecting differences in the control of expression of the individual enzymes studied. Of the compounds examined, butylated hydroxytoluene, ethoxyquin, indole-3-carbinol and phenethyl isothiocyanate were the most potent bifunctional agents (inducing both phase I and II activities). Oltipraz, while only weakly inducing CYP1A2 and 2B1/2, was a potent inducer of phase II enzymes. Caffeic acid, garlic oil, sinigrin and propyl gallate all showed some ability to induce phase II enzymes. 4-Methyl catechol, alpha-tocopherol and red wine decreased certain phase I enzyme activities, while inducing total GST activity. Butylated hydroxytoluene, ethoxyquin, garlic oil and indole-3-carbinol induced gamma glutamyltranspeptidase in periportal hepatocytes. Particularly because of their ability to induce the detoxifying activities of glutathione S-transferase Yc2 and aldehyde reductase, butylated hydroxytoluene, ethoxyquin, indole-3-carbinol, oltipraz, phenethyl isothiocyanate and sinigrin will be effective blocking agents in rodents, if administered prior to AFB1. While these studies indicate the relative contributions of phase I and II metabolism in the overall protective effect in rat, care should be taken that a similar balance is achieved in man, and that relevant enzymes or iso forms a e induced.

Martin N, Bardisa L, Pantoja C, Barra E, Demetrio C, Valenzuela J, Barrios M, Sepulveda MJ. Involvement of calcium in the cardiac depressant actions of a garlic dialysate. J Ethnopharmacol 1997;55(2):113-8.
In order to elucidate a possible role for calcium on the negative cardiotropic effects of a garlic (Allium sativum L., Liliaceae) dialysate in rat atria we studied: (a) the effects of our extract 15 min after preincubation with high and low concentrations of extracellular calcium ([Ca2+]o) on left and right activity of rat atria. The negative inotropism of garlic dialysate increased with calcium 0.75 mM; in contrast, high level of calcium (4.5 mM) induced a significant reduction of this depressant effect. None of these treatments modified the negative chronotropism of garlic; (b) nifedipine (10(-9) to 10(-7) M, verapamil (10(-9) to 10(-7) M) and diltiazem (10(-9) to 10(-7) M) induced a concentration-dependent synergism of the log concentration-effect of garlic dialysate on left atria. Verapamil and diltiazem (10(-7)M), but not nifedipine increased the inhibitory chronotropism of garlic in right atria; (c) negative inotropic and chronotropic effects demonstrated by nifedipine (1 x 10(-10) to 1.1 x 10(-6) M) were antagonized as expected by preincubation with Bay K-8644. Depressant actions of garlic were not modified with this pretreatment. These results suggest that the negative inotropic effect of our garlic dialysate is related to [Ca2+]o availability. It is possible that a restriction of intracellular calcium contributes to this effect. However, the negative chronotropic effect of garlic is scarcely affected by these modifications.

Matsuda H, Dai Y, Ido Y, Ko S, Yoshikawa M, Kubo M. Studies on kochiae fructus. III. Antinociceptive and antiinflammatory effects of 70% ethanol extract and its component, momordin Ic from dried fruits of Kochia scoparia L. Biol Pharm Bull 1997;20(10):1086-91.
The 70% ethanol extract (KS-ext) from Kochiae Fructus (dried fruits of Kochia scoparia L.) was screened for its activity on nociceptive and inflammatory responses in experimental animals. Although KS-ext at an oral administration of 500 mg/kg had an antinociceptive effect on writhing responses induced by acetic acid, it was ineffective on nociceptive response in the hot plate test. Oleanolic acid oligoglycoside, momordin Ic isolated from Kochiae Fructus significantly decreased the frequency of licking behavior within a unit of time at the late phase without affecting that of the early phase in the formalin test. Also, KS-ext inhibited the rise of vascular permeability induced by acetic acid, the increase of paw edema induced by carrageenin, histamine, serotonin or bradykinin and ear swelling induced by arachidonic acid. Momordin Ic also exhibited an inhibitory effect on carrageenin-induced edema. These results indicated that Kochiae Fructus has a peripheral antinociceptive effect mediated by antiinflammatory action, and that its active component can be partially attributed to momordin Ic.

Matsuda H, Dai Y, Ido Y, Murakami T, Matsuda H, Yoshikawa M, Kubo M. Studies on Kochiae Fructus. V. Antipruritic effects of oleanolic acid glycosides and the structure-requirement. Biol Pharm Bull 1998;21(11):1231-3.
We examined the antipruritic effects of various oleanolic acid glycosides from natural medicines such as Kochiae Fructus (the fruit of Kochia scoparia SCHRAD.) and Momordicae Radix (the roots of Momordica cochinchinensis SPRENG.) using a compound 48/80-induced pruritic model in mice. Oleanolic acid 3-O-monodesmosides showed an antipruritic effect, while oleanolic acid 3,28-O-bisdesmosides and their common sapogenol oleanolic acid lacked the activity. This evidence indicated that the 3-O-glycoside moiety and the 28-carboxyl group in oleanolic acid glycosides were essential for exhibiting the antipruritic effect. Furthermore, it was found that the 3-O-glucuronides showed more potent activity than the corresponding 3-O-glucosides.

Matsuda H, Li Y, Murakami T, Yamahara J, Yoshikawa M. Protective effects of oleanolic acid oligoglycosides on ethanol- or indomethacin-induced gastric mucosal lesions in rats. Life Sci 1998;63(17):L245-50.
We examined the effects of various oleanolic acid oligoglycosides obtained from traditional herbs on ethanol- or indomethacin-induced gastric mucosal lesions in rats and on gastric secretion in pylorus-ligated rats. Test samples were given orally to fasted rats 1 h before absolute ethanol (1.5 ml/rat, p.o.) or indomethacin (30 mg/kg, s.c.) treatment, or ligation of the pylorus. Oleanolic acid 3-O-monodesmosides [oleanolic acid 3-O-glucuronide (1, 20-50 mg/kg), momordin Ic (2, 5-50 mg/kg), and 28-O-deglucosyl-chikusetsusaponins IV (5, 10-50 mg/kg) and V (7, 10-50 mg/kg)] were found to show protective effects on ethanol-induced gastric mucosal lesions, whereas oleanolic acid 3,28-O-bisdesmosides [momordin IIc (3), chikusetsusaponins IV (4) and V (6)], oleanolic acid 28-O-monodesmoside [compound O (8)], and their common aglycon [oleanolic acid (9)] showed no such effects. Oleanolic acid 3-O-monodesmosides (1, 2, and 5) also showed protective effects on indomethacin-induced gastric mucosal lesions. 28-O-Deglucosyl-chikusetsusaponin V (7) did not inhibit the indomethacin-induced lesions, while chikusetsusaponins V (6, 50 mg/kg) had the gastroprotective effect. These active saponins (1, 2, 4-7, 10-50 mg/kg) did not decrease the gastric secretion by oral administration in pylorus-ligated rats.

Matsuda H, Tomohiro N, Yoshikawa M, Kubo M. Studies on Alismatis Rhizoma. II. Anti-complementary activities of methanol extract and terpene components from Alismatis Rhizoma (dried rhizome of Alisma orientale). Biol Pharm Bull 1998;21(12):1317-21.
A methanol extract (TMe-ext) from the dried rhizome of Alisma orientale was screened for anti-complementary activity in experimental models. In the animal models, it was found that TMe-ext inhibits zymosan-induced hind paw edema in rats and zymosan-activated rat serum (ZAS)-induced vascular permeability in mice. TMe-ext showed an inhibitory effect on complement-induced hemolysis through both the classical pathway and the alternative pathway. And TMe-ext inhibited hypotonic shock-induced hemolysis, but this effect was weak compared with the anti-complementary activities of TMe-ext. Four triterpenes (alisol A, alisol A monoacetate, alisol B and alisol B monoacetate) isolated from the rhizome also inhibited the complement-induced hemolysis through the classical pathway, but two sesquiterpenes (alismol and alismoxide) were ineffective. These results indicate that Alismatis Rhizoma shows anti-complementary activity, and its anti-complementary components are partially attributable to the terpene components mentioned above.

Matsumoto Y, Kato M, Tamada Y, Mori H, Ohashi M. Enhancement of interleukin-1 alpha mediated autocrine growth of cultured human keratinocytes by sho-saiko-to. Jpn J Pharmacol 1997;73(4):333-6.
We investigated the effects of Sho-saiko-to, the most commonly used herbal medicine in Japan, on the production of interleukin (IL)-1 alpha by cultured human epidermal keratinocytes. IL-1 alpha production was significantly promoted by treatment with 100 or 500 micrograms/ml Sho-saiko-to for 24 or 48 hr. Expression of IL-1 alpha receptors was the most markedly upregulated after treatment with 500 micrograms/ml Sho-saiko-to for 24 hr and with 100 or 500 micrograms/ml for 48 hr; these cells showed the characteristics of multilayered differentiated keratinocytes. The presence of an anti-IL-1 alpha antibody during the treatment with 500 micrograms/ml of Sho-saiko-to for 24 or 48 hr or with 100 micrograms/ml for 48 hr significantly down-regulated the synthesis by the keratinocytes and induced damages in them. Keratinocytes treated with Sho-saiko-to might produce IL-1 alpha and express IL-1 alpha receptors. IL-1 alpha may regulate the proliferation and differentiation of keratinocytes after Sho-saiko-to treatment. These findings suggest that Sho-saiko-to enhances the autocrine growth mediated by IL-1 alpha.

Matsuo K, Kobayashi M, Takuno Y, Kuwajima H, Yoshida T, et al . [Anti-tyrosinase activity of constituents of Arctostaphylos uva-ursi]. Yakugaku Zasshi 1997 Dec;117:1028-32. (Jpn)
IPA COPYRIGHT: ASHP The inhibitory effect on the activity of tyrosinase of different constituents, including 1,2,3,6-tetragalloylglucose (1,2,3,6-tetra-O-galloyl-beta-D-glucose), 1,2,3,4,6-pentagalloylglucose (1,2,3,4,6-penta-O-galloyl-beta-D-glucose), methyl gallate, gallic acid, and hydroquinone, of a methanolic extract of the leaves of Arctostaphylos uva-ursi was studied.

Mattei R, Dias RF, Espinola EB, Carlini EA, Barros SB. Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and antioxidants activity in vitro. J Ethnopharmacol 1998;60(2):111-6.
The effects on toxic and behavioral levels of guarana (Paullinia cupana) were assessed in rats and mice subsequent to acute and chronic administrations and were compared to those produced by Ginseng (Panax ginseng). Experimental parameters included tests for antioxidant capacity in vitro and measured in vivo, toxicological screening, progress in weight, motor activity, death rate, and histopathological examination of the viscera. Guarana showed an antioxidant effect because, even at low concentrations (1.2 microg/ml), it inhibited the process of lipid peroxidation. In high doses of 1000-2000 mg/kg (i.p. and p.o.) it did not induce significant alterations in parameters for toxicological screening. No effects on motor activity were observed, neither did guarana alter the hypnotic effect of pentobarbital. Ginseng (250-1000 mg/kg i.p.), however, elicited reductions in motor activity, eyelid ptosis and bristling fur. Consumption of liquids containing guarana or ginseng and progress in weight of the animals remained at levels similar to the controls, even after prolonged administration. The percentage mortality was equivalent in control and in treated groups. The absence of toxicity of guarana was also demonstrated by histopathological examination, with no alteration being detected in heart, lungs, stomach, small and large intestine, liver, pancreas, kidneys, bladder and spleen.

Maulik G, Maulik N, Bhandari V, Kagan VE, Pakrashi S, Das DK. Evaluation of antioxidant effectiveness of a few herbal plants. Free Radic Res 19997;27(2):221-8.
We have screened a number of plants from the Indian soil for potential antioxidant properties out of which fifteen extracts were found to be positive. Leaves/bulk from the plants were crushed and extracted with organic solvents by three different ways. The first group of plants were extracted with CHCL3:CH3OH (2:1), evaporated, partitioned between petroleum ether and methanol (9:1), aqueous methanolic part re-partitioned between methanol:H2O (4:1) and dichloromethane. Methanol was evaporated from the aqueous methanolic part and extracted with n-butanol. The second group of plants were extracted with methanol followed by partitioning between petroleum ether and CH3OH. The rest of the extraction procedure was the same as above. A third extraction procedure was used for Ocimum sanctum which after extraction with CHCL3:CH3OH (2:1), partitioned between CCL4 and CH3OH:H2O (9:1). Aqueous methanolic part was repartitioned between CH3OH:H2O (4:1) and CHCl3 and CHCl3 soluble part was used for the study. Free radical scavenging activities of the plant extracts were examined by chemiluminescence method. Peroxyl radical was generated from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), superoxide radical (O2-) from xanthine/xanthine oxidase (XO) and hydroxyl radical (OH) from Xanthine/XO/FeCl3/ EDTA. In addition, O2- and OH. scavenging activities were also determined by cytochrome C reduction and deoxyribose oxidation methods, respectively. The results of this study demonstrate that these plant extracts possess potent antioxidant activities.

Molck AM, Poulsen M, Tindgard Lauridsen S, Olsen P. Lack of histological cerebellar changes in Wistar rats given pulegone for 28 days. Comparison of immersion and perfusion tissue fixation. Toxicol Lett 1998;95(2):117-22.
Pulegone was given orally by gavage to groups of 28 SPF Wistar rats at dosage levels of 0 or 160 mg/kg body weight per day for 28 days. Clinically treated animals showed slackness, depression, decreased food consumption, and body weight. The loss of body weight was accompanied by a marked decrease in plasma creatinine. In contrast to earlier results, this study did not reveal occurrence of cyst-like spaces in the white matter of cerebellum using either perfusion or immersion tissue fixation techniques. Pulegone increased plasma alkaline phosphatase and relative liver weight indicating an adverse effect on the liver.

Moon A, Kim SH. Effect of Glycyrrhiza glabra roots and glycyrrhizin on the glucuronidation in rats. Planta Med 1997;63(2):115-9.
As an approach to elucidate the possible in vivo interaction of synthetic drugs and herbs which are frequently used in combination in Asia, the effect of Glycyrrhiza glabra on the metabolism of acetaminophen (AAP) was examined in male Sprague-Dawley rats. The pretreatment of the methanol extract of Glycyrrhiza glabra roots (Glycyrrhizae Radix, GR, 1 g/kg, p.o.) for 6 days significantly increased the cumulative biliary (156%) and urinary (132%) excretions of AAP-glucuronide conjugate within 120 min after the administration of AAP (150 mg/kg, i.v.) without affecting thioether and sulfate conjugates. These findings suggest that GR might enhance the glucuronidation pathway of AAP. In order to study the effect of GR on the glucuronidation in rat liver, we examined enzymatic activity of p-nitrophenol UDP-glucuronosyltransferase (UGT), which is also called UGT1A, and intracellular concentrations of hepatic UDP-glucuronic acid, upon the administration of GR (1 g/kg, p.o.) or glycyrrhizin (23 mg/kg, p.o.), a major component of GR, for 6 days. GR and glycyrrhizin caused increases in specific activities of UGT1A by 111% and 96%, respectively. Concentration of UDP-glucuronic acid was increased 257% by GR and 484% by glycyrrhizin. These data indicate that GR and glycyrrhizin activated glucuronidation and thus suggest the possibility that GR may influence detoxification of xenobiotics in rat liver. Using the p-nitrophenol UGT1A1 cDNA as a probe, we found that the activation of UGT1A by GR was not due to the induction of mRNAs for the enzyme.

Moreno L, Bello R, Beltran B, Calatayud S, Primo-Yufera E, Esplugues J. Pharmacological screening of different Juniperus oxycedrus L. extracts. Pharmacol Toxicol 1998;82(2):108-12.
Methanol and dichloromethanol extracts of leaves and stems of Juniperus oxycedrus have been tested for their toxicity, analgesic, antiinflammatory and central effects. Both extracts showed low acute toxicity and decreased spontaneous motility. The methanol extract exhibited an analgesic effect in models of chemical, mechanical and thermal stimulation whereas dichloromethanol extract showed only a significant effect in models of pain induced by chemical stimulation. Both extracts showed a significant antiinflammatory activity and inhibition of the rat paw oedema induced by carrageenin.

Motoyashiki T, Miyake M, Morita T, Mizutani K, Masuda H, Ueki H. Enhancement of the vanadate-stimulated release of lipoprotein lipase activity by astilbin from the leaves of Engelhardtia chrysolepis. Biol Pharm Bull 1998;21(5):517-9.
Astilbin, a dihydroflavonol rhamnoside isolated from the leaves of Engelhardtia chrysolepis, enhanced the vanadate-stimulated release of lipoprotein lipase (LPL) activity from rat isolated fat pads. N-[2-(Methyl-amino)ethyl]-5-isoquinolinesulfonamide (H-8), a potent inhibitor of cAMP-dependent protein kinase (PKA), markedly inhibited the enhancement by astilbin. Lipolysis in the fat pads was stimulated by astilbin alone in a dose-dependent manner and this stimulation was suppressed in the presence of vanadate, probably due to its antilipolytic action. A significant enhancement by astilbin was observed with increasing effects of vanadate on cAMP content in the fat pads and on cAMP phosphodiesterase (PDE) activity in the particulate fraction although astilbin alone showed only a slight increase in the cellular cAMP content and PDE activity. Astilbin may enhance the vanadate-stimulated release of LPL activity through a synergistic effect on an increase in the cellular cAMP content produced by vanadate accompanied by more potent activation of PKA.

Mukherjee S, Sur A, Maiti BR. Hepatoprotective effect of Swertia chirata on rat. Indian J Exp Biol 1997;35(4):384-8.
Present work was undertaken to ascertain the hepatoprotective effect of Swertia chirata in albino rats. Intraperitoneal injection of CCl4 (1 ml/kg body wt on every 72 hr. for 16 days) significantly increased serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and alkaline phosphatase (ALP) activities and bilirubin level in rat, but liver glycogen and serum cholesterol levels were decreased. Histologically it produced hepatocytic necrosis especially in the centrilobular region. Simultaneous treatments with S. Chirata (in different doses, viz, 20, 50 and 100 mg/kg body wt daily) and CCl4 (similar dose to that mentioned earlier) caused improvement at both biochemical and histopathological parameters compared to that of CCl4 treatment alone but it was most effective when S. chirata was administered in a moderate dose (50 mg/kg body wt).

Neary JT, Bu Y. Hypericum LI 160 inhibits uptake of serotonin and norepinephrine in astrocytes. Brain Res 1999;816(2):358-63.
Extracts of Hypericum perforatum, commonly known as St. John's wort, are frequently used in Germany and other European countries to treat mild to moderately severe depression, but the mechanism of antidepressant activity of Hypericum is not understood. Because known mechanisms of antidepressant activity include inhibition of serotonin and/or norepinephrine uptake, we investigated the effects of standardized extracts of Hypericum LI 160 on the transport of these monoamine neurotransmitters into astrocytes, cells which surround synaptic terminals and regulate neurotransmission by means of their uptake systems. We found that LI 160 inhibited both serotonin and norepinephrine uptake in a dose-dependent manner. The two monoamine transport systems were affected differently by LI 160: for serotonin, the main effect was a 50% decrease in the rate of maximal transport, whereas for norepinephrine, the main effect was a 4.5 fold reduction in the apparent affinity of norepinephrine for its uptake sites. Upon removal of LI 160, uptake was restored, thereby indicating that the inhibition was not due to a toxic effect of Hypericum on the cells. These findings suggest that the ability of LI 160 to inhibit serotonin and norepinephrine uptake may underlie the antidepressant activity of this Hypericum extract. Copyright 1999 Elsevier Science B.V.

Nijs PM. [Bio-active substances from nutrition and herbs: influence on the brain activity in children, elderly people and sportsmen]. Farm Tijdschr Belg 1997 Dec;74:16-29. (Dut)
IPA COPYRIGHT: ASHP An overview of secondary plant extracts, such as antihypoxidotics (Ginkgo biloba), adaptogenes (ginseng), phytosterols (in certain seeds and nuts), immunostimulators (Echinacea species), terpenes, organic fruity acids, and omega-3 fatty acids, that seem to exert an activity on the human brain function, is presented.

Nishimura N, Naora K, Hirano H, Iwamoto K. Effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of tolbutamide in rats. J Pharm Pharmacol 1998;50(2):231-6.
Although Sho-saiko-to (Xiao Chai Hu Tang), a major Chinese traditional medicine, is frequently prescribed with other synthetic or biotechnological drugs for the treatment of various chronic diseases, there is a dearth of information about interactions between sho-saiko-to and co-administered drugs. This paper reports the effects of Sho-saiko-to on the pharmacokinetics and glucose responses of a sulphonylurea hypoglycaemic agent, tolbutamide, after their oral administration in rats. After oral administration of tolbutamide (50 mg kg(-1)) with or without Sho-saiko-to extract powder (300 mg kg(-1)) to male Sprague-Dawley rats cannulated in the jugular vein, plasma tolbutamide and glucose levels were periodically measured. Co-administration of Sho-saiko-to tended to elevate the plasma tolbutamide concentration in the absorption phase. A two-compartment lag-time model was found to describe the plasma tolbutamide concentration-time data. The maximum concentration of tolbutamide was significantly increased and time to reach the maximum concentration was reduced to about 70% by co-administration with Sho-saiko-to. There was no significant change in area under the curve or in the elimination half-life of tolbutamide. The extent of the lowering effect of tolbutamide on plasma glucose levels was increased up to 0.75 h and decreased after 5 h after co-administration of Sho-saiko-to. In conclusion, these studies suggest that sho-saiko-to slightly hastens the gastrointestinal absorption of tolbutamide. Furthermore, it is considered that elevation of the gastrointestinal absorption rate by Sho-saiko-to might potentiate the hypoglycaemic effect of this sulphonylurea in the early period after oral administration.

O'Brien LW. Interactions and toxicities of drugs for HIV disease. Drug Ben Trends 1998 Jul 10;10:44-52.
IPA COPYRIGHT: ASHP An overview of the physiologic, genetic, and immunologic issues affecting the pharmacokinetics and pharmacodynamics of drugs prescribed for treating human immunodeficiency virus (HIV) and its related complications is presented, including toxicities associated with drugs frequently administered for HIV disease, drug interactions of commonly used agents to treat HIV disease, and medicinal herbs used by HIV-infected patients.

Oh KW, Kim HS, Wagner GC. Inhibitory effects of ginseng total saponin on methamphetamine-induced striatal dopamine increase in mice. Arch Pharmacal Res 1997;20(5):516-8.

Ohdo S, Ogawa N, Song JG, Higuchi S. Chronopharmacological study of KE-SI-TO components in mice. Life Sci 1998;62(22):2057-64.
Influence of dosing time on pharmacological effects and toxicity of KE-SI-TO (KST) components, as well as the role of each component in the circadian rhythms of KST, was investigated in ICR male mice under an LD (12:12) cycle. The mice given Cinnamomi Cortex (258 mg/kg, i.p.) or Paeoniae Radix (258 mg/kg, i.p.) showed a significant circadian rhythm in the time spent on the hot plate with the shortest latency at 0900 and the longest one at 0100 (p<0.01, respectively). The mice given Cinnamomi Cortex or Glycyrrhizae Radix (129 mg/kg, i.p.) showed a significant circadian rhythm with the lowest rectal temperature (RT) at 1700 and the highest one at 0500 (p<0.01, respectively). Cinnamomi Cortex (850 mg/kg, i.p.)- or Glycyrrhizae Radix (2500 mg/kg, i.p.)-induced toxicity showed a significant circadian rhythm with the highest mortality at 1700 and the lowest one at 0500 (p<0.05, respectively). The rhythmic patterns of the drug-induced analgesia, hypothermia and toxicity resembled the overall rhythms occurring after KST (1000 or 6000 mg/kg, i.p.) injection. These results suggest that the circadian rhythms in actions of Cinnamomi Cortex, Paeoniae Radix and Glycyrrhizae Radix are mainly responsible for the rhythm in the effects and toxicity of KST.

Ohta Y, Sasaki E, Nishida K, Kongo M, Hayashi T, Nagata M, Ishiguro I. Inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on hepatic triglyceride accumulation with the progression of carbon tetrachloride-induced acute liver injury in rats. J Ethnopharmacol 1998;61(1):75-80.
The inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on hepatic triglyceride (TG) accumulation with the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). TJ-15 at a dose of 100, 250 or 500 mg/kg body weight (BW) was orally administered to male Wistar rats aged 7 weeks, 6 h after the intraperitoneal injection of CCl4 (1.0 ml/kg BW) at which time apparent liver injury and hepatic TG accumulation occurred. TJ-15 significantly prevented not only the progression of liver injury but also inhibited hepatic TG accumulation with the progression of the injury in a dose-dependent manner when these effects were examined 24 h after CCl4 injection. In CCl4-untreated rats with oral administration of TJ-15 at a dose of 100, 250 or 500 mg/kg BW, liver and serum TG concentrations decreased depending on the dose of the herbal medicine. These results indicate that in rats intoxicated once with CCl4, orally administered TJ-15 can inhibit hepatic TG accumulation with the progression of acute liver injury by its decreasing action on serum and liver TG levels, leading to a prevention of the progression of the liver injury.

Panossian AG, Oganessian AS, Ambartsumian M, Gabrielian ES, Wagner H, Wikman G. Effects of heavy physical exercise and adaptogens on nitric oxide content in human saliva. Phytomedicine 1999;6(1):17-26.
Since heavy physical exercise increases the content of nitric oxide and cortisol in blood and saliva, standardized extracts of the adaptogen herbal drugs Schizandra chinensis and Bryonia alba roots were applied to several groups of athletes in a placebo controlled double blind study. In the beginning of a test with athletes Schizandra chinensis and Bryonia alba extracts increased the concentration of NO and cortisol in blood plasma and saliva similar to athletes with heavy physical exercise. These results correlate with an increased physical performance in athletes taking adaptogens versus athletes taking placebo. In contrast after treatment with the adaptogen heavy physical exercise does not increase salivary NO and cortisol in athletes, whereas athletes treated with placebo heavy physical exercise increased salivary NO. These results show that the salivary NO test can be used both for evaluation of physical loading and stress protective effect of an adaptogen.

Park JA, Kim KW, Kim SI, Lee SK. Caspase 3 specifically cleaves p21WAF1/CIP1 in the earlier stage of apoptosis in SK-HEP-1 human hepatoma cells. Eur J Biochem 1998;257(1):242-8.
We report here that p21WAF1/CIP1, an inhibitor of cyclin kinases, underwent proteolytic processing into a smaller fragment, p14, in the early stage of apoptosis in SK-HEP-1 cells. Apoptosis was induced by either staurosporine or ginsenoside Rh2, a ginseng saponin with a dammarane skeleton. Proteolytic processing was the result of caspase-3 activity, which accompanied the early changes in cell morphology and DNA fragmentation. p21WAF1/CIP1 translated in vitro was cleaved into a p14 fragment when incubated with cell extracts obtained from either ginsenoside Rh2-treated or staurosporine-treated cells. Cleavage was equally inhibited in both cases by adding Ac-DEVD-CHO, a specific caspase-3 inhibitor, but not by Ac-YVAD-CHO, a specific caspase-1 inhibitor. Similarly, p21WAF1/CIP1 was efficiently cleaved by recombinant caspase-3, overexpressed in Escherichia coli. Moreover, the endogenous p21WAF1/CIP1 of untreated cell extracts was also cleaved by recombinant caspase 3, as measured by immunoblotting. Mutation analysis allowed identification of two caspase-3 cleavage sites, DHVD112/L and SMTD149/F, which are located within or near the interaction domains for cyclins, Cdks, and proliferating cell nuclear antigen (PCNA). Taken together, these results show that ginsenoside Rh2 and staurosporine increase caspase-3 activity, which in turn directly cleaves p21WAF1/CIP1 during the early stages of apoptosis. We propose that proteolytic cleavage of p21WAF1/CIP1 is a functionally relevant event that allows release of the cyclin/Cdk complex from the p21WAF1/CIP1 inhibitor, resulting in the elevated levels of cyclin/Cdk kinase activity seen in the earlier stage of apoptosis.

Park JA, Lee KY, Oh YJ, Kim KW, Lee SK. Activation of caspase-3 protease via a Bcl-2-insensitive pathway during the process of ginsenoside Rh2-induced apoptosis. Cancer Lett 1997;121(1):73-81.
We have demonstrated that ginsenoside Rh2 (G-Rh2), a ginseng saponin with a dammarane skeleton, induces apoptosis of human hepatoma SK-HEP-1 cells as evidenced by analyses of DNA fragmentation, flow cytometry and changes in cell morphology. Ac-YVAD-CMK or Ac-DEVD-CHO effectively prevented G-Rh2-induced DNA fragmentation, indicating the involvement of caspase-like proteases in the process of apoptosis. In addition, G-Rh2 induced the processing of caspase-3 to an active form, p17. In stable Bcl-2 transfectants, G-Rh2 also induced DNA fragmentation, while staurosporine-induced DNA fragmentation was totally blocked. As it did in wild-type cells, G-Rh2 induced the proteolytic activation of caspase-3 protease and subsequent cleavage of PARP in the bcl-2 transfectants. In summary, G-Rh2 contains an apoptotic inducing activity in SK-HEP-1 cells which functions via Bcl-2-insensitive activation of caspase-3, followed by proteolytic cleavage of PARP.

Premalatha B, Sujatha V, Sachdanandam P. Modulating effect of Semecarpus anacardium Linn. nut extract on glucose metabolizing enzymes in aflatoxin B1-induced experimental hepatocellular carcinoma. Pharmacol Res 1997;36(3):187-92.
The herbal remedy extended by Semecarpus anacardium nut extract against Aflatoxin B1 mediated hepatocellular carcinoma was established by studies on carbohydrate metabolizing enzymes. Since some definite correlation exists between tumour progression and the activities of glycolytic and gluconeogenic enzymes, assessment of alterations in their activity can be used as successful markers of diagnosis and prognosis. The present work compares the activities of glycolytic and gluconeogenic enzymes in hepatocellular carcinoma bearing rats with drug-treated animals. An overall increase in glycolytic enzymes namely hexokinase, phosphoglucoisomerase, and aldolase with a subsequent reduction in gluconeogenic enzymes, glucose-6-phosphatase and fructose-1,6-biphosphatase was observed in plasma and liver homogenates of hepatocellular carcinoma bearing rats. The administration of Semecarpus anacardium nut extract caused a significant decrease in the activity of glycolytic enzymes and an increase in gluconeogenic enzymes' activities to near normal values in drug-treated animals. Copyright 1997 The Italian Pharmacological Society.

Preuss HG, Jarrell ST, Scheckenbach R, Lieberman S, Anderson RA. Comparative effects of chromium, vanadium and gymnema sylvestre on sugar-induced blood pressure elevations in SHR. J Am Coll Nutr 1998;17(2):116-23.
OBJECTIVE: Effects on systolic blood pressure (SBP) of ingesting three agents reported to influence insulin metabolism, i.e., chromium polynicotinate, bis(maltolato)oxovanadium (BMOV), and the herb, Gymnema sylvestre, were assessed simultaneously in spontaneously hypertensive rats (SHR). METHODS: In the first study, SHR were fed either a starch, sugar, or sugar diet containing chromium polynicotinate, bis(maltolato)oxovanadium (BMOV), or G. sylvestre. Tail SBP was estimated indirectly and various blood chemistries were measured. TBARS formation was determined in hepatic and renal tissue. In a second study, tail SBP was measured in SHR ingesting diets containing different concentrations of BMOV. RESULTS: Compared to starch, SHR consuming sucrose showed a significant elevation of SBP within days that was maintained for the duration of study. Addition of chromium polynicotinate to the sucrose diet at the beginning of study prevented the sucrose-induced elevation of SBP for 2 weeks, but SBP rose significantly after that. BMOV at high concentrations overcame the sucrose-induced rise in SBP and even decreased SBP below values seen in SHR eating the starch diet, but marked weight loss was noted. A second study examined different concentrations of BMOV. At 0.01% w/w concentration of BMOV, SBP was still significantly decreased, even though SHR did not lose body weight (BW) early on. SHR consuming G. sylvestre showed no change or even elevated SBP. Hepatic thiobarbituric acid reacting substances (TBARS) formation, an estimate of lipid peroxidation, was decreased by chromium polynicotinate and BMOV, and renal TBARS by chromium polynicotinate. Circulating cholesterol concentrations were decreased in the SHR consuming G. sylvestre. CONCLUSIONS: Chromium decreases the portion of SBP elevated by high sucrose intake as shown previously, but high levels of sucrose ingestion can eventually overcome this. BMOV overcame sucrose-induced elevation of SBP as well as some of the "genetic hypertension." Different from chromium, this decrease was not overcome by high levels of dietary sucrose. The significant lowering of cholesterol with G. sylvestre ingestion indicates some effect on metabolism, but G. sylvestre did not lower and even raised SBP.

Puig L. Pharmacodynamic interaction with phototoxic plants during PUVA therapy [letter]. Br J Dermatol 1997;136(6):973-4.

Qi J, Toyoshima A, Honda Y, Mineshita S. Pharmacokinetic study on acetaminophen: interaction with a Chinese medicine. J Med Dent Sci 1997;44(1):31-5.
To know the influences of a Chinese traditional medicine (KAKKONTO) on the metabolism of acetaminophen (APAP), we have carried out pharmacokinetic studies on APAP under KAKKONTO coadministration in humans and rats. In humans, the pharmacokinetic parameters were calculated from the blood APAP concentration-time curves of each volunteer. The parameters did not show any significant differences between the KAKKONTO-coadministration group (group K) and the APAP-administration group (group A). KAKKONTO, when given at two different doses, did not show any significant effects on blood APAP level. In rats, the blood APAP level was significantly higher than that of group A (p < 0.01) only in the 100 mg/kg of group K at 0.25 h after APAP administration. There were no other significant differences.

Rabinkov A, Miron T, Konstantinovski L, Wilchek M, Mirelman D, Weiner L. The mode of action of allicin: trapping of radicals and interaction with thiol containing proteins. Biochim Biophys Acta 1998;1379(2):233-44.
BIOSIS COPYRIGHT: BIOL ABS. Allicin (thio-2-propene-1-sulfinic acid S-allyl ester) is the main biologically active component of garlic clove extracts. Its biological activity was attributed to either antioxidant activity or thiol disulfide exchange. Antioxidant properties of both allicin and its precursor, alliin (+ S-allyl-L-cysteine sulfoxide), were investigated in the Fenton oxygen-radical generating system (H2O2-Fe(II)). Using the spin trapping technique and ESR, it was found that both compounds possessed significant antioxidant activity. The reaction between allicin and L-cysteine was studied by 1H and 13C-NMR, and a S-thiolation product, S-allylmercaptocysteine, was identified. Allicin irreversibly inhibited SH-protease papain, NADP+-dependent alcohol dehydrogenase from Thermoanaerobium brockii (TBAD), and the NAD+-dependent alcohol dehydrogenase from horse liver (HLAD). All the three enzymes could be reactivated with thiol containing compounds. Papain could be reactivated with glutathione, TBAD with dithiothreitol or 2-mercaptoethanol (2-ME) but not by glutathione, while HLAD could be reactivated only with 2-ME. This study demonstrates that in addition to its antioxidant activity, the major biological effect of allicin should be attributed to its rapid reaction with thiol containing proteins.

Rohnert U, Koske D, Schneider W, Elstner EF. Inhibition by Salix- extracts and Phytodolor of copper-catalyzed oxidative destruction. Z Naturforsch [C] 1998;53(3-4):233-40.
Oxidation of low density lipoprotein (LDL) by copper ions is strongly inhibited by different aqueous extracts (Salix spec (SE); Fraxinus-Dolidago-Populus (Phytodolor)(PD) in a concentration range between 4 and 7 micrograms/ml. 10 to 50 microM salicylic acid (SA) stimulate LDL-oxidation whereas higher concentrations (10 to 500 micromM) showed no effect. Likewise ethene release from 2-keto-4-methylthiobutyrate (KMB) is strongly inhibited by the above extracts in a reaction driven by dihydroxyfumarate (DHF) in the presence of copper ions. This system may represent some features of the diabetic situation where DHF as an endiole may stand for certain Amadori products. In order to find out whether the inhibitory effects are due to copper chelation we tested the copper-dependent conversion of photodynamic ethane release from alpha-linolenic acid into ethene formation. Copper chelation is apparently only partially involved in inhibition of copper-dependent oxidations and only at a certain concentration of extracts from salix spec (SE) or extracts from Fraxinus-Solidago-Populus (Phytodolor)(PD).

Romano EL, Montano RF, Brito B, Apitz R, Alonso J, Romano M, Gebran S, Soyano A. Effects of Ajoene on lymphocyte and macrophage membrane-dependent functions. Immunopharmacol Immunotoxicol 1997;19(1):15-36.
Ajoene, (E, Z) -4, 5, 9-trithiadeca-1, 6, 11-triene 9 oxide, is a compound originally isolated from ethanolic extracts of garlic that impairs platelet aggregation by inhibiting the functional exposure of platelet integrins GPIIb/IIIa. In vitro, Ajoene is toxic for several tumoral cell lines, and exert an antiproliferative effect on T. cruzi and murine malaria parasites. Here we show that Ajoene strongly inhibited the proliferation induced in human lymphocytes by the mitogens phytohemagglutinin (PHA), phorbol myristate acetate (PMA) and anti-CD3, and the capping formation induced in B lymphocytes by anti-IgM antibodies. On macrophages, Ajoene was also found to partially inhibit the lypopolysaccharide-induced production of Tumor Necrosis Factor (TNF), and to decrease the phagocytic activity of thioglycolate-elicited mouse peritoneal macrophages for IgG-opsonized, human erythrocytes. Ajoene also partially prevented the lytic effect of human and rabbit TNF on Actinomycin D-treated WEHI 164 cells. These results strongly suggest that Ajoene is a potent modulator of membrane-dependent functions of immune cells.

Roth GN, Chandra A, Nair MG. Novel bioactivities of Curcuma longa constituents. J Nat Prod 1998;61(4):542-5.
Bioassay-directed fractionation of ethyl acetate extract from Curcuma longa Linn. rhizomes yielded three curcuminoids, which displayed topoisomerase I and II enzyme inhibition activity. Curcumin III (3) was the most active curcuminoid, inhibiting topoisomerase at 25 micrograms mL-1. Curcumin I (1) and curcumin II (2) inhibited the topoisomerases at 50 micrograms mL-1. Fractionation of the volatile oil from the rhizomes afforded ar-turmerone (4), which displayed mosquitocidal activity with an LD100 of 50 micrograms mL-1 on Aedes aegyptii larvae. Bioassay-directed fractionation of hexane extract from the turmeric leaves yielded labda-8(17),12-diene-15,16 dial (5) with antifungal activity against Candida albicans at 1 micrograms mL-1 and inhibited the growth of Candida kruseii and Candida parapsilosis at 25 micrograms mL-1. In addition, 5 displayed 100% mosquitocidal activity on A. aegyptii larvae at 10 micrograms mL-1.

Ryu BK, Ahn BO, Oh TY, Kim SH, Kim WB, Lee EB. Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophen- and CCl4-induced liver damage in rats. Arch Pharm Res 1998;21(5):508-13.
The hepatoprotective effect of DA-9601, a quality-controlled extract of Artemisia asiatica, on liver damage induced by acetaminophen (APAP) and carbon tetrachloride (CCl4) was investigated by means of serum-biochemical, hepatic-biochemical, and histopathological examinations. Doses of DA-9601 (10, 30, or 100 mg/kg) were administered intragastrically to each rat on three consecutive days i.e. 48 h, 24 h and 2 h before a single administration of APAP (640 mg/kg, i.p.) or CCl4 (2 ml/kg, p.o.). Four h and 24 h after hepatotoxin treatment, the animals were sacrificed for evaluation of liver damage. Pretreatment of DA-9601 reduced the elevation of serum ALT, AST, LDH and histopathological changes such as centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration dose-dependently. DA-9601 also prevented APAP- and CCl4-induced hepatic glutathione (GSH) depletion and CCl4-induced increase of hepatic malondialdehyde (MDA), a parameter of lipid peroxidation, in a dose-dependent manner. These findings suggest that pretreatment with DA-9601 may reduce chemically induced liver injury by complex mechanisms which involve prevention of lipid peroxidation and preservation of hepatic GSH.

Ryu JH, Lee HJ, Jeong YS, Ryu SY, Han YN. Yomogin, an inhibitor of nitric oxide production in LPS-activated macrophages. Arch Pharm Res 1998;21(4):481-4.
In activated macrophages the inducible form of nitric oxide synthase (i-NOS) generates high amounts of toxic mediator, nitric oxide (NO) which contributes to the circulatory failure associated with septic shock. A sesquiterpene lactone compound (yomogin) isolated from medicinal plant Artemisia princeps Pampan inhibited the production of NO in LPS-activated RAW 264.7 cells by suppressing i-NOS enzyme expression. Thus, yomogin may be a useful candidate for the development of new drugs to treat endotoxemia and inflammation accompanied by the overproduction of NO.

Satoh K, Nagai F, Ushiyama K, Yasuda I, Seto T, Kano I. Inhibition of Na+,K(+)-ATPase by 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, a major constituent of both moutan cortex and Paeoniae radix. Biochem Pharmacol 1997;53(4):611-4.
The inhibition of Na+,K(+)-ATPase activity by various constituents of Moutan Cortex and Paeoniae Radix was studied. 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose (PGG), a major component of both crude drugs, strongly inhibited Na+,K(+)-ATPase activity (IC50 = 2.5 x 10(-6) M), whereas galloylpaeoniflorin, benzoic acid, and catechin were weakly inhibitory, and albiflorin, oxypaeoniflorin, paeoniflorin, paconol, and phenol were ineffective. The inhibition of Na+,K(+)-ATPase activity by PGG was decreased in the presence of BSA or phospholipids. The inhibition mode of PGG was noncompetitive with respect to ATP. The K0.5 value for Na+ was increased by the addition of PGG from 9.1 to 12.3 mM, whereas that for K+ was not altered. PGG also inhibited K(+)-dependent p-nitrophenyl phosphatase activity with an IC50 value of 5.3 x 10(-6) M, and the extent of the inhibition increased at higher concentrations of K+. The K0.5 value for K+ was decreased by the addition of PGG from 3.3 to 2.0 mM. These results suggested that the inhibition of Na+,K(+)-ATPase activity is caused by interaction of PGG with the enzyme in the E2 state. The inhibitory effect of Moutan Cortex or Paeoniae Radix is considered to be mainly attributable to PGG.

Schempp H, Denke A, Mann E, Schneider W, Elstner EF. Biochemical activities of extracts from Hypericum perforatum L. 3rd Communication: modulation of peroxidase activity as a simple method for standardization. Arzneimittelforschung 1999;49(2):115-9.
Alcoholic extracts from the herb "St. John's wort" (Hypericum perforatum L.) are widely used to counteract depressive situations, where the question on the mainly active principle is still under discussion. Thus, standardization of the drug on the basis of dry matter has been chosen instead of the popular leading component, hypericin. Inhibition of myeloperoxidase-catalyzed dimerization of enkephalins by Hypericum extracts has recently been reported. This method is based on the separation and quantification of enkephalin dimers by HPLC. In order to simplify this assay myeloperoxidase could be substituted by the cheaper horseradish peroxidase and the enkephalins by the amino acid tyrosine without loss of significance. In this communication we represent a more rapid photometric method based on peroxidase-catalyzed indole acetic acid oxidation suitable for quick, simple and economic drug standardization.

Schliebs R, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl V. Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain. Neurochem Int 1997;30(2):181-90.
Although some promising results have been achieved by acetylcholinesterase inhibitors, an effective therapeutic intervention in Alzheimer's disease still remains an important goal. Sitoindosides VII-X, and withaferin-A, isolated from aqueous methanol extract from the roots of cultivated varieties of Withania somnifera (known as Indian Ginseng), as well as Shilajit, a pale-brown to blackish brown exudation from steep rocks of the Himalaya mountain, are used in Indian medicine to attenuate cerebral functional deficits, including amnesia, in geriatric patients. The present investigation was conducted to assess whether the memory-enhancing effects of plant extracts from Withania somnifera and Shilajit are owing to neurochemical alterations of specific transmitter systems. Therefore, histochemistry to analyse acetylcholinesterase activity as well as receptor autoradiography to detect cholinergic, glutamatergic and GABAergic receptor subtypes were performed in brain slices from adult male Wistar rats, injected intraperitoneally daily with an equimolar mixture of sitoindosides VII-X and withaferin-A (prepared from Withania somnifera) or with Shilajit, at doses of 40 mg/kg of body weight for 7 days. Administration of Shilajit led to reduced acetylcholinesterase staining, restricted to the basal forebrain nuclei including medial septum and the vertical limb of the diagonal band. Systemic application of the defined extract from Withania somnifera, however, led to differential effects on AChE activity in basal forebrain nuclei: slightly enhanced AChE activity was found in the lateral septum and globus pallidus, whereas in the vertical diagonal band AChE activity was reduced following treatment with sitoindosides VII-X and withaferin-A. These changes were accompanied by enhanced M1-muscarinic cholinergic receptor binding in lateral and medial septum as well as in frontal cortices, whereas the M2-muscarinic receptor binding sites were increased in a number of cortical regions including cingulate, frontal, piriform, parietal and retrosplenial cortex. Treatment with Shilajit or the defined extract from Withania somnifera affected neither GABAA and benzodiazepine receptor binding nor NMDA and AMPA glutamate receptor subtypes in any of the cortical or subcortical regions studied. The data suggest that Shilajit and the defined extract from Withania somnifera affect preferentially events in the cortical and basal forebrain cholinergic signal transduction cascade. The drug-induced increase in cortical muscarinic acetylcholine receptor capacity might partly explain the cognition-enhancing and memory-improving effects of extracts from Withania somnifera observed in animals and humans.

Siegers CP, Robke A, Pentz R. Effects of garlic preparations on superoxide production by phorbol ester activated granulocytes. Phytomedicine 1999;6(1):13-6.
Sulfur containing constituents of garlic are considered responsible for conveying the antioxidative properties of garlic preparations. The radical scavenging properties of garlic preparations against oxygen radicals, specifically their ability to inhibit the formation of superoxide anions, were investigated using human granulocytes activated with 10 nM phorbol myristyl acetate (PMA). A garlic powder preparation inhibited the production of superoxide with a calculated IC50 of 390 micrograms/ml. An 8-10% alliin enriched garlic extract (alliinase inactivated) did not inhibit superoxide production even at concentrations as high as 1000 micrograms/ml. When the extract was mixed with garlic powder (90% garlic powder, 10% garlic extract), there was a clear inhibition of superoxide production with an IC50 value of 295 micrograms/ml. An even stronger inhibitory effect could be achieved when garlic powder was added to garlic extract (10% garlic powder, 90% extract, IC50 = 160 micrograms/ml). These experimental results suggest that the alliin metabolite allicin may be responsible for the oxygen radical scavenging properties of garlic.

Siess MH, Le Bon AM, Canivenc-Lavier MC, Suschetet M. Modification of hepatic drug-metabolizing enzymes in rats treated with alkyl sulfides. Cancer Lett 1997;120(2):195-201.
Natural compounds which elevate detoxification enzymes and/or reduce activating enzymes could be considered as good candidates to protect against cancer. In this work, we studied the modulation of hepatic drug-metabolizing enzymes in rats treated with dimethyl sulfide (DMS), dimethyl disulfide (DMDS), methylpropyl disulfide (MPDS), dipropyl sulfide (DPS), dipropyl disulfide (DPDS) and diallyl disulfide (DADS) issued from Allium species. Compounds containing methyl groups had little or no effect. Compounds with two propyl groups or two allyl groups provoked a pleiotropic response on drug-metabolizing enzymes. DPS, DPDS and DADS induced ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase and mostly pentoxyresorufin O-depentylase and decreased nitrosodimethylamine N-demethylase and erythromycin N-demethylase. These modifications of enzyme activities were accompanied by an increase of CYP 2B1,2 and a decrease of CYP 2E1, evidenced by immunoblotting. The same treatments stimulated some phase II enzyme activities such as glutathione transferase and UDP-glucuronyl transferases. This pattern of induction and/or inhibition of drug metabolizing enzymes was qualitatively similar to that elicited by the enzyme inducer, phenobarbital. The magnitude of the effects produced by DPDS was smaller than those produced by DADS and DPS. Our results suggest a possible protective effect of alkyl sulfides as well as diallyl disulfide, on the first step of carcinogenesis via the modulation of enzymes involved in carcinogen metabolism.

Singh A, Singh SP. Modulatory potential of smokeless tobacco on the garlic, mace or black mustard-altered hepatic detoxication system enzymes, sulfhydryl content and lipid peroxidation in murine system. Cancer Lett 1997;118(1):109-14.
The present study evaluates the potential of smokeless tobacco to modify the chemopreventive efficacy of minor dietary constituents, including garlic, mace or black mustard, via modulating the competing pathways of hepatic detoxication system and antioxidant defense mechanism in murine system. Garlic (100 mg/kg b.w. per day) by gavage and mace (1% w/w) or black mustard (1% w/w) in diet induced a significant increase in the levels of glutathione-S-transferase (GST), acid-soluble sulfhydryl (-SH), cytochrome b5 (Cyt.b5) and cytochrome P-450 (Cyt.P-450) in murine liver. The hepatic levels of GST and -SH were significantly depressed whereas microsomal Cyt.b5, Cyt.P-450 and MDA levels were elevated in groups treated with smokeless tobacco (50 or 100 mg/kg b.w. per day). The data revealed the inhibitory potential of smokeless tobacco on garlic-induced hepatic GST/GSH system besides the significant augmentation by smokeless tobacco on garlic or mace or black mustard-induced microsomal cytochromes. The possible implications of modulation in competing bioactivation and detoxication pathways in the process of chemical carcinogenesis are discussed.

Song K, Milner JA. Heating garlic inhibits its ability to suppress 7, 12-dimethylbenz(a)anthracene-induced DNA adduct formation in rat mammary tissue. J Nutr 1999;129(3):657-61.
The present studies compared the impact of heating, either by microwave or convection oven, on the ability of garlic to reduce the in vivo bioactivation of 7,12-dimethylbenz(a)anthracene (DMBA) in 55-d-old female Sprague-Dawley rats. In study 1, rats were fed a semipurified casein-based diet and treated by gastric gavage thrice weekly for 2-wk with crushed garlic (0.7 g in 2 mL corn oil) or the carrier prior to DMBA treatment (50 mg/kg body weight). Providing crushed garlic reduced by 64% (P < 0.05) the quantity DMBA-induced DNA adducts present in mammary epithelial cells compared to controls. In study 2, microwave treatment for 60 s, but not 30 s, decreased (P < 0.05) the protection provided by garlic against DMBA-induced adduct formation. In study 3, allowing crushed garlic to stand for 10 min prior to microwave heating for 60 s significantly (P < 0.05) restored its anticarcinogenic activity. Microwave heating of garlic for 30 s resulted in a 90% loss of alliinase activity. Heating in a convection oven (study 4) also completely blocked the ability of uncrushed garlic to retard DMBA bioactivation. Study 5 revealed that providing either 0.105 micromol diallyl disulfide or S-allyl cysteine by gastric gavage thrice weekly for 2 wk was effective in retarding DMBA bioactivation but isomolar alliin was not. These studies provide evidence that alliinase may be important for the formation of allyl sulfur compounds that contribute to a depression in DMBA metabolism and bioactivation.

Sonoda Y, Kasahara T, Mukaida N, Shimizu N, Tomoda M, Takeda T. Stimulation of interleukin-8 production by acidic polysaccharides from the root of Panax ginseng. Immunopharmacology 1998;38(3):287-94.
The root of Panax ginseng C.A. Meyer, is a well-known important Chinese traditional medicine used as a stomachic, tonic, sedative and as an elixir called Ginseng in China and Japan. The precise mechanism of the biological actions of this plant is not fully understood. In order to elucidate the immunomodulating activities of this plant, we examined the direct effects of four of its components, acidic polysaccharides isolated in previous studies, on cytokine (interleukin-8; IL-8) production by a human monocytic cell line, THP-1, and human blood monocytes in vitro, as IL-8 is a potent inflammatory cytokine involved in neutrophil chemotaxis and activation. We found that one component, ginsenan S-IIA, is a potent inducer of IL-8 production by human monocytes and THP-1 cells, and this induction is accompanied by increased IL-8 mRNA expression.

Sovova M, Fiserova J, Sova J, Opletal L. [Pharmaceutical significance of the species of the genus Solidago. Part 1. Glycosides of Solidago virgaurea L.]. Ceska Slov Farm 1998;47(3):103-9. (Cze)

Stanic G, Gavric D, Brkic D, Plazibat M. [Elymus repens (L.) Gould and Cynodon dactylon (L.) Pers.--botanical and pharmacologic data]. Farm Glas 1997 Dec;53:369-77. (Scr)

Sumioka I, Matsura T, Kasuga S, Itakura Y, Yamada K. Mechanisms of protection by S-allylmercaptocysteine against acetaminophen-induced liver injury in mice. Jpn J Pharmacol 1998;78(2):199-207.
S-Allylmercaptocysteine (SAMC), one of the water-soluble organosulfur compounds in ethanol extracts of garlic (Allium sativum L.), has been shown to protect mice against acetaminophen (APAP)-induced liver injury. In this study, we examined the mechanisms underlying this hepatoprotection. SAMC (100 mg/kg, p.o.) given 2 and 24 hr before APAP administration (500 mg/kg, p.o.) suppressed the plasma alanine aminotransferase activity increases 3 to 12 hr after APAP administration significantly. The hepatic reduced glutathione levels of vehicle-pretreated mice decreased 1 to 6 hr after APAP administration, but SAMC pretreatment suppressed the reductions 1 to 6 hr after APAP administration significantly. These inhibitory effects of SAMC were dose-dependent (50-200 mg/kg) 6 hr after APAP administration. As SAMC pretreatment (50-200 mg/kg) suppressed hepatic cytochrome P450 2E1-dependent N-nitrosodimethylamine demethylase activity significantly in a dose-dependent manner, we suggest that one of its protective mechanisms is inhibition of cytochrome P450 2E1 activity. SAMC pretreatment also suppressed the increase in hepatic lipid peroxidation and the decrease in hepatic reduced coenzyme Q9 (CoQ9H2) levels 6 hr after APAP administration. The hepatic CoQ9H2 content of the SAMC pretreatment group was maintained at the normal level. Therefore, we suggest that another hepatoprotective mechanism of SAMC may be attributable to its antioxidant activity.

Tao X, Schulze-Koops H, Ma L, Cai J, Mao Y, Lipsky PE. Effects of Tripterygium wilfordii hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production. Arthritis Rheum 1998;41(1):130-8.
OBJECTIVE. Extracts of the Chinese herbal remedy Tripterygium wilfordii Hook F (TWHF) have been reported to be effective in the treatment of patients with a variety of inflammatory and autoimmune diseases, but the mechanism of this therapeutic effect has not been completely delineated. The present study was designed to assess the effects of TWHF on the in vitro synthesis of prostaglandin E2 (PGE2) and on the expression of the cyclooxygenase isoforms, COX-1 and COX-2, in various human cell types. METHODS. Monocytes from human peripheral blood (HM), fibroblasts from rheumatoid arthritis synovial tissue (RASF), human neonatal foreskin fibroblasts (HFF), and the histiocytic cell line U937 were cultured for designated time periods with or without lipopolysaccharide (LPS), and in the presence or absence of varying concentrations of the following inhibitors: the methanol/chloroform (T2) extract of TWHF, the ethyl acetate (EA) extract of TWHF, a purified diterpenoid component of TWHF (triptolide), dexamethasone, and indomethacin. Culture supernatants were harvested for PGE2 content assays. Total RNA was extracted from the cells and analyzed for COX-1 and COX-2 messenger RNA (mRNA) expression using reverse transcriptase-polymerase chain reaction or Northern blotting. RESULTS. Both the T2 and EA extracts inhibited PGE2 synthesis in the LPS-stimulated HM, RASF, and HFF cells, which was reflected by a marked suppression in the levels of mRNA for COX-2. In contrast, neither extract inhibited PGE2 production in U937 cells that did not express COX-2. Triptolide also inhibited LPS-stimulated induction of COX-2 mRNA and synthesis of PGE2, at the same inhibitory concentration as seen with the EA extract. The effects of T2, EA, and triptolide paralleled the inhibitory action of dexamethasone. CONCLUSION. The data indicate that both the T2 and EA extracts of TWHF, as well as the triptolide component, inhibit PGE2 production in a variety of human cells by blocking the up-regulation of COX-2.

Teng L, Crooks PA, Dwoskin LP. Lobeline displaces [3H]dihydrotetrabenazine binding and releases [3H]dopamine from rat striatal synaptic vesicles: comparison with d-amphetamine. J Neurochem 1998;71(1):258-65.
Lobeline, an alkaloid from Indian tobacco (Lobelia inflata), is classified as a nicotinic agonist and is currently used as a smoking cessation agent. However, our previous in vitro studies demonstrate that lobeline does not act as a nicotinic agonist but alters presynaptic dopamine (DA) storage by potently inhibiting DA uptake into synaptic vesicles. Recently, d-amphetamine has been reported to act at the level of the synaptic vesicle to alter presynaptic function. The present in vitro studies further elucidate the mechanism of lobeline's action and compare its effects with those of d-amphetamine. [3H]Dihydrotetrabenazine ([3H]DTBZ), used routinely to probe a high-affinity binding site on the vesicular monoamine transporter (VMAT2), bound to vesicle membranes from rat striatum with a KD of 1.67 nM and Bmax of 8.68 pmol/mg of protein. Lobeline inhibited [3H]DTBZ binding with an IC50 of 0.90 microM, consistent with its previously reported IC50 of 0.88 microM for inhibition of [3H]DA uptake into vesicles. These results suggest that lobeline specifically interacts with DTBZ sites on VMAT2 to inhibit DA uptake into synaptic vesicles. Interestingly, d-amphetamine inhibited [3H]DTBZ binding to vesicle membranes with an IC50 of 39.4 microM, a concentration 20 times greater than reported for inhibition of VMAT2 function, suggesting that d-amphetamine interacts with a different site than lobeline on VMAT2 to inhibit monoamine uptake. Kinetic analysis of [3H]DA release from [3H]DA-preloaded synaptic vesicles in the absence of drug revealed a t1/2 of 2.12 min. Lobeline and d-amphetamine evoked [3H]DA release with EC50 values of 25.3 and 2.22 microM, respectively. At a concentration 10 times the EC50, lobeline and d-amphetamine significantly decreased the t1/2 of [3H]DA release to 1.58 and 1.48 min, respectively. Thus, in contrast to d-amphetamine, which is equipotent in inhibiting DA uptake and promoting release from the synaptic vesicles, lobeline more potently (28-fold) inhibits DA uptake (via an interaction with the DTBZ site on VMAT2) than it evokes DA release to redistribute presynaptic DA storage.

Tozawa F, Dobashi I, Horiba N, Sakai Y, Sakai K, Suda T. Saireito (a Chinese herbal drug) decreases inhibitory effect of prednisolone and accelerates the recovery of rat hypothalamic-pituitary-adrenal axis. Endocr J 1998;45(1):69-74.
Saireito, a saiko agent (a Chinese herbal drug), increases the synthesis and secretion of ACTH by stimulating hypothalamic CRH release. In the present study, we examined the effect of food containing saireito (1.5%) on the recovery of the hypothalamic-pituitary-adrenal axis after treating male rats with prednisolone (PSL, 200 microM) in drinking water for 14 days. Saireito was administered during and after PSL administration. The rats were decapitated at various times after PSL administration. Tail-pinch stress had been applied to some rats. The plasma ACTH response to tail-pinch stress in the PSL + saireito group recovered to the control level on day 1, but that in the group given PSL alone recovered on day 3. The ACTH level in the anterior pituitary and the CRH level in the median eminence of the PSL + saireito group returned to the control level on day 3, and that in the group given PSL alone returned to it on day 5. These results indicate that the administration of saireito reduces the negative feedback effect of PSL on the hypothalamus and pituitary and accelerates the recovery of the hypothalamic CRH and pituitary ACTH level after glucocorticoid treatment.

Turi M, Turi E, Koljalg S, Mikelsaar M. Influence of aqueous extracts of medicinal plants on surface hydrophobicity of Escherichia coli strains of different origin. APMIS 1997;105(12):956-62.
The adhesion of microbes on host cells is of decisive importance in the development of Gram-negative microbe-induced infections and can be influenced by the surface hydrophobicity of the microbial cell. The hydrophobicity of 155 Escherichia coli strains of different origin was determined by the salt aggregation test (SAT). Among the strains isolated from faecal samples of healthy persons only 16.7% showed aggregative properties, whereas among the strains isolated from the urine of patients with pyelonephritis and the faecal samples of calves and pigs with diarrhoea some 40.0%-60.0% were aggregative. The influence of aqueous extracts prepared from bearberry leaves, St. John's wort herbs, wild camomile and marigold flowers on hydrophobicity of 40 E. coli and 20 Acinetobacter baumannii strains was investigated. The decoctions of bearberry and St. John's wort increased remarkably the hydrophobicity of both microbial species. The infusions of wild camomile and marigold completely blocked the aggregative properties of the investigated strains. Bactericidal action was relatively low in the case of bearberry and St. John's wort and completely lacking in the case of wild camomile and marigold. Thus, one of the probable and potentially important action mechanisms of the four medicinal plants studied is their ability to influence the surface characteristics of the microbial cells and thereby their putative virulence properties.

Uebelhack R, Franke L, Schewe HJ. Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava). Pharmacopsychiatry 1998;31(5):187-92.
Kava-kava, a psychoactive beverage, induces relaxation, improves social interaction, promotes sleep and plays an important role in the sociocultural life in the islands of the South Pacific. On the other hand, standardized extracts of kava-kava roots are used for the therapy of anxiety, tension and restlessness. Kava pyrones, the major constituents of kava kava, are generally considered to be responsible for the pharmacological activity in humans and animals. To obtain more information on the mechanisms by which kava-kava exerts psychotropic properties we investigated the in vitro effects of kava-kava extract and pure synthetic kava pyrones on human platelet MAO-B, in comparison to amitriptyline, imipramine and brofaromine. Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC50 24 microM) and disrupted platelet homogenates (IC50 1.2 microM). Structural differences of kava pyrones resulted in a different potency of MAO-B inhibition. The order of potency was desmethoxyyangonin > (+/-)-methysticin > yangonin > (+/-)-dihydromethysticin > (+/-)- dihydrokavain > (+/-)-kavain. The two most potent kava pyrones, desmethoxyyangonin and (+/-)-methysticin displayed a competetive inhibition pattern with mean Ki 0.28 microM and 1.14 microM respectively. The inhibition of MAO-B by kava pyrone-enriched extracts might be an important mechanism for their psychotropic activity.

Vadiraja BB, Gaikwad NW, Madyastha KM. Hepatoprotective effect of C-phycocyanin: protection for carbon tetrachloride and R-(+)-pulegone-mediated hepatotoxicty in rats. Biochem Biophys Res Commun 19998;249(2):428-31.
Effect of C-phycocyanin (from Spirulina platensis) pretreatment on carbontetrachloride and R-(+)-pulegone-induced hepatotoxicity in rats was studied. Intraperitoneal (i.p.) administration (200 mg/kg) of a single dose of phycocyanin to rats, one or three hours prior to R-(+)-pulegone (250 mg/kg) or carbontetrachloride (0.6 ml/kg) challenge, significantly reduced the hepatotoxicity caused by these chemicals. For instance, serum glutamate pyruvate transaminase (SGPT) activity was almost equal to control values. The losses of microsomal cytochrome P450, glucose-6-phosphatase and aminopyrine-N-demethylase were significantly reduced, suggesting that phycocyanin provides protection to liver enzymes. It was noticed that the level of menthofuran, the proximate toxin of R-(+)-pulegone was nearly 70% more in the urine samples collected from rats treated with R-(+)-pulegone alone than rats treated with the combination of phycocyanin and R-(+)-pulegone. The possible mechanism involved in the hepatoprotection is discussed. Copyright 1998 Academic Press.

Veronesi B, Oortgiesen M, Carter JD, Devlin RB. Particulate matter initiates inflammatory cytokine release by activation of capsaicin and acid receptors in a human bronchial epithelial cell line. Toxicol Appl Pharmacol 1999;154(1):106-15.
Recent experiments have shown that human bronchial epithelial cells (i.e., BEAS-2B) release pro-inflammatory cytokines (i.e., IL-6 and TNFalpha) in a receptor-mediated fashion in response to the neuropeptides, substance P (SP), calcitonin gene-related protein (CGRP), and the prototype botanical irritant capsaicin. In the present experiments, we examined the relevance of these receptors to particulate matter (PM)-associated cellular inflammation. BEAS-2B cells, exposed to residual oil fly ash particles (ROFA), responded with an immediate (<30 s) increase in intracellular calcium levels ([Ca2+]i), increases of key inflammatory cytokine transcripts (i.e., IL-6, IL-8, TNFalpha) within 2 h exposure, and subsequent release of IL-6 and IL-8 cytokine protein after 4 h exposure. Pretreatment of BEAS-2B cells with pharmacological antagonists selective for the SP or CGRP receptors reduced the ROFA-stimulated IL-6 cytokine production by approximately 25 and 50%, respectively. However, pretreatment of these cells with capsazepine (CPZ), an antagonist for capsaicin (i.e., vanilloid) receptors, inhibited the immediate increases in [Ca2+]i, diminished transcript (i.e., IL-6, IL-8, TNFalpha) levels and reduced IL-6 cytokine release to control levels. BEAS-2B cells exposed to ROFA in calcium-free media failed to demonstrate increases of [Ca2+]i and showed reduced levels of cytokine transcript (i.e., IL-6, IL-8, TNFalpha) and IL-6 release, suggesting that ROFA-stimulated cytokine formation was partially dependent on extracellular calcium sources. A final set of experiments compared the inflammatory properties of the soluble and acidic insoluble components of ROFA. BEAS-2B cells, exposed to ROFA or ROFA that had been filtered through a 0.2-micrometer pore filter, produced equivocal IL-6. BEAS-2B cells exposed to pH 5.0 media for 15 min released moderate amounts of IL-6, 4 h later. This cytokine release could be blocked by amiloride, a pH receptor antagonist, but not by CPZ. BEAS-2B cells, pretreated with amiloride before ROFA exposure, showed a partial (approximately 25%) reduction of IL-6. Together, these data indicate that the acidic, soluble components of ROFA initiate cytokine release in BEAS-2B cells through activation of both capsaicin- and pH-sensitive irritant receptors. Copyright 1999 Academic Press.

Wang F, Yang LC, Liu M, Cheng YL, Jia HM. [Primary study on antagonizing effects of anti-snake venom Chinese herbs on endothelin-1 and sarafotoxin 6b]. Zhongguo Zhongyao Zazhi 1997;22(10):620-2. (Chi)
IPA COPYRIGHT: ASHP To investigate the pharmacologic effects of Chinese herbs used as anti-snake venom, oral extracts from 5 herbs were evaluated for effects on endothelin-1 and sarafotoxin 6b. All 5 herbs demonstrated acute death reduction caused by endothelin-1 and sarafotoxin 6b.

Wang YQ, Bai LJ, He XW. [Study of scavenging action of Shengmaiyin decoction on hydroxyl radical]. Zhongguo Zhongyao Zazhi 1998;23(1):45-7. (Chi)
IPA COPYRIGHT: ASHP The scavenging action of Shengmaiyin decoction and its individual ingredients, Radix ginseng, R. ophiopogonis, and Fructus schisandrae was investigated. The decoction was better for antioxidation than single ingredients.

Wenisch C, Parschalk B, Zedwitz-Liebenstein K, Wernsdorfer W, Graninger W. The effect of artemisinin on granulocyte function assessed by flow cytometry. J Antimicrob Chemother 1997;39(1):99-101.
The effect of dihydroartemisinin, artemisinin and artesunate (0.1, 0.5, 5 and 50 mg/L) on phagocytic function and release of reactive oxygen products by neutrophils was studied by flow cytometry. Incubation with dihydroartemisinin, artemisinin and artemether resulted in a decreased capacity to phagocytose Escherichia coli (0.1-50 mg/L: 62-40%, 66-32% and 59-47% of the control values, respectively; P < 0.001 for all). Conversely, the derivatives enhanced the intracellular generation of reactive oxygen intermediates (0.1-50 mg/L: 146-140%, 174-197% and 188-136% of the control values, respectively; P < 0.001 for all). Artemisia derivatives enhance the reactive oxygen response of neutrophils but depress their phagocytic ability at therapeutic blood levels.

Xu J, Xie J, Feng P, Su Z. Oxygen transfer characteristics in the compact callus aggregates of Rhodiola sachalinensis. Chin J Biotechnol 1998;14(2):99-107.
The effective diffusivity of oxygen in compact callus aggregates (CCA) of Rhodiola sachalinensis was extremely small, varying from 0.34 x 10(-11) to 5.4 x 10(-9) m2/s and increasing with particle diameter. The calculated results indicated that severe oxygen limitations occurred in the CCA aggregates. However, the direct determination of the viability of the cells demonstrated that the CCA aggregates contained a high fraction of viable cells. It was suggested that the tissue differentiation or plasmodesmata within the CCA aggregates may provide capillaries for improving transport of oxygen and other nutrients.

Yin MC, Cheng WS. Inhibition of Aspergillus niger and Aspergillus flavus by some herbs and spices. J Food Protect 1998;61(1):123-5.
BIOSIS COPYRIGHT: BIOL ABS. The inhibitory effect of water-soluble extracts of garlic bulbs, green garlic, green onions, hot peppers, ginger, Chinese parsley, and basil on the growth of Aspergillus niger and Aspergillus flavus was examined. Garlic bulbs, green garlic, and green onions showed an inhibitory effect against these two fungi. The influence of heat, acid, and salt upon the inhibitory effect of these three herbs was further studied. Increasing the temperature from 60 to 100~C resulted in a significant (P < 0.05) decrease in the inhibitory effect of garlic bulbs against the fungi tested. Green garlic and green onion lost their antifungal activity against A. niger after being treated at 80 and 60~C, respectively. For A. flavus, the inhibitory effect of green garlic declined significantly (P < 0.05) with an increase in temperature. However, the antifungal activity of green onions against A. flavus was heat stable. For both fungi tested in this study, the antifungal activity of these spice plants was not affected by acid treatments at pH values 2, 4, or 6, or salt by treatments at concentrations of 0.1, 0.2, 0.3, and 0.4 M (P > 0.05).

Yokozawa T, Dong E, Oura H, Nonaka G, Nishioka I. Magnesium lithospermate B ameliorates cisplatin-induced injury in cultured renal epithelial cells. Exp Toxicol Pathol 1997;49(5):343-6.
A study was conducted to clarify whether magnesium lithospermate B ameliorates cisplatin-induced renal injury in terms of lactate dehydrogenase and malondialdehyde leakage from LLC-PK1 cells in culture. Magnesium lithospermate B was shown to suppress the cytotoxicity of cisplatin, the suppressive effect increasing with the dose of magnesium lithospermate B.

Yoshikawa M, Murakami T, Ueno T, Yashiro K, Hirokawa N, Murakami N, Yamahara J, Matsuda H, Saijoh R, Tanaka O. Bioactive saponins and glycosides. VIII. Notoginseng (1): new dammarane-type triterpene oligoglycosides, notoginsenosides-A, -B, -C, and -D, from the dried root of Panax notoginseng (Burk.) F.H. Chen. Chem Pharm Bull (Tokyo) 1997;45(6):1039-45.
The glycosidic fraction from the dried roots of Panax notoginseng (Burk.) F.H. Chen was found to show protective effect on liver injury induced by D-galactosamine and lipopolysaccharide. From the glycosidic fraction with hepatoprotective effect, nine new dammarane-type triterpene oligoglycosides, notoginsenosides-A, -B, -C, -D, -E, -G, -H, -I, and -J and an acetylenic fatty acid glycoside, notoginsenic acid beta-sophoroside, were isolated together with fourteen known dammarane-type triterpene oligoglycosides. The structures of notoginsenosides-A, -B, -C and -D were determined on the basis of chemical and physicochemical evidence, which included the chemical correlation with ginsenoside-Rb1 using photosensitized oxygenation, as follows: notoginsenoside A; 3-O-[beta-D-glucopyranosyl (1-->2)-beta-D-glucopyranosyl]-20-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] 3 beta, 12 beta,20(S),25-tetrahydroxydammar -23-ene; B; 3-O-[beta-D-glucopyranosyl (1-->2)-beta-D-glucopyranosyl]-20-O-[beta-D-glucopyranosyl (1-->6)-beta-D- glucopyranosyl] 3 beta, 12 beta,20(S)-trihydroxydammar-25-en-24-one, C; 3-O-[beta-D-glucopyranosyl (1-->2)-beta-D-glucopyranosyl]-20-O-[beta-D -glucopyranosyl (1-->6)-beta-D-glucopyranosyl] 3 beta,12 beta,20(S)- trihydroxy-24 zeta-hydroperoxydammar-25-ene, and D; 3-O-[beta-D-xylopyranosyl (1-->2)-beta-D-glucopyranosyl (1-->2)-beta-D-glucopyranosyl]-20-O-[beta-D-xylopyranosyl (1-->6)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl]20(S)-protopanaxadiol, respectively.

Yoshikawa M, Murakami T, Yashiro K, Yamahara J, Matsuda H, Saijoh R, Tanaka O. Bioactive saponins and glycosides. XI. Structures of new dammarane-type triterpene oligoglycosides, quinquenosides I, II, III, IV, and V, from American ginseng, the roots of Panax quinquefolium L. Chem Pharm Bull (Tokyo) 1998;46(4):647-54.
The methanolic extract and 1-butanol-soluble fraction of American ginseng, the roots of Panax quinquefolium L., were found to exhibit a protective effect on liver injury induced by D-galactosamine and lipopolysaccharide. Five new dammarane-type triterpene oligoglycosides called quinquenosides I, II, III, IV, and V were isolated together with fourteen known dammarane-type triterpene oligoglycosides such as chikusetsusaponin IVa, pseudo-ginsenoside-RC1, malonyl-ginsenoside-Rb1, and notoginsenosides-A,-C, and -K from the 1-butanol-soluble fraction. From the ethyl acetate-soluble fraction, four known acetylenic compounds and 6'-O-acetyl ginsenoside-Rg1 were isolated. The structures of quinquenosides I, II, III, IV, and V were determined on the basis of chemical and physicochemical evidence as 3-O-[6-O-(E)-2-butenoyl-beta-D-glucopyranosyl(1-->2)-beta-D- glucopyranosyl]-20-O-(beta-D-glucopyranosyl) 20(S)-protopanaxadiol (quinquenoside I), 3-O-[6-O-(E)-2-octenoyl-beta-D- glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-[beta-D-glucopy- ranosyl (1-->6)-beta-D-glucopyranosyl] 20(S)-protopanaxadiol (quinquenoside II), 3-O-[beta-D-glucopyranosyl (1-->2)-6-O-acetyl-beta-D-glucopyranosyl]-20-O-(beta-D-glucopyran- osyl) 20(S)-protopanaxadiol (quinquenoside III), 3-O-[beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-bet- a-D- glucopyranosyl(1-->6)-beta-D-glucopyranosyl]-3 beta, 7 beta, 20(S)-trihydroxydammar-5,24-diene (quinquenoside IV), and 3-O-[beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-[al- pha-D- glucopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopy- ranosyl ] 20(S)-protopanaxadiol (quinquenoside V).

Yotsumoto H, Yanagita T, Yamamoto K, Ogawa Y, Cha JY, Mori Y. Inhibitory effects of oren-gedoku-to and its components on cholesteryl ester synthesis in cultured human hepatocyte HepG2 cells: evidence from the cultured HepG2 cells and in vitro assay of ACAT. Planta Med 1997;63(2):141-5.
The pharmacological effects of Oren-gedoku-to (OGT), a Japanese-Chinese traditional herbal medicinal mixture on lipid biosynthesis were investigated in cultured human hepatocyte HepG2 cells. The addition of OGT (0.5 and 4.2 mg/ml), which had no effect on cell proliferation and cellular protein content, caused a marked decrease in the cellular cholesterol content, particularly cholesteryl ester content following 24 h incubation. The incorporation of 14C-oleate into cellular cholesteryl ester fraction was also reduced remarkably during incubation for 6 and 24 h. The effects of OGT, its components and its main active chemicals on acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity were studied in vitro to explore the mechanism by which OGT inhibits cholesteryl ester formation. The data confirmed that OGT, in a dose-dependent manner, and its components (Scutellaria baicalensis, Coptis japonica, Gardenia jasminoides and Phellodendron amurense) remarkably inhibit ACAT activity. Among the main active chemicals of OGT, baicalein, a kind of flavonoid, decreased ACAT activity in a dose-dependent fashion from the level of 10(-6)M. These results strongly suggest that OGT reduces the cholesteryl ester formation in human hepatocytes by inhibiting ACAT, and that baicalein may, in part, be responsible for ACAT inhibition.

Zava DT, Blen M, Duwe G. Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture. Environ Health Perspect 1997;105(Suppl 3):637-45.
We investigated the estrogenic activity of various environmental pollutants (xenobiotics), in particular the xenoestrogen o,p-DDT, and compared their effects with those of endogenous estrogens, phytoestrogens, and mycoestrogens on estrogen receptor binding capacity, induction of estrogen end products, and activation of cell proliferation in estrogen-sensitive human breast cancer cells in monolayer culture. We also quantified the levels of phytoestrogens in extracts of some common foods, herbs, and spices and in human saliva following consumption of a high phytoestrogen food source (soy milk) to compare phytoestrogen abundance and bioavailability relative to the reported xenoestrogen burden in humans. Results show that natural endogenous estrogens, phytoestrogens, mycoestrogens, and xenoestrogens bind estrogen receptor (ER) in intact cells, but demonstrate marked differences in their ability to induce end products of estrogen action and to regulate cell proliferation. All of the different classes of estrogens stimulated cell proliferation at concentrations that half-saturated ER, but only some classes were able to induce estrogen-regulated end products. Genistein, a common phytoestrogen found in soy foods, differed from the xenoestrogen DDT in its effects on cell proliferation and ability to induce estrogen-regulated end products. Moreover, we found that many of the foods, herbs, and spices commonly consumed by humans contain significant amounts of phytoestrogens, and consumption of soy milk, a phytoestrogen-rich food, markedly increases the levels of phytoestrogens in saliva. In conclusion, our in vitro results predict that a diet high in phytoestrogens would significantly reduce the binding of weak xenoestrogens to ER in target tissues in vivo.

Zava DT, Dollbaum CM, Blen M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 1998;217(3):369-78.
In this study we report on the content and bioactivity of plant (phyto) estrogens and progestins in various foods, herbs, and spices, before and after human consumption. Over 150 herbs traditionally used by herbalists for treating a variety of health problems were extracted and tested for their relative capacity to compete with estradiol and progesterone binding to intracellular receptors for progesterone (PR) and estradiol (ER) in intact human breast cancer cells. The six highest ER-binding herbs that are commonly consumed were soy, licorice, red clover, thyme, tumeric, hops, and verbena. The six highest PR-binding herbs and spices commonly consumed were oregano, verbena, tumeric, thyme, red clover and damiana. Some of the herbs and spices found to contain high phytoestrogens and phytoprogestins were further tested for bioactivity based on their ability to regulate cell growth rate in ER (+) and ER (-) breast cancer cell lines and to induce or inhibit the synthesis of alkaline phosphatase, an end product of progesterone action, in PR (+) cells. In general, we found that ER-binding herbal extracts were agonists, much like estradiol, whereas PR-binding extracts, were neutral or antagonists. The bioavailability of phytoestrogens and phytoprogestins in vivo were studied by quantitating the ER-binding and PR-binding capacity of saliva following consumption of soy milk, exogenous progesterone, medroxyprogesterone acetate, or wild mexican yam products containing diosgenin. Soy milk caused a dramatic increase in saliva ER-binding components without a concomitant rise in estradiol. Consumption of PR-binding herbs increased the progestin activity of saliva, but there were marked differences in bioactivity. In summary, we have demonstrated that many of the commonly consumed foods, herbs, and spices contain phytoestrogens and phytoprogestins that act as agonists and antagonists in vivo.

Zhao C, Shichi H. Prevention of acetaminophen-induced cataract by a combination of diallyl disulfide and N-acetylcysteine. J Ocul Pharmacol Ther 1998;14(4):345-55.
Injection of acetaminophen (APAP) (350 mg/kg body weight) into C57BL/6 mice in which cytochrome P450 (CYP) 1A1/1A2 had been induced produced acute cataract and other ocular tissue damage. Treatment of APAP-injected mice with one of the major organosulfides in garlic oil, diallyl disulfide (DADS) (200 mg/kg body weight), prevented cataract development and prolonged survival time. N-acetyl L-cysteine (NAC) (500 mg/kg body weight), a prodrug that stimulates glutathione synthesis, also prolonged survival time but was effective only weakly to prevent cataract formation. A combination of DADS and NAC completely prevented cataractogenesis, and all of the treated animals survived APAP toxicity. Neither DADS nor NAC inhibited CYP 1A1/1A2 induction as determined by their effect on the induction of hepatic microsomal ethoxyresorufin O-dealkylase (ERD) activity. However, in the in vitro enzyme assay, DADS, but not NAC, was a potent inhibitor of ERD activity (IC50 = 3.5 mM). Treatment with DADS or NAC slowed but did not stop the decrease of hepatic glutathione (GSH) content. At 4 hours after APAP injection, hepatic GSH began to increase only when DADS and NAC were administered together. These results suggest that the protective effect of DADS is due to its inhibition of biotransformation of APAP to the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI) by CYP 1A1/1A2 enzymes and that NAC provides protection by increasing cellular cysteine level and GSH synthesis, thus facilitating detoxification of NAPQI by glutathione conjugation. Assay of plasma glutamate-pyruvate transaminase activity, an indicator of liver necrosis, showed that treatment with DADS and NAC together effectively protected the liver. Therefore, the decrease of GSH as much as 30% of normal concentration, by itself, is not responsible for liver damage. The primary cause of hepatic necrosis is rapid accumulation of NAPQI.

Zhu M, Chan KW, Ng LS, Chang Q, Chang S, Li RC. Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats. J Pharm Pharmacol 1999;51(2):175-80.
We evaluated the significance of a reported clinical case of drug-drug interaction between ginseng and warfarin using a robust pharmacokinetic/pharmacodynamic approach in a rat model. The influence of ginseng on the pharmacokinetics and pharmacodynamics of oral warfarin after a single dose (2 mg kg(-1)) and at steady state (0.2 mg kg(-1) daily x 6 days) was studied in male Sprague-Dawley rats. Prothrombin time was employed as a pharmacodynamic index. Warfarin plasma concentration and vitamin K content in the ginseng extract were assessed by validated HPLC assays. The pharmacokinetics of warfarin after a single dose were not altered in the presence of ginseng; peak plasma concentration (control 7.8+/-0.5; ginseng 7.3+/-2.5 microg mL(-1)), time to peak (control 2.6+/-1.0; ginseng 3.1+/-1.1 h), elimination half-life (control 14.3+/-5.8; ginseng 10.6+/-3.1 h), and oral clearance (control 17.5+/-3.3; ginseng 20.2+/-5.5 mL h(-1)) were not significantly different (P>0.05). Similarly, alterations in the pharmacokinetics of warfarin were not detected under the multiple dosing paradigm. Under both dosing conditions, ginseng also showed no significant impact on the pharmacodynamics of warfarin as assessed by the area under the prothrombin time vs time curve (multiple dosing; control 3776+/-619, ginseng 3830+/-362 sh) and maximum prothrombin time (control 57.2+/-11.8, ginseng 63.3+/-9.1 s). Furthermore, the content of vitamin K was undetectable in the ginseng decoction. In conclusion, current data obtained in the rat showed no significant impact of ginseng on the pharmacokinetics/pharmacodynamics of warfarin when they are concomitantly administered.

. Piper methysticum (kava kava). Altern Med Rev 1998;3(6):458-60.
Piper methysticum (kava kava) is a plant native to the Pacific Island region, and has been used ceremonial for thousands of years. The active ingredients are a group of substances know as kava lactones (AKA kava pyrones). Four lactones in kava have been found to have significant analgesic and anesthetic effects via non-opiate pathways. Kava's most popular application is as a natural anxiolytic, comparing favorably in several studies to a number prescription medications, including benzodiazepines. CNS effects seem to be mediated by several mechanisms. Studies have been conflicting regarding its GABA-receptor-binding capacity, although this has been found to occur in some studies. In vitro kava has been found to block norepinephrine uptake. It also has some anti-convulsant capabilities, which appear to be mediated by Na+ channel receptor sites. The therapeutic dosage is in the range of 50-70 mg kava lactones three times daily. The most common side effect, usually seen only with long-term, heavy usage of the herb, is a scaly skin rash called "kava dermopathy." It has also been know to potentiate other medications such as barbiturates and Xanax.

. [To diagnose and treat sinusitis. 8th Congress of the Society for Phytotherapy. Symposium: "Phytotherapy in Sinusitis". Wurzburg 27 November 1997]. Dtsch Med Wochenschr 1998;123(10 Suppl):1-4. (Ger)

Abe S, Tansho S, Ishibashi H, Inagaki N, Komatsu Y, Yamaguchi H. Protective effect of oral administration of a traditional medicine, Juzen-Taiho-To, and its components on lethal Candida albicans infection in immunosuppressed mice. Immunopharmacol Immunotoxicol 1998;20(3):421-31.
Protective effects of a kampo medicine, Juzen-taiho-to (TJ-48) and its herbal components against experimental candidiasis in cyclophosphamide-induced immunosuppressive mice were investigated. ICR mice were immunosuppressed by intraperitoneal treatment with cyclophosphamide (day-4) and were orally given TJ-48 or one of its 10 herbal components for 4 consecutive days (day-4--1). They were then challenged intravenously with a lethal dose of Candida albicans (day 0). An oral dose of 1 g/kg/day of TJ-48 prolonged their life span. A similar protective effect was obtained by treatment with its component drugs Ginseng radix, Glycyrrhizae radix, Atractylodis lancea rhizoma or Cnidii rhizoma. These herbal components were suggested to have a main role in the protective effect of Juzen-taiho-to against Candida infection.

Agrawal AK, Tripathi DM, Sahai R, Gupta N, Saxena KC, et al. Management of giardiasis by the herbal drug Pippali Rasayana: clinical study. J Ethnopharmacol 1997;56(3):233-6.
IPA COPYRIGHT: ASHP The effectiveness of Pippali Rasayana, an Indian Ayurvedic drug prepared from Palash (Butea monosperma) and Pippali (Piper longum), administered at an oral dose of 1 g 3 times daily for 15 days to 25 patients and 25 placebo controls suffering from giardiasis is reported. After 15 days of treatment there was a complete disappearance of trophozoites and cysts from stools of 23 of the patients. General signs and symptoms of ill health and abdominal discomfort, presence of mucus, pus cells, and RBCs were significantly reduced. There was a marked improvement in the clinical and hematological profile of the patients. Spontaneous recovery in 20% of cases was recorded in placebo controls.

Ahmad H, Tijerina MT, Tobola AS. Preferential overexpression of a class MU glutathione S-transferase subunit in mouse liver by myristicin. Biochem Biophys Res Commun 1997;236(3):825-8.
The present studies were undertaken to elucidate the mechanism of induction of glutathione S-transferase (GST) in mouse liver by myristicin, an active constituent of parsley leaf. A/J albino mice, given 5 to 50 mg doses of myristicin, showed 4- to 14-fold increase in liver GST specific activity over the control. GST purified from equal amounts of control and myristicin-treated livers indicated a marked increase in the GST activity. A relatively higher increase in GST activity towards 2,4-dichloronitrobenzene and a profound increase in the levels of GST mu on Western blot analysis of the myristicin-treated mouse liver suggest a preferential induction of GST mu. Results of the study also indicate that out of the two mu class GST subunits (Mr. 26,500 and Mr. 25,000) expressed in liver only one (Mr. 26,500) is significantly elevated. Myristicin treatment caused a slight change in the GST pi levels while the levels of GST alpha showed a modest increase. These results suggest that myristicin could be an effective chemopreventive agent, particularly for carcinogens that are detoxified by the mu class GST.

Ahn YO. Diet and stomach cancer in Korea. Intl J Cancer Suppl 1997;(10):7-9.
BIOSIS COPYRIGHT: BIOL ABS. Stomach cancer is the most prevalent malignant neoplasm in Korea. As of 1991-1992 in Seoul, the cumulative rates reported for the age span 0-74 were 7.6% in males and 3.1% in females. A recent case-control study reported that several food items and cooking methods are associated with increased or decreased risk of stomach cancer among Koreans. An increased risk of stomach cancer was noted among people who frequently consume broiled meats and fishes, salted side dishes (salted/fermented fish products) and salty stewed foods, such as soybean paste thick stew. Frequent consumption of mung bean pancake, tofu, cabbage, spinach and sesame oil decreased the risk. Analysis by cooking method showed that risk of stomach cancer from the same foods varied with preparation. For meat and fish, pan frying was associated with decreased risk, whereas stewing or broiling was associated with increased risk. Pickled vegetables increased the risk, whereas fresh vegetables did not. In a recent cohort study in Seoul, green vegetables and soybean foods were associated with a decreased risk of stomach cancer. Case-control and cohort studies have reported that ginseng intake decreased the risk of gastric cancer.

Aida Y, Kasama T, Takeuchi N, Chiba M, Tobinaga S. Pharmacological activities of khellactones, compounds isolated from Peucedanum japonicum THUNB. and Peucedanum praeruptorium DUNN. Methods Find Exp Clin Pharmacol 1998;20(4):343-51.
The spasmolytic and antiallergic effects of AA and BB, compounds isolated from Peucedanum japonicum THUNB. (P. japonicum THUNB.) and Peucedanum praeruptorium DUNN. (P. praeruptorium DUNN.), were investigated in isolated smooth muscle and rat PCA. AA and BB showed noncompetitive antagonistic effects on Ach- and histamine-induced contraction in the isolated guinea pig ileum. Both AA and BB at 10(-6) g/ml caused a slight shift to the right of the dose-response curve for Ca2+ in isolated guinea pig ileum, and a concentration up to 3 x 10(-6) g/ml displayed noncompetitive antagonistic effects. The Ba2+ (3 x 10(-4) g/ml)-induced contraction in ileum and the histamine (10(-3) g/ml)-induced contraction in trachea were obtained to relaxation by AA and BB in a concentration-dependent fashion. AA and BB showed noncompetitive antagonist action on serotonin-induced contraction of the rat uterus excised 24-48 h after subcutaneous injection of female rats with estradiol. But, AA and BB were found to have hardly any inhibitory effect on rabbit thoracic aorta contractions induced by epinephrine (3 x 10(-6) g/ml). When the effect of oral administration of 40 mg/kg dose of BB was tested on the rat homologous PCA using anti-egg albumin mouse serum dilutions (1:100, 1:250, 1:500 and 1:750), it inhibited the 1:750 serum reaction 42.6%, but the inhibition rates for the other dilutions were 12-20%. Thus, based on the results of testing AA and BB, compounds isolated from P. japonicum THUNB. and P. praeruptorium DUNN. were confirmed to possess a spasmolytic effect on different types of smooth muscle and a mild antiallergic effect. These findings are of interest in regard to the medical uses of P. japonicum THUNB. and P. praeruptorium DUNN. as a herbal drug for bronchial asthma, spasmolytic effect, etc.

Akah PA, Gamaniel KS, Samson A, Wambebe CO. Evaluation of Nigerian traditional medicine: effects of Gakani, a herbal anti-asthmatic drug. J Ethnopharmacol 1997;55(2):87-92.
The anti-asthmatic potential of Gakani, a popular herbal drug in Nigeria was investigated. The LD50 values of the freeze-dried aqueous extract in mice and rats were 20.9 +/- 2.4 mg/kg and 18.6 +/- 4 mg/kg, respectively. The extract unsurmountably blocked the effects of histamine and isoprenaline on the guinea pig tracheaL chain. It produced initial dose-related contractions of the isolated guinea pig ileum and rat stomach strip, which was followed by persistent autoinhibition and inhibition of histamine- and 5-hydroxytryptamine (5-HT)-induced responses of the two preparations, respectively. The extract had good anti-inflammatory effect in rats, causing a dose-related inhibition of the increase in the paw circumference (acute inflammation) induced by subplantar injection of fresh egg albumin. These results highlight the anti-asthmatic and toxic potential of this preparation and the need for a systemic approach in the study of traditional medicines.

Akah PA, Nwambie AI, Gamaniel KS, Wambebe C. Experimental study of the anticonvulsant plants used for treatment of infantile convulsion in Nigeria. Brain Res Bull 1997;44(5):611-3.
In Nigeria, convulsion, especially in children, is managed by traditional healers employing plant decoctions. A number of herbs are used for this purpose. We have carried out some preliminary studies on some of these traditional anticonvulsant plants. The experimental models were pentylenetetrazole- and electroshock-induced convulsions in mice. The acute toxicity (LD50) and the median effective (ED50) doses of the extracts of these plants were determined. Most of these plants exhibited potent anticonvulsant activity. The average onset of convulsion was delayed, while the average duration of convulsion was significantly reduced. Most of the animals showed signs of central nervous system depression. The results indicate that these plants possess anticonvulsant property, and this activity may be linked to their ability to depress the central nervous system.

Al-Khalil S, Alkofahi A, El-Eisawi D, Al-Shibib A. Transtorine, a new quinoline alkaloid from Ephedra transitoria. J Nat Prod 1998;61(2):262-3.
Transtorine (1), a new quinoline alkaloid, isolated from the aerial part of Ephedra transitoria by column chromatography, was identified as 4-quinolone-2-carboxylic acid. The structure was determined by spectroscopic methods. Transtorine exhibited growth inhibitory activity against the common bacteria, Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.

Alali FQ, Zhang Y, Rogers L, Mclaughlin JL. (2,4-cis and trans)-gigantecinone and 4-deoxygigantecin, bioactive nonadjacent bis-tetrahydrofuran annonaceous acetogenins, from Goniothalamus giganteus. J Nat Prod 1997;60(9):929-33.
Two new acetogenins, (2,4-cis and trans)-gigantecinone (1), isolated as a mixture, and 4-deoxygigantecin (2), a known acetogenin whose absolute stereochemistry has not been determined previously, were isolated using activity-directed fractionation, from the bark of Goniothalamus giganteus. A key step in solving their absolute stereochemistries was the preparation of 1,4-diol formaldehyde acetal derivatives (1b and 2a). Using the advanced Mosher ester method and circular dichroism, the absolute stereochemistries of 1 and 2 were revealed and were found to be the same as that of gigantecin (3), which supports a common biogenetic origin. Both 1 and 1b showed potent and selective cytotoxicities against the PC-3 human prostate adenocarcinoma cell line. Against yellow fever mosquito larvae, 1 and 2 were more potent than rotenone in pesticidal activity. Longimicin C and a mixture of (2,4-cis and trans)-isoannonacin were also isolated for the first time from this species.

Alam MI, Gomes A. Adjuvant effects and antiserum action potentiation by a (herbal) compound 2-hydroxy-4-methoxy benzoic acid isolated from the root extract of the Indian medicinal plant 'sarsaparilla' (Hemidesmus indicus R. Br.). Toxicon 1998;36(10):1423-31.
The adjuvant effect and antiserum potentiation of a compound 2-hydroxy-4-methoxy benzoic acid were explored in the present investigation. This compound, isolated and purified from the Indian medicinal plant Hemidesmus indicus R. Br, possessed antisnake venom activity. Rabbits immunized with Vipera russellii venom in the presence and absence of the compound along with Freund's complete adjuvant, produced a precipitating band in immunogel diffusion and immunogel electrophoresis. The venom neutralizing capacity of this antiserum showed positive adjuvant effects as evident by the higher neutralization capacity (lethal and hemorrhage) when compared with the antiserum raised with venom alone. The pure compound potentiated the lethal action neutralization of venom by commercial equine polyvalent snake venom antiserum in experimental models. These observations raised the possibility of the use of chemical antagonists (from herbs) against snake bite, which may provide a better protection in presence of antiserum, especially in the rural parts of India.

Alvarez L, Rios MY, Esquivel C, Chavez MI, Delgado G, Aguilar MI, Villarreal ML, Navarro V. Cytotoxic isoflavans from Eysenhardtia polystachya. J Nat Prod 1998;61(6):767-70.
Two new cytotoxic isoflavans, (3S)-7-hydroxy-2',3',4',5', 8-pentamethoxyisoflavan (1) and (3S)-3',7-dihydroxy-2',4',5', 8-tetramethoxyisoflavan (2), were isolated from the bark and trunks of Eysenhardtia polystachya (Leguminosae), together with the known constituents stigmasterol, isoduartin, cuneatin, 7-hydroxy-2',4', 5'-trimethoxyisoflavone, and 3,4-dimethoxy-8, 9-(methylenedioxy)pterocarpan. The structures of 1 and 2 were elucidated on the basis of spectroscopic methods. The antimicrobial, cytotoxic, and insecticidal potential of some of these compounds were evaluated. The isoflavans 1, 2, and isoduartin (2', 7-dihydroxy-3',4',8-trimethoxyisoflavan) displayed moderate cytotoxic activity against KB cell lines.

Ameri A. Effects of the alkaloids 6-benzoylheteratisine and heteratisine on neuronal activity in rat hippocampal slices. Neuropharmacology 1997;36(8):1039-46.
Alkaloids of different Aconitum species are employed as analgesics in traditional Chinese folk medicine. The present study was designed in order to investigate the effects of the structurally related alkaloids 6-benzoylheteratisine and heteratisine on neuronal activity in rat hippocampus. Experiments were performed as extracellular recordings of stimulus evoked population spikes in rat hippocampal slices. 6-Benzoylheteratisine (0.01-10 microM) inhibited the ortho- and antidromic population spike as well as the field EPSP in a concentration- and frequency-dependent manner. Heteratisine (1-100 microM) was a less potent inhibitor. It exerted a depression of the orthodromic spike, but failed to affect the antidromic population spike. 6-Benzoylheteratisine (10 microM) diminished epileptiform activity induced by bicuculline. In hippocampal neurons, this compound reduced the peak amplitude of the sodium current. There was no effect of heteratisine on the sodium current in concentrations up to 100 microM. It is concluded that the frequency-dependent action of 6-benzoylheteratisine suggests an inhibition of neuronal activity which underlies epileptiform burst discharges. The predominant effect is a suppression of neuronal activity due to a blockade of sodium channels.

Annuk H, Hirmo S, Turi E, Mikelsaar M, Arak E, Wadstrom T. Effect on cell surface hydrophobicity and susceptibility of Helicobacter pylori to medicinal plant extracts. FEMS Microbiol Lett 1999;172(1):41-5.
Effects on aqueous extracts of medicinal plants on ten Helicobacter pylori strains were studied by the salt aggregation test to determine the possibility to modulate their cell surface hydrophobicity and by an agar diffusion assay for detection of antimicrobial activity. It was established that aqueous extracts of bearberry and cowberry leaves enhance cell aggregation of all H. pylori strains tested by the salt aggregation test, and the extract of bearberry possessed a remarkable bacteriostatic activity. Pure tannic acid showed a result similar to that of bearberry and cowberry extracts which contained a large amount of tannins. In contrast, extracts of wild camomile and pineapple-weed, which blocked aggregation of H. pylori, contained small amounts of tannins and did not reveal any antimicrobial activity. Tannic acid seems to be the component of bearberry and cowberry aqueous extracts with the highest activity to decrease cell surface hydrophobicity as well as in antibacterial activity against H. pylori.

Ansar S, Iqbal M, Athar M. Nordihydroguairetic acid is a potent inhibitor of ferric-nitrilotriacetate-mediated hepatic and renal toxicity, and renal tumour promotion, in mice. Carcinogenesis 1999;20(4):599-606.
Ferric-nitrilotriacetate (Fe-NTA) is a known renal carcinogen. In the present study, we report the effect of a potent lignin-derived herbal antioxidant, nordihydroguairetic acid (NDGA), against Fe-NTA-mediated tissue toxicity. Fe-NTA (alone) treatment of mice enhances ornithine decarboxylase activity to 259% in liver and 341% in kidney and increases [3H]thymidine incorporation in DNA to 250% in liver and 324% in kidney compared with the corresponding saline-treated controls. The enhanced ornithine decarboxylase activity and DNA synthesis showed a reduction to 138 and 123%, respectively, in liver at a higher dose of 2 mg NDGA/day/animal whereas in kidney the reduction was to 118 and 102%, respectively, compared with the corresponding saline-treated controls. In the Fe-NTA (alone)-treated group, a 12% renal tumour incidence was recorded whereas, in N-diethylnitrosamine (DEN)-initiated and Fe-NTA-promoted animals, the percentage tumour incidence was increased to 68% as compared with untreated controls. No tumour incidence was recorded in the DEN-initiated, non-promoted group. The administration of NDGA, afforded >80% protection against DEN- and Fe-NTA-mediated renal tissue injury in vivo. Fe-NTA treatment also enhanced hepatic and renal microsomal lipid peroxidation to 170 and 205% of saline-treated controls, respectively, and hydrogen peroxide generation by >2.5-fold in both tissues accompanied by a 51 and 21% decrease in the level of glutathione and 35-48 and 35-50% decrease in the activities of glutathione-metabolizing and antioxidant enzymes in liver and kidney, respectively. These changes were reversed significantly in animals receiving a pre-treatment of NDGA. Our data show that NDGA can abrogate the toxic and tumour-promoting effects of Fe-NTA in liver and kidney of mice and can serve as a potent chemopreventive agent to suppress oxidant-induced tissue injury and tumorigenesis.

Arisawa M, Hayashi K, Nikaido T, Koike K, Sasaki T, et al . Screening of some marine organism extracts for cAMP phosphodiesterase inhibition, cytotoxicity, and antiviral activity against HSV-1. Int J Pharmacogn 1997;35(1):6-11.
IPA COPYRIGHT: ASHP Extracts of 71 samples of 56 kinds of marine products were subjected to an inhibitory test for cyclic AMP (cAMP) phosphodiesterase, and to cytotoxic and antiviral screening tests. Seven extracts of marine products showed significant abilities to inhibit cAMP phosphodiesterase and 5 extracts showed significant cytotoxicity against KB cells at concentrations under 20 mcg/ml. Eight extracts of marine products showed higher therapeutic indexes against herpes simplex virus type 1 (HSV-1).

Awang DV. Parthenocide: demise of a facile theory of feverfew activity. J Herbs Spices Med Plants 1998;5(4):95-8.
IPA COPYRIGHT: ASHP Since the publication of 2 migraine clinical studies in which a dried alcoholic extract of Tanacetum parthenium (L.) (feverfew) containing 0.35% parthenolide demonstrated no activity and dried powdered leaves containing 0.2% parthenolide demonstrated a significant reduction in pain intensity and severity of symptoms, the theory that parthenolide is the active ingredient in T. parthenium is discussed.

Awang DV. Saw palmetto, African prune and stinging nettle for benign prostatic hyperplasia (BPH). Can Pharm J 1997 Nov;130:37-40, 43-44, 62.
IPA COPYRIGHT: ASHP The beneficial effects of saw palmetto (Serenoa repens), African prune (Prunus africana), and stinging nettle (Urtica dioica) for the treatment of benign prostatic hyperplasia (BPH) are discussed.

Batey RG, Bensoussan A, Fan YY, Bollipo S, Hossain MA. Preliminary report of a randomized, double-blind placebo-controlled trial of a Chinese herbal medicine preparation CH-100 in the treatment of chronic hepatitis C. J Gastroenterol Hepatol 1998;13(3):244-7.
The treatment of chronic hepatitis C is relatively unsatisfactory and many patients have turned to unproven alternative medicines to modify the course of their illness. We report a study of a Chinese herbal medicine preparation CH-100 in the management of chronic hepatitis C. Patients with documented chronic hepatitis C were randomly allocated to receive active herbal or placebo tablets (five tablets thrice daily). Patients were followed monthly and evaluated by a Western and a traditional Chinese medical practitioner. Therapy was monitored by measurement of liver function tests, creatinine and full blood count on a monthly basis. Twenty patients in each group were well matched for age, sex, duration of illness, previous interferon therapy and alcohol intake. Active Chinese herbal medication was associated with a significant reduction in alanine aminotransferase (ALT) levels over the 6 month study period (P < 0.03). No patient cleared the virus but four normalized their ALT on treatment. Appropriately prescribed Chinese herbal medicine may have a role in the management of chronic hepatitis C and further controlled studies are indicated.

Batz F. Integrating herbal therapy into practice. Am Drug 1998 May;215:58-65.
IPA COPYRIGHT: ASHP The integration of herbal therapy into pharmacy practice is discussed, including the uses and precautions of commonly used herbs, quality and regulatory issues associated with herbal medicine, examples of herbal adverse reactions, herb-drug interactions, toxic herbs, information sources for herbal medicine, and the pharmacist's role in assisting patients in the safe use of herbs. This article qualifies for 2 hours U.S. CE credit by the ACPE.

Baxter A. Treating depression with St. John's wort. N Z Pharm1998 Jan;18:35.
IPA COPYRIGHT: ASHP The effectiveness and possible mechanism of action of Hypericum perforatum (St. John's wort) for the treatment of depression are discussed.

Benoit-Vical F, Valentin A, Cournac V, Pelissier Y, Mallie M, Bastide JM. In vitro antiplasmodial activity of stem and root extracts of Nauclea latifolia S.M. (Rubiaceae). J Ethnopharmacol 1998;61(3):173-8.
Aqueous extracts from Nauclea latifolia S.M. (Rubiaceae), a plant commonly used in Ivory Coast by traditional healers for the treatment of malaria, were tested on two strains of Plasmodium faliparum: FcB1-Colombia (chloroquine-resistant) and a Nigerian strain (chloroquine-sensitive). The extracts were obtained from stems and roots of the plant in two forms, infusion and decoction, both methods used by most traditional healers. The in vitro activity of N. latifolia extracts on P. falciparum was assessed both visually and by a radioactive method. The visual analysis allowed determination of the time of extract action on the erythrocytic cycle, as well as the parasitic stage of most inhibitory effect. Similar results were obtained applying fresh, frozen or lyophilized extracts. The IC50 values determined were within the range already reported for other antimalarial plants such as Azadirachta indica A. Juss (Meliaceae) or Artemisia annua L. (Asteraceae). Aqueous extracts of N. latifolia inhibited P. falciparum (FcB1 strain) mainly at the end of the erythrocytic cycle (32nd to 48th hour).

Berthold HK, Sudhop T, Von Bergmann K. Effect of a garlic oil preparation on serum lipoproteins and cholesterol metabolism: randomized controlled trial. JAMA 1998 Jun 17;279:1900-2.
IPA COPYRIGHT: ASHP A randomized, double blind, placebo controlled, crossover study evaluating the antilipemic effects and mechanism of an enteric-coated garlic oil (Tegra) preparation was conducted in 25 hypercholesterolemia patients, mean age 58 yr, who received 5 mg of the garlic oil preparation twice daily and a matching placebo each for 12 wk in a crossover fashion with a 4 wk placebo washout between treatment periods. Lipoprotein levels were virtually unchanged at the end of both treatment periods. Cholesterol absorption, cholesterol synthesis, mevalonic acid excretion, and changes in the ratio of lathosterol to cholesterol in the serum were not different during garlic and placebo treatment. It was concluded that garlic therapy for the treatment of hypercholesterolemia cannot be recommended on the basis of this study.

Bhandari U, Sharma JN, Zafar R. The protective action of ethanolic ginger (Zingiber officinale) extract in cholesterol fed rabbits. J Ethnopharmacol 1998;61(2):167-71.
The effects of ethanolic extract of ginger (200 mg/kg, p.o.) were studied in cholesterol fed rabbits. The marked rise in serum and tissue cholesterol, serum triglycerides, serum lipoproteins and phospholipids that followed 10 weeks of cholesterol feeding, was significantly reduced by the ethanolic ginger extract and results were compared with gemfibrozil, a standard orally effective hypolipidaemic drug. The severity of aortic atherosclerosis as judged by gross grading was more marked in pathogenic, i.e. the hypercholesterolemic group, while animals receiving ginger extract along with cholesterol showed a lower degree of atherosclerosis. The results indicate that ginger is definitely an antihyperlipidaemic agent.

Bhattacharya SK, Kumar A. Effect of Trasina, an ayurvedic herbal formulation, on experimental models of Alzheimer's disease and central cholinergic markers in rats. J Altern Complement Med 1997;3(4):327-36.
Trasina is a herbal formulation of some Indian medicinal plants classified in Ayurveda, the classic Indian system of medicine, as Medhyarasayanas or drugs reputed to improve memory and intellect. Earlier experimental and clinical investigations have indicated that the formulation has a memory-facilitating action. In this investigation, the effect of Trasina, after subchronic administration for 21 days, was assessed on two rodent models simulating some biochemical features known to be associated with Alzheimer's disease (AD). The models, in rats, included intracerebroventricularly (i.c.v.) administered colchicine (15 micrograms/rat) and lesioning of nucleus basalis magnocellularis (nbm) by ibotenic acid (10 micrograms/rat). Retention of an active avoidance response was used as the memory parameter. In addition, the effect of Trasina was evaluated on i.c.v. colchicine-induced depletion of acetylcholine (ACh) concentrations, reduction in choline acetyltransferase (ChAT) activity, and decrease in muscarinic cholinergic receptor (MCR) binding in rat brain frontal cortex and hippocampus. The behavioral and biochemical investigations were done 7, 14, and 21 days after colchicine or ibotenic acid lesioning. Trasina (200 and 500 mg/kg) was administered orally (p.o.) once daily for 21 days, the first drug administration being given just prior to lesioning. Colchicine and ibotenic acid induced marked retention deficit of active avoidance learning that was attenuated in a dose-dependent manner by Trasina after 14 and 21 days of treatment. Frontal cortical and hippocampal ACh concentrations, ChAT activity and MCR binding was significantly reduced after colchicine treatment. Trasina (200 and 500 mg/kg) reversed these deficits after 14 and 21 days of treatment. The findings indicate that the herbal formulation exerts a significant nootropic effect after subchronic treatment that may be due to reversal of perturbed cholinergic function.

Bhattarai NK. Traditional herbal medicines used to treat wounds and injuries in Nepal. Trop Doct 1997;27(Suppl 1):43-7.
In rural Nepalese societies, due to the lack of modern health services and facilities, folk herbal preparations are still the dominant method of therapy for common ailments. These remedies are fairly well accepted, easily available, bear a minimal cost and are generally the only available resource. Information on the curative properties of 42 plant species from 40 genera and 23 families that are used to treat wounds and injuries, has been documented. These herbal remedies are based on ancestral knowledge and personal experience. Their successful use indicates that they are alive and functioning in the rural localities. Although the techniques of preparation of drugs or dosage forms employed by traditional healers have generally been observed to be poor and in most cases do not comply with the requirements of modern pharmaceutical practices, there are trends towards the development and modernization of practice including the standardization of specific dosage, storage of drugs, use of specific types of containers and their labelling. A critical evaluation of the phytochemistry and pharmacology of the alleged curative plants and the traditional pharmaceutical practices employed has been strongly recommended. In rural Nepalese societies, the number and distribution of traditional herbal practitioners and faith healers greatly exceed all other health workers. Their influence should be applied to the task of motivating the rural populace to adopt authentic herbal remedies and other health-related hygienic behaviour.

Birt DF, Mitchell D, Gold B, Pour P, Pinch HC. Inhibition of ultraviolet light induced skin carcinogenesis in SKH-1 mice by apigenin, a plant flavonoid. Anticancer Res 1997;17(1a):85-91.
Apigenin, a widely distributed plant flavonoid, was previously found to inhibit chemically induced ornithine decarboxylase (ODC) activity and skin tumor promotion. The purpose of the present research was to determine if apigenin is effective in the prevention of ultraviolet-B light (UVB) induced skin carcinogenesis. Further studies ascertained if apigenin would be expected to absorb UVB light in a manner to prevent DNA damage in a cell free system. ODC activity was induced with 0.45 J/cm2 ultraviolet A and B (UVA/B) light. Apigenin (5 mumoles/200 microliters DMSO:acetone, 1:9) treatment from 12 hours before until 1 hour following UVA/B exposure was effective in inhibition (25-45% inhibition) of ODC activity measured at 28 hours following UVA/B exposure. Mouse skin carcinogenesis was induced by exposure to a total dose of 40 J/cm2 UVB over 11 weeks. Treatment with 10 mumoles apigenin in 200 microliters DMSO:acetone (1:9) prior to each UVB exposure resulted in reduction in cancer incidence (52% inhibition) and an increase in tumor free survival in comparison with control mice (P < 0.01). Apigenin (0-100 microM) did not prevent the in vitro production of photoproducts in salmon sperm DNA suggesting that apigenin did not inhibit UVA/B induced OD