ADVISORY BOARDS Each issue of HerbaiGram is peer reviewed by various members of our Advisory Boards prior to publication .

American Botanical Council Herb Research Dennis V. C. Awang, Ph.D., F.C.I.C., MediPiont Natural Gail B. Mahadr, Ph.D., Research Assistant Professor, Products Consul~ng Services, Ottowa, Ontario, Conodo Deportment o Medical Chemistry &Pharmacognosy, College of Foundation Pharmacy, University of Illinois, Chicago, Illinois Manuel F. Balandrin, R.Ph., Ph.D., Research Scien~st, NPS Rob McCaleb, President Pharmaceuticals, Salt LakeCity , Utah Robin J. Maries, Ph.D., Associate Professor of Botany, Brandon University, Brandon, Manitoba, Conodo Mi(hael J. Balidt, Ph.D., Director of the lns~tute of Econom ic Glenn Appelt, Ph.D., R.Ph., Author and Profess or Botany, the New York Botanical Gorden, Bronx, New York Dennis J. M(Kenna, Ph.D., Consulting Ethnophormocologist, Emeritus, University of Colorado, and with Boulder Beach Joseph M. Betz, Ph.D., Research Chemist, Center for Food Minneapolis, Minnesota Consulting Group Safety and Applied Nutri~on, Division of Natural Products, Food Daniel E. Moerman, Ph.D., William E. Stirton Professor of John A. Beutler, Ph.D., Natural Products Chemist, and Drug Administro~on , Washington, D.C. Anthropology, University of Michigon/ Deorbom, Dearborn, Michigan Notional Cancer Institute Donald J. Brown, N.D., Director, Natural Products Research Consultants; Faculty, Bastyr University, Seattle, Washington Samuel W. Page, Ph.D., Director, Division of Natural Products, Robert A. Bye, Jr., Ph.D., Professor of Ethnobotony, Notional University of Mexico Thomas J. Carlson, M.S., M.D., Senior Director, Center for Food Safety and Applied Nutri~on , Food and Drug Administro~on , Washington, D.C. Ethnobiomedicol Field Research, ShamanPhormoceu~col s, South Subhuti Dharmananda, Ph.D., Director, lns ~tute for Son Francisco, California Joseph E. Pizzomo, Jr., N.D., President, Bastyr University, Trad itional Medicine and Preventive Health Core Seattle, Washington Jean Carper, Author and syndicated columnist, Washington, D.C. James A. Duke, Ph.D., Economic Botanist (U.S.D.A., Mark J. Plotkin, Ph.D., Author, Executive Director, Ethnobotony ret.) , Herbal Vineyard, Fulton, Maryland Jerry (ott, Ph.D., Chief of Pharmocalogicol Treatment Research and Conservation Team, Arlington, Virginia Program, Notional Instituteof Mental Health, Rockville, Maryland Norman R. Farnsworth, Ph.D., Research Professor of Eloy Rodriguez, Ph.D., James Perkins Professor of Pharmacognosy, Program for Collaborative Research in the Paul Alan Cox, Ph.D., Professor of Botany and Dean of General Environmental Studies, School of Agriculture &Life Sciences, Educo~on and Honors, Brigham Young University, Provo, Utah Pharmaceutical Sciences, and Se nior University Scholar, Cornell University, lthoco, New York University of Illinois ot Chicago Lyle E. Craker, Ph.D., Professor, Deportment of Plant and Soil Sciences, University of Massachusetts, Amherst, Massachusetts James E. Simon, Ph.D., Professor of Horticulture ond Research Ri(hard I. Ford, Ph.D., Professor of Ethnobotony, Director, Center for New Crops &Plant Products, Purdue University of Michigan Edward M. Croom, Jr., Ph.D., Coordinator, Phytomedicine University, West Lafayette, Indiana Project, Notional Center for the Development of Natural Products, David Kroll, Ph.D., Assistant Professor of Pharmacology Beryl Simpson, Ph.D., C. L. Lundell Professor of Botany, University of Mississippi, Oxford, Mississippi and Toxicology, University of Colorado, School of Deportment of Botany, University of Texas ot Austin, Austin, Texas Pharmacy Wade Davis, Ph.D., Author, ethnobotonist, Washington, D.C. S. H. Sohmer, Ph.D., President and Director, Harriet Kuhnlein, Ph.D., Professor of Nutri~on , Steven Dentali, Ph.D., Natural Products Consultant, Botanical Research lns~tute of Texas, Fort Worth, Texas McGill University Portland, Oregon Barbara N. Timmermann, Ph.D., Professor of Pharmacology Hardy Eshbaugh, Ph.D., Professor of Botany &Assistant &To xicology, College of Pharmacy, University of Arizona, Tucson, Albert Leung, Ph.D., Pharmacognosist and Pharmacist, Curator, Willard Sherman Turrell Herbarium, Miami University, Arizona Glen Rock, New Je rsey Oxford, Ohio G. H. Neil Towers, Ph.D., Professor Emeritus, F. R. S. C., Botany Walter Lewis, Ph.D., Professor of Biology, Washington Steven Foster, Botanist, photographer, author, Fayetteville, Deportment, University of British Columbia, Vancouver, British University and Senior Botanist, Missouri Botanical Gardens Arkansas Columbia, Conodo Ara Der Marderosian, Ph.D., Professor of Christopher Hobbs, L.At., AHG, Herbalist, botanist, licensed Arthur 0. Tu(ker, Ph.D., Research Professor of Agriculture and Pharmacognosy, Ph iladelphia College of Pharmacy acupuncturist, Santo Cruz, California Natural Resources, Delaware State University, Dover, Delaware and Science David HoHmann, B. St., M.N.I.M.H., Medical herbalist, Nan(y Turner, Ph.D., Professor and Ethnobotonist, James D. M((hesney, Ph.D., Vice President, Natural Santo Rosa, California Environmental Studies Program, University of Victoria, Victoria, Products Chemistry, NoPro Bio Therapeutics, Boulder, British Columbia, Conodo Mauri(e M. lwu, Ph.D., Bioresources Development ond Colorado Conservo~on Program, Senior Research Associate ot the Division Andrew T. Weil, M.D., Author, Director of the Program in C. Dwayne Ogzewalla, Ph.D., Retired Professor of of Experimental Theropeu~c s, Wolter Reed Army ln s~tu te of lntegra~ve Medicine and Associate Director of the Division of Pharmacognosy, University of Cincinnati Research, Washington, D.C. Social Perspec ~ves in Medicine of the College of Medicine, Un iversity of Arizona, Tucson, Arizona Steven King, Ph.D., Senior Vice President of Ethnobotony and Robert Rountree, M.D., Physician, Boulder, Colorado Conservo~on , Shaman Phormoceu~cols , South Son Francisco, od hoc advisor: E. John Staba, Ph.D., Professor of Pharmacognosy, California David M. Eisenberg, M.D., Director, Center for Alterno~ve University of Minnesota Fredi Kronenberg, Ph.D., Director, Rosenthal Center for Medicine Research, Beth Israel Hospital/Harvard Medical Varro E. Tyler, Ph.D., Dean and Distinguished Professor Alterno~ve/Complementary Medicine, College of Physicians & School, Boston, Massachusetts of Pharmacognosy Emeritus, School of Pharmacy and Surgeons of Columbia University, New York, New York Pharmaceutical Sciences, Purdue University Tom Mabry, Ph.D., Professor of Plant Biochemistry, Deportment Phil Weber, M.D., Physician, Boulder, Colorado of Botany, University of Texas ot Aus~n , Aus~n , Texas Andrew T. Weil, M.D., Author, Director of the Program in lntegra~ve Medicine ond Associate Director of the Division of Social Perspectives in Medicine of the College of Medicine, University of Arizona, Tucson, Arizona

2 • HERBALGRAM No. 40 Educating the Public on the use of Herbs and Phytomedicines DEAR READER As we go to press, several interesting developments have Mark Blumenthal, Executive Director appeared on the regulatory screen. The FDA has released its James A. Duke, Ph.D., Eco nomic Botanist/Author long-awaited proposed regul ations on rna huang, aka ephedra f.tv1ERIUN (U SDA, ret.), Fulton, Maryland (Ephedra sinica). The agency is proposing to allow the contin­ BoT,.AJ\JICAL ued sale of the herb at a reduced maximum unit dosage level at COJNCIL Norman R. Farnsworth, Ph.D., Research Professor of 8 mg of total (ephedra alkaloids, e.g., ephedrine and pseudoephe­ drine), with a maximum total daily ingestion of24 mg, not to be Board of Pharmacog nosy, Program for Collaborative Research in the Pharmaceutical Sciences, University of Illinois at Chicago used for more than seven days. Other limitations also apply. Trustees We include a brief article on this. There is a 75-day comment Varro E. Tyler, Ph.D., Sc. D., Dean and Distinguished Professor period ending August 19, 1997. Predictably, some sellers of of Pharmacognosy Emeritus, School of Pharmacy and ephedra will no doubt object to the low limits and other restric­ Pharmaceutical Sciences, Purdue University tions, which, according to industry hearsay, some people con­ sider not to be based on sound science. Also, breaking just before our press time is the issue of what appears to be accidental adulteration of some lots of the HERBAIGRAM herb plantain with the potentially toxic medicinal plant woolly The Journal of the Ame rican Botonicol Council ond the Herb Research Foundation foxglove, the source of cardioactive glycosides used in medi­ cine. The FDA has received reports of an adverse event involv­ Mork Blumenthal Editor /Publisher ing cardiac complications associated with "Chompers," an herbal Borboro A. Johnston Managing Editor product manufactured by a northern California company. FDA Rob McCaleb Technical Editor research shows that this is not an isolated incident; it relates to Ginger Hudson-Moffei Art Director more than one company's products and has been ongoing for Steven Foster Associate Editor about a year. The traditional herb, plantain, has a long history Downelle Molone Editorial Assistant of safety both as a food and as a medicinal plant in Europe and Ginger Webb Staff Writer the U.S. This ironic event comes at the same time that FDA ha Contributing Editors published proposed good manufacturing practices (GMPs) ini­ Dennis V. C. Awong, Ph .D. Peter Londes tially developed by responsible members of the herb and di­ Woyne Ar mstrong Evelyn Leigh etary supplement industries for FDA review and acceptance. We Koren Deon AlbertY. Leung, Ph.D. cover these issues in our regulatory section. Jomes A. Duke, Ph .D. Aro Der Morderosion, Ph .D. We also introduce the first of a series of monographs pre­ Normon R. Farnsworth, Ph.D. Vo rro E. Tyler, Ph.D. pared by the American Herbal Pharmacopoeia. This opening effort features St. John's Wort (Hypericum perforatum), an item Ch ristopher Hobbs And rewT. Weil, M.D. for which consumer interest is now at an all-time high due to Steven R. King, Ph.D. exposure in a two-page article in a recent issue of Newsweek Subscription/Classified Advertising Manager and a positive segment in a June airing of ABC's 20/20. Our Morgoret Wright feature, "Herbal Monographs," gives an overview of monographs being developed by WHO, USP, ESCOP, ABC, and AHP. The Woli Stopher Copy Editor number and scope of these monographs reflect the interest in Ko ren Newton Editorial Assistant potential health benefits of herbal products and the need for proper identity and quality of such products. Chief Administrative Officer Our essay, "Linnaeus's Garden," takes us on a tour of Woyne Silverman, Ph.D. this green oasis in Uppsala, Sweden. The garden, actually be­ Lindo Prud homme Receptionist gun in 1655 a century before the birth ofLinnaeus, originator of Vickie Adorns Administration the binomial system of plant names, is the repository for 1,300 Joni Weis monn-McCioin Distribution different plants that the master botanist used as his "library." Julie Weismonn-McCioin Information Systems Our book review section includes information on such Cecelia Thompson Accountant diverse volumes as the AHP herbal safety handbook, a discus­ Goyle Engels Sales Coordinator sion of the classic work on plant intoxicants by Baron Ernst von Louren Krzywonski Sales Bibra, an overview of Zulu medicinal plants, and a volume on George Solis Shipping Maori healing-a selection of works to intrigue and inform. Phyl lis Boyd Research Assistant Finally, we also feature, in addition to our usual depart­ H ERIIAIGRAM is published quarterly by the American Botanical Council ments, an account of our Capital Campaign and imminent move and the Herb Research Foundation as an educational project. Both are to our beautiful new headquarters at the Case-Mill Homestead. non-profit research and education organizations under IRS code 501 (c)(3). Educational and business offices are at the American Botanical Council, P.O. Box 201660, Austin, Texas 78720. 51 2/33 1-8868. FAX 512/331- 1924. Subscriptions: $25/yr; $45/2 yrs; $60/3 yrs. Foreign subscriptions, please add $10 per year. © 1997 American Botanical Council. ISSN #0899- 5648. Printed in the U.S.A. HERBALGRAM No. 40 • 3 The Journal of the American Botanical Council and the Herb Research Foundation Number40 • Summer 1997 DEPARTMENTS 6 ABC News 23 Plant Patents ABC Buys Case Mill Homestead; History of Cinnamon; Ciwujia; Piperine; Polyganum Case Mill; Blumenthal Appointed to Pharmacy Professorship; ABC Activities 24 Legal and Regulatory FDA Publishes Proposed Regulations for Good 8 HRF News Manufacturing Practices for Dietary Changes to HRF Professional Advisory Board; Supplements; FDA Proposes Warnings and Sustainable Herb Development Project; Dose Limits on Ephedra; LAPD Issues Kava Commission on Dietary Supplement Labels Retraction ; Industry Alert: Plantain Adulterated Recommendations Report; Recent Publicity for with Digitalis; Commission on Dietary Herbs/HRF; Hotline Information Service Supplements Labels Releases Draft Report to Public 10 Herb Blurbs Rain Forest Diversity; "Chili Sauce" Anesthetic 43 Conference Report for Emperor's Eunuchs? Testing Botanicals; San Francisco Conference of 1996 on Entheogens 11 Media Echinacea in the News(papers); Saponins 49 Market Report Studied for Immune System Influence One-Third of Nation's Adults Use Herbal Remedies; Today's Proactive Consumer and Herbal Supplements; Whole Foods Magazine's 12 Research and World News 2nd Annual Herb Market Survey; Herbalife Echinacea Clinical Study; Course in Medical Tops $1 Billion; Market Report by Peter Landes Herbalism; Botanical Training Program for Retailers; Cox Receives Goldman Environmental Award; HRF Produces Safety Review on Kava S4 Book Excerpts for AHPA Selected excerpts from Plants, People, and Culture by Michael J. Bolick, Ph .D. and Paul 16 Research Reviews Alan Cox, Ph .D. Phytomedicines Outperform Synthetics in Treating Enlarged Prostate; Lycopene in Tomatoes S6 In Memoriam May Help Prevent Prostate Cancer; Citrus Pectin E. H. Bronner, Christopher Hills, Jr., William M . May Inhibit Metastasis of Prostate Cancer; Klein, Jr., James C. Raulston, Benny Simpson Synergistic Action of Pygeum and Nettle Root Extracts in Prostate Disease; Andrographis vs . the Common Cold; Native Foods and Drugs of S9 Book Reviews North America; 63 ABC Catalog Top 10 Book Sales Plants with Antidiabetic 64 Letters Activity; Camptothecin 66 Access and Taxol 66 Calendar 68 Classified 71 Nettle, Edible Wild Weed Ginkgo, Ginkgo bilobo L., Ginkgoaceae. Photo ©1996 Steven Foster. 4 • HERBALGRAM No. 40 St. John's Wort, Hypericum perforatum . Photo © 1997 FEATURES Steven Foster

Pharmacopoeia Londinensis, 1650, courtesy of the Lloyd Library and Museum, Cincinnati, OH. Herbal~onographs Special Section: St. John's Wort ~onograph by Mark Blumenthal 30 § by the American Herbal Pharmacopoeia ™ Linnaeus's Garden by Hakon Tunon 39 Great Botanists/Herbalists Series

Carl Linnaeus's summer garden in Hammarby, Sweden. Photo by Hokan Tunon

Cover: St. John's Wort, Hypericum perforatum l., Guttiferae. Photo © 1997 Steven Foster. See special section between pages 38 and 39 for the Am erican Herbal Pharmacopoeia's™ monograph . HERBALGRAM is printed on recycled paper. 0 HERBALGRAM No. 40 • 5 ABC NEWS

ABC Buys Case Mill Homestead The History of the Enzymatic Therapy, Nature's Way, Nature'sHerbs, and Case Mill Homestead Bio Botonico Are Top Corporate Donors The Ameri can Botanical Council has suc­ $292,000, from indi viduals, fo undati ons, and The Case Mill Homestead has endured cessfull y purchased the Case Mill Home­ members of the herb, supplement, and phar­ through 144 years, as Austin, Texas, changed stead fo r ABC's new Herbal Educati on and maceutical industries. The goal for the en­ from a frontier town into a modern city and Research Center. After the purchase closing tire capital campaign project is $ 1.5 million. engulfed the surrounding farmland. on June 9, ABC staff presented fo under and Blumenthal expressed his appreciation The Coloni al Revival house and ac­ executive director Mark Blumenthal with an for the support the organi zation has received companying mill were built in 1853 on Little oli ve tree to celebrate the event. so far. "We are extremely grateful for the Walnut Creek, four miles fro m what were Minutes before deadline, ABC ex­ level of support we have received from so then the city limits of Austin, a small town ceeded its Phase I funding goal of $ 150,000 many of our fri ends and supporters on this with a populati on of 629, and the new capi­ in 1997 cash and pledges. Total current important milestone in ABC's growth ," he tal of the five-year- old state of Texas. To­ pledges fo r the coming 3-year peri od are said. "Our special thanks go to our fri ends day the 2-1/2 acres on whi ch the house is at Enzymati c Therapy, Nature's Way and situated are embedded in an urban residen­ Nature's Herbs fo r their tremendous gener­ ti al area. The ori ginal 1853 homestead con­ osity in supporting our nonprofit mission. tained 45 1 acres of farmland, all visi ble from These three compani es have contributed the third-story "lookout tower" of the house. nearly half of our pledge total to date," he When clock peddler Sherman Case noted. first proposed building a mill on hi s home­ ABC's new home is about one mile stead, the local Texas Monument newspaper east of the Austin airport and a IS-minute heralded the news as an exciting sign of drive from the Uni versity of Texas and down­ progress. town Austin. The 144-year-old three-story According to an editori al, "Ere long Coloni al Revival house and carriage house many beli eve it is probable Austin will be garage are surrounded by 2-1/2 acres of es­ one of the most fl ouri shing cities in the area, tabli shed herb gardens and li ve oak groves. as it is in locati on decidedl y one of the most As noted in the last issue of Herbal­ beauti ful and interesting. New farm s are Gram, ABC will renovate the hi stori c home continually being opened. Much wheat will and occupy it with administrative offices and be sown the ensuing season. Mr. Case is a bookstore. The carri age house garage will building a fl our mill and expresses himself be converted into storage for Herba/Gram confident, that out of Texas wheat, he will back issues. Renovati ons began in June. be able to make good and white fl our. Mr. ABC intends to occupy the home this fall. Case's mill wi ll be ready for use in a few Future plans fo r the property include weeks, and he has informed us that some two construction of a new building to house ali­ thousand bushels of Travis [County] wheat brary and resource center, an auditorium for are ready to test the efficiency of hi s under­ Above: Side entry to the Case Mill taking." Homestead adjoining one of the educati onal lectures, laboratory space, and sitting areas. additional offices. The new building will be Mr. Case turned out to be a ti ght-fisted Right: Ech inacea designed after the renovati ons and move-in and litigious man (dismi ssed as a "carpet in one of the are completed and when additional donations bagger from up North" by native Texans). herb gardens. are received. 0 He cut timber on his neighbors' land and even Photos by Joni forced the mason who built the mill to sue Weismann­ McCiain. YOU CAN HELP! Herba/Gram readers can help complete this worthwhil e project. To send a pledge or contribution, pl ease use the tear-out card inserted in this issue. Or to request additional informati on, contact Wayne Silverman, Chief Administrati ve Officer of ABC, P. 0 . Box 201660, Austin, Texas, 78720- 1660 ; phone 512/33 1-8868; fax 51 2/33 1-1924; or e-mail : [email protected]

6 • HER BALGRAM No. 40 ABC NEWS

The carriage house of the Case Mill Homestead with herb gardens surrounding . The carri age house will provide much needed space for storage. Photo by Joni Wei smann-McCia in.

him for pay ment. His assets, including the mil l and a li very stable in downtown Austin , CASE MILL changed hands several times while he waged war in court. One of hi s many battles came SPONSOR LIST up before the State Supreme Court. The categories listed below represent giving Willi am Burdett, Mr. Case's partner in levels for Phase I of the Capital Campaign. ABC the mi ll business, was steadi er. He kept the is now seeking multiple-year funding commit­ mill fun ctioning, although on paper it ments to meet the $1 .5 million goal. The changed hands eight times in two years. Hi s companies marked with asteris ks have made son Gil es took over the mill operati on in multi ple-year pledges as of press ti me in June. 1866. Architects - $25,000 and greater Gil es Burdett sometimes appeared in Bio Botanica* the local newspaper because of hi s politi cal Enzymat ic Therapy* acti vities. Mr. Burdett sold the mil l to a man Nature's Herbs* named Chri sti an. He operated the mill fro m Nature's W ay* 1903 to 1905. Nothing more is known about Mr. Christian. Builders - $10,000 to $24,999 Today, no trace of the mi ll remains. Capsugel* Stryker Botanies Co., In c.* Some local elders suppose that Little Wal­ Pharmaton Whole Foods Market* nu t Creek washed it away during one of the Planners - $5,000 to $9,999 area's un predictable floods. Thanks to Cen­ Mark Blument hal General Nutrition Centers (GNC) tral Texas' dramatic hig h-inte nsity rain ­ Cosmopoli tan Trading/Kava Kompani lndena USA In c. storms, the local creeks are known world­ ExtractsPlus Lichtwer Pharma US Inc wide fo r their "fl as h" nature. Fetzer Foundat ion Nature's Bounty In 1905 the house and 451 acres of the Flachsmann Flavou rs & Ext racts surrounding land became the pro perty of Edwin Frame. In 1949, two years after his Supporters- $2,500 to $4,999 widow Maggie Frame's death , 23 1 ac res of Celestial Seasonings Madis Botanicals/Pu re World the "old Frame Place" were purchased by Steven Foster NOW Foods Vern on and Betty Cook. They farmed the Haworth Press Pharmavite land until the mid- l960s, then graduall y sold Ind iana Botanic Gardens Pure Gar most of it off, until the fields and hedgerows Interweave Press around the house had entirely give n way to Friends - $1,000 to $2,499 blacktop and backyards. Vernon Cook, Jr. Ameri can Ingredients New Hope Natural Med ia sold the Homestead to the American Botani ­ Chai NaTa Pharmanex cal Council in June 1997. East Earth Herbs Pharml ine, Inc. ABC is pleased to have "inherited" a Euromed PhytoMed International thorough record of the house's hi story from Flora Manufacturing and Distributing Pro Pac Labs the Cooks. Among the collected papers is a Healthnotes Online Mark Plotki n, Ph.D. newspaper clipping (ca. 1955) that is pure Herb Pharm Pri nce of Peace Enterprises, Inc. Americana. It shows Vernon's two sisters, ages Herbs for Kids QBI - Quality Botanical Ingredients 8 and 9, in long braids and pinafores, pick­ Hilary's Distri bution Traditional Med ici nals ing Texas bluebonnets with the fi ne old house Jason Cosmetics Trout Lake Farm as a backdrop. ABC will preserve the Case Metagenics Tsumura Mill Homestead and the memory of its many Muggenburg Extrakt W akunaga of Ameri ca, In c. occupants as an enduring reli c of Austin 's MW Internat ional David Winston, Herbalist & Alchemist history, while giving th e ve nerable property * Includes pledges for Phase II a new identity and mi ssion . - Betsy Levy ABC reserves the right to alter the giving levels and/ or category na mes with notification. We made every effort to insure the accuarcy ot th is list. Pleas let us know of any errors.

HERBALGRAM No. 40 • 7 ABC NEWS

Blumenthal Appointed to HRF NEWS

Pharmacy Professorship by Rob McCaleb and Evelyn Leigh Mark Blumenthal, founder and executive series, ABC's Botani cal Bookl et series and director of the American Botanical Council , other monographs and review articles, and has received an appointment as Adjunct As­ the German Commission E monographs, as CHANGES TO HRF PROFESSIONAL sociate Professor of Medicinal Chemi stry at well as other publications. ADVISORY BOARD the College of Dr. Davis notes th at the scheduling of Dr. James Ruth, Professor of Medi cinal Pharmacy at The thi s course is a direct result of student re­ Chemi stry at the Uni versity of Colorado in University of quests that such a course be developed, based Boulder, has announced his reluctant resig­ Texas at Austin. on their recogni zing the importance of the nati on from the HRF Professional Advisory The appointment subject matter, and their hav ing heard Pro­ Board. Dr. Ruth, who joined th e Board 14 was m ade this fe ssor Blumenthal speak on thi s subject in years ago, is resigning because the nature of s pring by Dr. the College's Honors Seminar series. 0 hi s research no longer involves the investi­ James T. Dolui sio, gati on of botani cal s for health care. Over Dean of the Col­ the years, Dr. Ruth has demonstrated his sup­ lege of Pharmacy. port of HRF in many ways, including peer Blumenthal ABC Activities review of herb safety review documents and will teach a two­ literature sourcing. HRF is deepl y grateful hour course lim­ January-May, 1997 for hi s dedicated service and will mi ss his ited to 20 fifth­ HIGHLIGHTS OF PRESENTATIONS presence on th e Board. year pha rmacy AND PAPERS BY ABC EXECUTIVE HRF is pleased to announce that David stude nts o n DIRECTOR MARK BLUMENTHAL Kroll, Ph.D., Assistant Professor of Pharma­ "Herbs and Phy­ cology and Toxicology at the Uni versity of tomedi cines" in the fall 1997 semester. Co­ Pharmaton Satellite Symposium on Colorado School of Pharmacy in Denver, has teaching the course will be Dr. Pat Davis, Chemistry, Biological and Pharmacological joined the Professional Advisory Board. Dr. Professor of Medicinal Chemi stry and As­ Properties of Medicinal Plants from the Ameri­ Kroll is a well-known speaker and author of sociate Dean. According to Dr. Davis, the cas, Panama City, Panama, "Criteria for Compari­ more than 30 published papers and abstracts. course fi lled up in the first two days of reg­ son of Phyto medi cines" Hi s work has been funded by the Nati onal American Pharmaceutical Association istrati on for the fall semester, evidence of the Institutes of Health (NIH), the Ameri can Annual Meeting, Los Angeles, Californi a, "Sort­ interest and popularity of the subject of ing Out Altern ati ve Medici ne: Focus on Herbal Cancer Society, and the Cancer League of herbal medicine among pharmacy students. Products" Colorado. He has received numerous teach­ The course is also a prerequisite for students Continuing Education Program for ing awards since he joined the Uni versity of w ho may c hoose a six- wee k electi ve Pharmacists; Harvard Medical School, Guest Colorado in 1992, where he has established rotati on (intern ship) at ABC during their Lecturer, "Alternati ve Med icine: Implications for an herbal medi cine module in the School of sixth year, as part of the experienti al compo­ Clinical Practice," Boston, Massachusetts, "Herbal Pharmacy undergraduate curriculum. Dr. ne nt of the Doctor of Pharmacy degree Therapies," Continuing Ed ucati on Program for Kroll received his B.S. magna cum laude in (Pharm. D.). Phys icians and other health professionals Toxicology from the Philadelphia College of Blumenthal and Davis have developed LSU Hilltop Arboretum, Baton Rouge, Pharmacy and Science and a Ph.D. in Phar­ Loui siana, "Overview of the Rational Use of a course pl an that includes a review of the macology from the University of Florida. Herbal Therapies" history of herbs and medicinal plants in medi­ Complementary Therapies Conference, cine and pharmacy, therapeutic profiles of Seton Hospital Grand Rounds, Austin , Texas, SUPPORTERS NEEDED FOR the major herbs and phytomedicines sold in "Potenti al for Herbs and Phyto- Medicine in Mod­ SUSTAINABLE HERB the U.S. market, legal and regulatory issues ern Clinical Prac tice" DEVELOPMENT PROJECT surrounding the sale and labeling of herbal New Vision International, San Diego, This year, HRF's African international hibis­ products, quality control issues and good Californi a, "Overview of Safety & Acti vity of 20 cus growing project touched the Ii ves of more manufacturing practices, the role of ethno­ Popular Herbs" th an I ,000 people in the impoverished West botany in drug development, and related top­ Round Top Herb Festival, Round Top, Afri can nati on of Mali. In addition to help­ ics. Resource materials will include pharma­ Texas, "The Role of Med icinal Herbs in the United ing farmers, the project provided a source of States" cognosy textbooks, arti cles from Herbal­ hi gh quality, organi c Hibiscus sabdari.ffa L. Gram and ABC's Classic Botanical Reprints (Malvaceae), one of the most popular herbal continued on page 65

8 • HERBALGRAM No. 40 HRF NEWS

tea ingredients on the market. Project sup­ tion. "The report points out that most mod­ NBC Dateline aired a segment on gar­ porters are hoping that the hibiscus project ern nations have a means of all owing more lic on April II that featured an interview with will double in scope next year, involving forthright claims for medicinal use of herbs," Rob McCaleb, filmed last August in San twice as many farmers and producing twice McCaleb remarked. Francisco. McCaleb spoke briefly on the as much hibiscus. Clearly, there is great po­ health benefits of garlic and was shown tential fo r herbs to become one of the most RECENT PUBLICITY FOR working on the layout of HRF's Garlic Herb important cash crops for farmers in the Niger HERBS AND HRF Information Brochure. Ri ver Valley, and plans for a similar cultiva­ HRF president Rob McCaleb was quoted in tion project in South Africa are already tak­ the May 5, 1997, issue of Newsweek in a posi­ NEW LOWER COST FOR HOTLINE ing shape. HRF hopes to expand the entire tive, high-profile article on the benefits of INFORMATION SERVICE project to include other herbs and other coun­ St. John's Wort (Hypericum peiforatum) in The minimum cost for a Natural Healthcare tries in Africa and elsewhere. the treatment of depression. In the article, Hotline information call has been lowered Currently, HRF is extending an invi­ "A Natural Mood Booster," McCaleb called to only $5 from the former minimum charge tation to herb companies interested in sup­ Hypericum the "premier herb for depres­ of $10. An important future goal for HRF is porting this socially and environmentall y sion." The article presents a number of fa­ to obtain adequate funding to offer the responsible herb development project. Com­ vorable patient testimonials, a review of the Hotline as a free service, but, until that day, panies can participate by agreeing to pur­ clinical evidence on Hypericum, and bal­ it is necessary to charge this minimal fee to chase herb crops, by contracting with project anced safety information. According to the cover the costs of database management and farmers to grow specific herbs, or by pro­ artic le, the National Institute of Mental Hotline operation. HRF individual members viding technical assistance, seeds, specifica­ Health and the Office of Alternative Medi­ pay only $.95 per minute to talk to an infor­ tions, or fund ing. cine are currently planning a large, mation speciali st with access to HRF's pro­ multicenter clinical trial to evaluate the effi­ fessional database of facts on more than 170 COMMISSION ON DIETARY cacy and safety of St. John's Wort in depres­ herbs. on-member cost is $1 .50 per minute. SUPPLEMENT LABELS RELEASES sion. Discounts on Hotline usage increase DRAFT OF RECOMMENDATIONS On March 25, CNBC (the cable affili­ with level of membership, and higher-level REPORT ate of NBC) ai red a program on the subject HRF members may take advantage of a The Commission on Dietary Supplement of dietary supplement marketing and regu­ unique Hotline subscription service. This Labels (CDSL) has released a preliminary lation. The main topic of discussion was the valuable educational resource allows sub­ draft version of its recommendations on sale of dietary supplements that may reduce scribers to refer their customers' questions supplement labeling policy. At this time, the the ri sks of serious health conditions. The to a dedicated toll-free number providing presidentiall y appointed commission is seek­ debate was sparked by Cholestin, a dietary direct access to Hotline Information Special­ ing public comment and corrections to the supplement manufactured by Pharmanex, ists. Information Specialists are trained to draft before finalizing the document for sub­ Inc. Product claims state that Cholestin can offer accurate, unbiased facts on herbs and mission to President Clinton, Congress, and lower cholesterol levels. other natural products without diagnosing, the Secretary of Health and Human Services. The show featured a live satellite in­ prescribing, or recommending any specific The CDSL hopes to release its completed terview with Pharmanex president William product or brand. To find out more about report in August 1997. (For a conference McGlashan, Jr., followed by satellite inter­ the benefits of Hotline subscription, contact report see page 43.) views with HRF president Rob McCaleb and Margaret Blank at HRF. The draft report takes into account Dr. Raymond Woosley, Chairman of the To access the Hotline, call HRF at 303/ public testimony presented at a series of open Pharmacology Department at Georgetown 449-2265 and ask for a Hotline Information meetings last year, as well as recommenda­ University Medical School and a freq uent Specialist. tions made by CDSL subcommittees address­ consultant to the FDA. Accordi ng to ing specific regulatory issues. McCaleb, "Dr. Woosley faithfully dispensed According to HRF President Rob the FDA party line belief that FDA should McCaleb, who has served on the commis­ have the fi nal word on all health-related sion si nce hi s appointment in November products." McCaleb held fast to his own 1995, the primary intent of the commission's belief that " ... the public wants the right to report is to help educate Congress about choose safe, effective, self-care products, major issues in dietary supplement regula- including those that can reduce the risks of serious diseases."

HERBALGRAM No. 40 • 9 HERB BLURBS

Rain Forest Diversity

According to ecologists, a small2.5 acre First settled by the Portuguese patch of Brazilian rain forest contains about 500 years ago, the forest has been 476 tree species, more than any spot of hard hit by civilization: ecologists esti­ similar size ever studied. The number mate that only five percent of the origi­ of species on a similar patch of North nal forest remains. Among other items American temperate forest contains found as a result of a study conducted only two to 20 tree species. The study by the Uni versidade Estadual Paulista area, about 300 miles northeast of Ri o in Brazil are 104 tree species that had de Janeiro, is part of an ecosystem most never been seen in the Atlantic coastal often ci ted as one of the world's most forest and five that are completely new endangered. to science. That number could increase Dr. Russell Mittermeier, presi­ as the results of the study are analyzed dent of Conservati on International, said more completely, according to Dr. Wayt at a meeting of the Atlantic Forest Eco­ A view of rainforest canopy. Photo by Thomas of The New York Botanical logical Corridors Workshop, "It just re-em­ Elmonette Bivens, a participant in one of Garden. "It provides a little snapshot of the phasizes how important these threatened hot ABC's Pharmacy From The Rainforest forest," Dr. Thomas said. -Barbara A. spot areas are." The meeting was held in the ethnobotanical tours . See the enclosed Johnston fa ll of 1996 in the Brazilian state of Bahi a. Herbal Education Catalog for more [Austin American-Statesman, 1996. November information on tours sponsored by ABC 12.] and the Texas Pharmacy Foundation. "Chili Sauce" Anesthetic for Emperor's Eunuchs? Sun Yaoting, the last eunuch to serve in the chuan jiao ("Sichuan spice") or hua jiao concen-tration. All the component drugs court of the last Manchu Emperor of China, ("flower spice") is Sichuan peppercorn have analgesic effects. died in December in Beijing. He was al­ (Zanthoxylum bungeanum Maxim. or other In 1877, a British official stationed most 94. According to an article in the New Zanthoxylum sp., Rutaceae). The use of in China presented a paper to the Royal York Times, the process employed at the both pepper and Sichuan peppercorn in lo­ Asiatic Society, describing the eunuch clinic time he was castrated in 1911 used "onl y cal and general anesthetic preparations in of the Manchu Dynasty. He reports that hot chili sauce as a local anestheti c .... " China has been well documented; but not before castration, the patient was given a According to Albert Leung, Ph.D. , "I so with chili pepper. And Sichuan pepper­ bowl of "nerve-stunning" herbal tea, and wouldn't be surprised that the original au­ corn is also well-known for its "ma" or locally desensitized with baths of hot pep­ thor [meant] black or white pepper and numbing properties. per water. Sichuan peppercorn, all of which have one The practice of employing eunuchs Chili peppers (Capsicum spp., Solan­ word in common, namely "jiao," or spice. in the imperial palaces of China dates back aceae), long used as a spice and in prepa­ La jiao ("pungent spice") is chili pepper, over two thousand years. Hi storically, few rations such as ointment and liniment, ori gi­ hujuajiao ("foreign spice") is black/white details survive concerning the surgical pro­ nated in South America, and didn't arrive pepper (Piper nigrum L., Piperaceae), and cedure itself. Hua T'o [Tuo], a famous in China until the mid-sixteenth century, Chinese surgeon whose writings became after following the silk trade routes from known around 190 A.D., and known for hi s the Middle East. Capsaicin, the primary castration method, was said to have used a active compound in chilies, has been shown drug di ssolved in wine as a general anes­ to have topical analgesic activity. thesia before hi s operations. At that time [S ources: Anderson, Mary M. 1990. Hidden the ingredients of ma-fei-san, which means Power: The Palace Eunuchs of Imperial "bubbling drug medicine," were still uni­ China, Prometheus Books, Buffalo , NY. dentified. However, according to Dr. Andrews, J. 1995. Peppers: Th e Domesticated Leung, Hua Tuo's ma fei san contains Capsicum, Uni versity of Texas Press, Austin . Anonymous. 1996. Chili peppers help ease danggui (Angelica sinensis (Oiiv.) Diels. surgery pain. Austin American Statesman, May Apiaceae), yangzhizhu (Rhododendron 2 I. Faison, S. I 996. The Death of the Last molle fl owers , Ericaceae), moligen Emperor's Last Eu nuch. New York Times, Dec. (Jasminum sambac (L.) Aiton, Oleaceae 20. Veith, ll za. 1970. Huang Ti Nei Ching Su Chilies, Cap~icum annuum . Photo © 1997 root), and changpu (Acarus gramineaus L., Wen: The Yellow Emperor's Classic of Inter­ Anaceae rhizome), in decreasing order of nal Medicine, University of California Press, Berkeley.] 10 • HERBAL GRAM No. 40 MEDIA

Echinacea in the News( papers)

Echinacea is a word that most people can soft news day for newspapers, and th e Jour­ These three mainstream newspaper now pronounce, despite the class ical Latin nal managed to fill at least a foo t of column arti cles on Ec hinacea and other herbs em­ pronunciati on which turns the "ch" in the first space with what was essenti all y fluff. phasize the avail ability of herbs in the mass sy ll abl e to a hard consonant "k". Perhaps In a pi ece entitled "The rush is on to market for consumer researching altern ati ve Echinacea is becoming part of the nati onal Echinacea," Judy Foreman ex pl ored the sub­ approaches to their health care. - Steven psyche. Recent articles on Echinacea in such ject in the "Health Sense" column in the May Foster stori ed newspapers as Th e Wa ll Street Jour­ 17, 1997, iss ue of the Boston Globe. This ar­ nal, Th e Boston Globe, and Th e Detroit News ticle included much more in fo rmati on on the all point to this wellknown herb becoming a pros and con s of Ec hinacea, citing in detail a mainstream Ameri can cold remedy. number of German studi es. Several medi ci­ Page one of the Monday, Janu ary 20th, nal pl ant re searchers, in cluding Cath y 1997, Wall Street Journal carried a story Crandall at Washington Uni versity, St. Louis, Saponins Studied for "Echinacea: Does it Cure What Pail s Ya? Gail Mahady at the Uni ve rsity of Illinois, Indians Thought So," by staff writers Ellen Chicago, and recentl y reti red Purdue phar­ Immune System Influence Joan Poll ak and Michael Moss who took a macognos ist Yarro Tyler are interviewed for Saponins are a cl ass of chemicals fo und in li ght approach to the subject. Interviewing th e piece, ex pressing guarded optimism on many plant s, parti cul arl y legumes, whi ch a bank manager, MTV executi ve, book pub­ th e results of research. Dr. Tyler is quoted as gained their name by forming a soap-like li sher, and a nay-say ing lawyer, the Journal saying Echinacea "is one of the fe w herbs I froth when shaken with water. They are be­ reported th at Ec hinacea had jumped to the take." Two Newton, Massachu sett,s ph ys i­ ing studied extensively fo r th eir ability to nati onwide marketpl ace in va ri ous chain cians, Dr. Carol Englender and Dr. Edward stimul ate the immune system, lower choles­ drug stores and health food store chain s. Chapman, both recommend that their patients terol, and fi ght bacteri al and fun gal infec­ Mi chae l McC uffin and Janet Zand of use Echinacea. The arti cle was we ll re­ ti ons and cancer, as we ll as for their spermi ­ McZand Herbals, who reported that their searched and contain ed the sa lient points that cidal acti vity and their potenti al as a sugar Echinacea sales increased by 25 percent m a co nsumer mi ght ex pect to know about substitute. 1996 to over $ 10 million, we re the onl y Echinacea, including di sc uss ion on spec ies In Japa n, saponins deri ved fro m Panax manu fac turers whose interview was pub­ differences, Germ an Commi ss ion E recom­ vietnamensis Ha & Grushv., Araliaceae (Viet­ li shed. Herb Pharm and Nature's Answer's mendati ons, and dosages. namese gin seng) have shown ac ti vi ty fo r Echinacea produ cts we re also menti oned in The Wedn esday, February 19, 1997, is­ a di sc ussion on dosage. Santa Moni ca, Cali ­ sue of Th e Detroit News fea tured an article forni a pedi atri cian Jay Gordon, interviewed on Echinacea by Tracy L. Pipp. "Stopped for th e piece, notes that he now prescribes Cold- Echinacea is the hot new remedy that Echinacea. Presumabl y to add a "balanced has herbal medicine fa ns all atingle," focused approach" to the story, Dr. Philip Askenasem, more on the industry and market perspecti ves a professor of immunology at Yale Medical of the herb . Indu stry luminari es interviewed School, who may or may not know how to for the piece included Marguerite Smith of pronounce or spell Ec hinacea (or pres umabl y Amway, Peggy Brevoort of East Earth Herbs, is unfamili ar with the literature) was inter­ Jeff Morri son of th e Ameri can Herb al Prod­ viewed, and cautiously warned consumers ucts Associati on, and the Ameri can Botani­ not to foo l themselves into beli ev ing any­ cal Council's Way ne Sil verman. In additi on thing at health food stores could boost th eir to Echinacea, other herbs featured in the immune systems. German research is men­ piece included St. John 's wort, kava, ginkgo, tioned in pass ing in a paragraph in which the and saw palmetto. Dr. Charl es McClos key, writers mention only Echinacea angustifolia director of outpatient care at Oakl and Gen­ by name, while citing a clinical stud y con­ eral Hospital in Madi son Heights, Michi gan, ducted on Echinacea purpurea. The illus­ and Dr. Jenni fe r Jacobs, a Seattle ph ysician, trati on that appeared on the front page of the gave Echinacea a cauti ous thumb's-up, de­ newspaper, incidentall y, was the fe derall y spite th e fact that clinical studi es have been li sted end angered species Echinacea limited to Germany rather th an conducted in tennesseensis, th ough there was no mention th e United States. of it or conservati on issues. Monday is the Chinese Honey Locust, Gleditsia sinensis. Photo ©1988 Steven Foster.

HERBALGRAM No. 40 • 11 MEDIA

countering fatigue, bone pain, and arterio­ against rattlesnake venom and as an anti­ gal) infections so often found in people with sclerosis; for improving appetite, muscle tumor agent. AIDS. As antifungal agents, saponins are force, and memory; and improving the qual­ The National Cancer Institute has being studied in Great Britain for their po­ ity of sleep. shown that saponins from the tropical tential role in resisting plant disease in agri­ Cambridge Biotech of Cambridge, Archidendron ellipticum (Blume) Niels, culture. Other studies exploring the great Massachusetts, is focusing on the immunity Fabaceae can act as an antitumor agent in potential of these plant compounds are un­ boosting properties of QS-21 , a saponin de­ renal cancer cells. Other researchers at Kyo to der way. According to Albert Leung, Ph.D., rived from the Quillaja saponaria Molina, Pharmaceutical University report anti-tumor "Saponins are a very broad class of com­ Rosaceae (Soap bark tree) bark, and related effects with a saponin derived from Gleditsia pounds, some of which are very toxic."­ compounds. The company plans to combine japonica Miq., Fabaceae (Japanese honey Ginger Webb. QS-21 with vaccines so that an immune re­ locust). [Dutton, Gail. Saponins Draw Interest as Boost­ sponse will be triggered when the vaccine is Researchers at Hebrew University ers of Immune System. Genetic Engineering given. In Brazil, immunologists are also have found that G2, a saponin derived from News, Vol. 18, No.5, March l, 1996, I, 32. studying a saponin from Q. saponaria for its alfalfa roots (Medicago sativa L., Fabaceae), Leung, A., 1996. Personal communication. No­ vember 30.] potential as an immunization component may be helpful in fighting the mycotic (fun-

RESEARCH AND WORLD NEWS Echinacea Clinical Study Course In The Bastyr University Research Institute for more than a century, is one of the most announced in February that it is beginning a commonly used medicinal herbs in this Medical Herbolism clinical study of the herb Echinacea. The country. Its apparent capacity to stimulate Every four to six weeks, conventionally study, expected to last 16 months, is the first the immune system shows promise as a treat­ trained M.D.s, nurse practitioners, and chi­ of its kind in this country and will look at ment for mjnor and severe infections. If we ropractors are gathering in Calistoga, Cali­ the effectiveness of Echinacea on the fre­ can show that Echinacea is effective in fornia, at the Institute of Medical Herbal ism quency and severity of respiratory tract in­ reducing the number and severity of to learn the fine points of botanical medi­ fections. The study is being funded by respiratory infections, then we will have a cine from Dr. Mary Bove and Dr. Jane Madaus AG of Cologne, Germany. non-harmful immune system stimulator Guiltinan-both Naturopathic physicians According to Carlo Calabrese, N.D., which may provide a viable alternative and graduates of Bastyr University. In addi­ MPH, Principal Investigator for the study and to antibiotics." tion, Dr. Bove is a graduate of the School of Co-Director of the Research Institute, Volunteers are currently being re­ Phytotherapy in London with well over "Echinacea, a staple of botanical medicine cruited from the greater Seattle area. They twenty years experience working with herbal wi II be prescreened by telephone and must medicines. meet inclusion criteria to participate in Says Dr. Nancy Welliver, founder and the study. These criteria include: expe­ director of the Institute, also a graduate of riencing three or more respiratory infec­ Bastyr, "I've seen so many well-intentioned tions within the last six months; four or M.D.s and other health professionals strug­ more respiratory infections within the gling with botanical medicine. This is the last 12 months; or chronic respiratory in­ only comprehensive course designed strictly fections. for the health professional. There are many For further information call 206/ good schools of herbal medicine in the U.S,. 365-3130. Media requests to Terri Sil­ but all are directed toward the lay public. I ver, 206/602-3103. believe that a medical professional needs a higher level of training and ideally would get that training from another experienced health professional. The only other option is to Echinacea, Echinacea angustifolia. enroll in one of the accredited Naturopathic Photo © 1996 Steven Foster. schools and most professionals are not able to put aside their practice to go back to school."

12 • HERBALGRAM No. 40 RESEARCH AND WORLD NEWS

The first class of the Institute began in February of 1997. A Level I class for the Cox Receives Goldman Environmental Award East Coast and an Ayurvedic class to be Paul Cox, professor of ethnobotany at managed ecotouri sm plan. In addition, Cox taught in Calistoga begin in the fall of 1997. Brigham Young Uni versity, has received the continues the work th at first brought him to An advanced course is scheduled for 1998. Goldman Environmental Prize for grassroots the forest, the search for new plant-based The curriculum for the Level I class includes environmentalism. The prize, which Time medicines. the most common and effective herbs for magazine has referred to as sort of a "Nobel One product of that research is the dis­ each body system, dosing, toxicities, and in­ Prize" of environmental activism, is given covery of prostratin, a substance derived teracti ons with pharmaceuticals. In addi­ annually. Cox shares the award with Chief from the bark of a rainforest tree, tion, special topics such as HIV, pediatrics, Fuiono Senio for their joint efforts to save Homalanthus nutans A. Juss. Euphor­ and herbal product preparation are covered. the 30,000-acre Falealupo rain forest in West­ biaceae. Cox learned of the substance from The Ayurvedic class, taught by Dr. Vivek ern Samoa. The two men met while Cox was Samoan medicine women, who were using Shanbhag, N.D. , M.D. (Ayurved), will cover li ving in Western Samoa, conducting ethno­ it to treat hepatitis. In preliminary tests, the basics of Ayurvedic diagnosis and the botanical research in the vi ll age ofFalealupo. prostratin showed promise as an anti-AIDS common herbal and dietary treatments used Professor Cox will use hi s portion of treatment and the National Cancer Institute in Ayurveda. the award-$37 ,500-to establish an endow­ is in vestigating its potential as a drug candi­ Contact the Institute of Medical ment through the Seacology Foundation, date. If it is ever used as a drug, patent agree­ Herbal ism at 707/942- 1250, or P.O. Box formed to help save indigenous rain forests ments guarantee that the Samoan people will 1149, Calistoga, CA 94515. The dates for the from destruction; the foundation wi ll use the receive a share of any profits. Ayurvedic class are: Sept. 12-14, Oct 17-19, funds to endow the rain forest and support Gary Hume, president of ature's Nov. 2 1-23, 1997. The course hours total 54. local environmental efforts. The Falealupo Way, announced that his company has rain forest is the first of its kind to be en­ matched Professor Cox's award to increase dowed with funds to protect it from outside the endowment fund. Seacology Foundation development pressures. Dr. Cox was instru­ wi ll administer the fund. Nature's Way has Botanical Training mental in preservi ng the Falealupo rain for­ provided both leadership and fi nancial sup­ est by raising the funds needed to help the port to the fou ndation. Program for Retailers village build a school for its children, obvi­ In addition, Joseph Ogden of Nu Skin, In January 1997, the Rocky Mountain Cen­ ating the need to sell the rain forest timber. International announced that the company ter for Botanical Studies in Boulder, Colo­ The forest is now protected by a unique will also match the 37,500 award. Cox has rado, created an educational program entitled permanent covenant, in which the indigenous deposited $11,250 into funds whose interest Herbal Supplements Retail Training Pro­ people maintain stewardship. While the cov­ will be donated annually to Falealupo Vil­ gram, a course tailored specifically to ques­ enant forbids logging or destructive commer­ lage and Tafua Rain Forest Preserves for tions and challenges faced by retail employ­ cial development, villagers can still use the trails, signs, and other needed maintenance. ees who work in Health and Beauty Aids forest as they have for centuries. (See Herb­ (HABA) departments in health food stores. a/Gram No. 36, p. 24.) In addition to the several basic herb courses Cox, who became honorary chief of the schedule includes seven classes address­ the village for hi s work, has continued to ing specific retail needs and issues in the ar­ volunteer assistance to help the village cul­ eas of herbs and herbal products, such as tivate long-term sources of income. In May reading and evaluating product labels, guide­ 1997, the village dedicated a new aerial lines for legal discussion of health concerns rainforest walkway, as part of a carefull y with customers, and retailer customer screen­ ing protocol. According to Feather Jones, program coordinator, the need for informed sales people in health food stores has never been greater. "Safe sales, [with regard to label requirements and claims of effective­ ness] are particularly important because of Left: Paul Cox works with Dr. Kimberly the vulnerability of the retailer to legal and Johnson, a Colorado physician, and Gary Booth, a BYU zoology professor, in the reg ul ~ tory scrutiny," she said. For additional ra inforests of Western Samoa. information on the course, contact the Rocky Above: Paul Cox studyi ng plants while Mountain Center for Botani cal Studies, 303/ conducting ethnobotanical research in the 442-6861. - Barbara A. Johnston rainforests of Western Samoa . Ph otos by [Natural Food Merchandiser, December 1996. Mark Ph ilbrick, BYU . 56.]

HERBALG RAM No. 40 • 13 RESEARCH AND WORLD NEWS

HRF Produces Safety Review on Kava for AH PA by Steven Dentali, Ph.D.

The process of integration between botani­ One useful document in this regard, a sort a botani cal is appreciated and attended to cals and human cultural practices takes of background check, is a review of the in a manner consistent with its veneration many forms. It appears that kava's first available literature on kava, critically evalu­ as a vital spiritual substance. Until recently use resulted from direct experimentation by ated with an eye to the safety of large-scale kava was kava to outsiders while the Pa­ people arriving in the land where kava al­ kava consumption. In order to produce this cific islanders knew, and named, more than ready existed. New people, new land, new document the American Herbal Products 110 different varieties distinguishable by pl ants. Current kava use in the United Association commissioned the Herb Re­ appearance and subjective effects. States might be described as new market. search Foundation to create an Herb Safety The relatively recent work of Vincent Integrating kava into the American culture Review on kava, which I authored. Lebot, Ph.D. , indicates that kava exists as requires groundwork in addition to that The Kava Herb Safety Review is a nine di stinct chemotypes (chemical variet­ needed literally to propagate the supply of technical document of 29 pages including ies). It now appears quite clear that humans new plants. 85 references. It provides a short descrip­ have taken this plant from the wild, grown Kava (Piper methysticum, Forst., tion of kava and kava use, covering its ori­ it, consumed it, and selected for the prop­ Piperaceae), poised to make its American gin , distribution, and hi story. Greater at­ erties they prefer. In this way they have debut, needs some paper attesting to its di s­ tention is given to the chemi stry of kava, molded the original plant into distinct do­ position, upbringing, and training, as it including the chemical variations among mesti cated varieties. Lebot has also shown were. What behavior are manufacturers and cultivars (varieties), its toxicology and that there is insufficient evidence to con­ di stributors of kava products to expect from physiological effects. Recommendations sider kava as a separate species from its wild their ingenue once on the societal register? on appropriate dose limitations and warn- ancestor. ings for kava are also presented. The second theme that stands out is The Review was peer-reviewed the lack of abundant information on by four qualified reviewers: Marilyn kavalactones. Having been trained as a Barrett, Ph.D., Steven Foster, Vincent medicinal chemist, it is clear to me that Lebot, Ph.D., and Andrew Weil, M.D. much work remains to be done on this fas­ Their comments and credentials along cinating class of biologically active mol­ with the credentials of the author are ecules. At the very least they deserve men­ included as appendices to the review. tion in standard texts of organic medicinal I would like to present two and pharmaceutical chemistry. themes that I found to be especially en­ The question of what the U.S. mar­ lightening while researching the litera­ ket will make of kava remains. I will, with ture on kava. The first has to do with the greatest of interest, watch this new­ the involvement of native peoples in comer to our society climb the herbal so­ kava selection, the second with the ac­ cial ladder. Kava, a product of human ac­ ti ve kavalactones as separate entities. tivity in the South Pacific, is about to be Certain themes have a way of shaped anew in North America. arising when one looks deeply into a I would like to thank the Herb Re­ particular issue. ·One theme of kava is search Foundation for the opportunity to the defining role it holds in many South author the Herb Safety Review on kava and, Pacific communities. Kava has taken in particular, Margaret Blank, who obtained on a social significance at least as great and organized the materials for my review, as that of alcohol in Western culture, and Evelyn Leigh, whose editorial hand but, unlike alcohol (except for the greatly improved the original document. Christian mass), is traditionally used in The Kava Herb Safety Review was spiritually oriented ceremonies. Be­ funded through industry donation and is yond this profound in volvement of kava available from AHPA through a similar con­ in spiritual ceremony and healing, ar­ tribution. eas not covered in this review, kava as For more information, contact AHPA, 4733 Bethesda Ave., #345, P 0. Box 30585, Bethesda, MD 20824-0585. Ph. 301/951- 3204. Fax 301/95 1-3205. email: ...Y ~l.h"1 btzWNtVJIJ . Kava, Piper methysticum, by Sydney AHPA @ix.netcom.com 21,_. (, :~ '[<., ... Parkinson, 1769. Courtesy of The Natural Hi story Museum, london.

14 • HERBALGRAM No. 40 Manufacturer~! Make sure you are covered! The Dietary Supplemen l;lealth and Education Act allows herbal product manufacturers to make "structure/function" claims about the effec ucts have on the structure or function of the human body. lhese claims may be made under the following four conditions:

Drawing on a library of OVf!A 100,000 scientifiq articles and an International netwak of co tacts the Herb Research Foundation offers custom research on spect of herbs, spices, medicinal plants and essential oils: • Health benefits of herbs • Regulatory information • Herb horticulture • Herb safety research

From a few pages to comprehensive background literature, we provide online database searching, complete scientific articles and references, access to experts, consultants and more. Get the facts!

For fee schedules and member discounts, phone HRF at (303)449-2265 or write us at:

1007 Pearl Street, Suite 200 . Boulder, CO 80302 Phone 303/449-2265 · Fax 303/449-7849

HERBALGRAM No. 40 • 15 RESEARCH REVIEWS

Phytomedicines Outperform Synthetics In Treating Enlarged Prostate One of the great success stories in botanical medicine is the Euro­ the reported improvement in quality of life, "which was reflected in pean use of phytomedicines in treating enlarged prostate, or benign the over 80 percent good to very good efficacy judgements." Saw prostatic hyperplasia (BPH). The condition, which affects roughly palmetto is approved by the German government Commission E as half of men over 60 years of age, reduces quality of life by causing a treatment for BPH, as are extracts of nettle roots ( Urtica dioica L. , frequent urination, nighttime awakenings, and other urinary diffi­ Urticaceae) and pumpkin seeds (Cucurbita pepo L. , Cucurbitaceae). culties. Standard American therapy consists primarily of treatment The proposed mechanisms of actions for these phytomedicines are with sy nthetic prescription drugs, which can have significant side regulation of hormone metabolism, immune system mediation, effects. In contrast, European treatment frequently substitutes the anticongestive actions, and effects on the muscles of the bladder. use of medicinal plant preparations with very good clinical support The authors conclude that in terms of increasing urinary flow and a superior safety record. rate, "the data show a clear superiority of the saba] [saw palmetto] This comparative review discusses results of a number of stud­ extract in comparison to the synthetic drugs." For Proscar, ies in vestigating the effectiveness and safety of phytomedicines and (fi nasteride), only one-third of the treated patients had "clinically synthetic drugs in the treatment of BPH, with a focus on saw pal­ relevant improvement," and only after at least six months of treat­ metto (Serenoa repens (Bartr.) Small, Arecaceae). During the course ment (n=533). They also note that one of the drugs used in conven­ of one three-year trial involving 309 men, saw palmetto was associ­ tional medicine, alfuzosin, produced a short-term improvement in ated with a significant increase in urinary flow rate (6.1 ml per sec­ the first year of the study, followed by a "striking" decline in the ond) and a 50 percent decrease in residual urine volume. In com­ second year. parison, the American prescription drug Proscar® (finasteride) Clearly, saw palmetto offers superior symptomatic relief in showed a 30 percent decrease in symptom scores over three years, prostate disease, as defined by the most common clinical tests. In but urine flow improved only slightly, and residual urine volume addition, it improves quality of life and has a "practically negligible was almost unchanged. Further, 10.7 percent of finasteride patients side effect risk." This review makes a compelling case for the use of discontinued treatment because of side effects, compared to only saw palmetto as the treatment of choice among physicians and pa­ 1.8 percent of those taking saw palmetto. Perhaps most important is tients concerned with meaningful improvement and greater safety compared with conventional syn­ thetic drugs. While cost was not a consideration in this review, saw palmetto extract is also sig­ nificantly less expensive than conventional prescription drugs. - Rob McCaleb [Bach, D. , Schmitt, M. , and Ebeling, L. 1997. Phytopharmaceutical and synthetic agents in the treatment of beni gn prostatic hyperplasia (BPH). Phytomedicine 3/4: 309-3 13.]

Saw palmeHo fruit, Serenoa repens . Ph oto © 1997 Steven Foster.

16 • HER BALGRAM No. 40 RESEARCH REVIEWS

Lycopene in Tomatoes May Help Prevent Prostate Cancer

The relationship between the risk of prostate cancer and the intake prostate cancer risk. Of these four, three are primary sources of of specific carotenoids, retinol (vitamin A 1), fruits, and vegetables lycopene: tomato sauce, tomatoes, and pizza. The fourth significant was examined in a prospective cohort study (a study of likely food item was strawberries. The researchers suggest that this may candidates from a particular group). The dietary intake of 47,894 be an anomaly and note that the red color of strawberries is not men (initially free of diagnosed cancer) was pull ed from a 1986 due to lycopene. Tomato juice, the other major source of lycopene, food-frequency questionnaire, and follow-up questionnaires were showed no correlation to prostate cancer risk. The findings suggest sent out in 1988, 1990, and 1992. Within that time period, 812 that intake of Iycopenes and other compounds found in tomatoes new cases of prostate cancer were documented among the subjects. and tomato products may reduce the risk of prostate cancer. The The food-frequency data and the prostate cancer data were other carotenoids measured in this study were unrelated to risk, as analyzed. was dietary retinol. The findings support general cancer-prevention The results show that of the carotenoids (a class of yellow recommendations to increase fruit and vegetable consumption, and to deep red, highly unsaturated pigments occurring in many suggest that consumption of tomato-based products may be of vegetable oils and some animal fats), neither alpha-carotene, beta­ special benefit in preventing prostate cancer. -Ginger Webb carotene, lutein, nor beta-cryptoxanthin intakes were significantly [Giovannucci , E. , A. Ascherio. E. B. Rimm , M. J. Stampfer, G. A. Colditz, associated with risk of prostate cancer. However, lycopene, the and W. C. Willett . December 6, 1995 . Intake of Carotenoids and Retinol carotenoid that makes tomatoes (Lycopersicon esculentum Miller, in Relation to Risk of Prostate Cancer. Journal of the National Cancer Institute, Vol. 87, No. 23 , Dec. 6. 1767-1776. Solanaceae) red, showed a significant inverse correlation to prostate Anonymous. 1995. Tomatoes Found to Reduce Risk of Cancer. New York cancer risk, with the degree of correlation differing with high and Times, December 7. low intake. Of the 46 fruits, vegetables, and related products on Anonymous. 1996. Study Shows Lycopene May Prevent Prostate Cancer. the questionnaire, four showed a significant inverse correlation to HealTh Supplement Retailer. February : 8.]

Citrus Pectin May Inhibit Metastasis of Prostate Cancer For patients with metastasized prostate cancer, the prognosis is cur­ The authors report that, to the best of their knowledge, "this is rently grim, as there is no known cure for it. Modified citrus pectin, the first report of an oral method to prevent spontaneous prostate a complex polysaccharide derived from citrus fruit, has been shown, metastasis." Further studies should focus on clarifying what con­ under special circumstances, to inhibit the ability of some melanoma centration of modified citrus pectin is needed to inhibit metastasis. cells to metastasize in the lungs of laboratory mice. The purpose of - Ginger Webb the present study was to determine if an oral dose of modified citrus [Pienta, K.J ., H. Naik, A. Akhtar, K. Yamazaki, T.S. Replogle, J. Lehr, T.L. pectin given to rats with prostate adenocarcinoma (glandular carci­ Donat, L. Tait, Y. Hogan, and A. Raz. March I, 1995. Inhibition of noma) could effectively inhibit its metastasis. Spontaneous Metastasis in a Rat Prostate Cancer Model by Oral Admin­ Four groups were formed with seven to eight rats per group. istration of Modified Citrus Pectin. Journal of the National Cancer In stiTute, Vol. 87, No.5, 348-353.] Experiments were performed twice. All the rats were injected with adenocarcinoma cells in their hind legs on day 0; starting on day 4, modified citrus pectin was given to the three experimental groups in their drinking water in concentrations of 0.0 I percent, 0.1 percent, and 1.0 percent. The experiment lasted 30 days. Of the control rats, 15 out of 16 had lung metastases (one control mouse had only lymph node metastases) on day 30 com­ pared to seven out of 14 in the 0.1 percent modified citrus pectin groups, and nine out of 16 in the 1.0 percent modified citrus pectin groups. The lungs of the rats in the 1.0 percent modified citrus pec­ tin group had significantly fewer metastatic colonies (1 ± I) than those of the control group (9±4). The results suggest that the effect of modified citrus pectin may be dependent on the concentration administered. Lemon, Citrus limon. Photo by David Baker for Herba/Gram.

HERBALGRAM No. 40 • 17 RESEARCH REVIEWS

Synergistic Action of Pygeum and Nettle Root Extracts in Prostate Disease

One of the theories about the cause of benign prostatic hyperplasia against 5 a-reductase and significantly more effective than either (BPH) suggests that the testosterone metabolite dihydrotestosterone against aromatase. This study supports the use of combinations of causes or furthers the progression of prostatic enlargement. This these two ingredients in the treatment of BPH. This is especially thinking is supported by the fact that men deficient in important because pygeum bark is both expensive and limited in dihydrotestosterone (DHT) do not experience prostatic growth, and supply, while nettle roots are easily produced on a large scale. - that treatment with prescription drugs which inhibit the production Rob McCaleb of DHT can decrease prostatic growth. An increase in the ratio of [Hartmann, R.W. , Mark, M. , and Soldati, F. 1996. Inhibition of 5 a-reduc­ estrogen to testosterone in elderly men indicates that estrogen may tase and aromatase by PHL-0080 I (Prostatonin®), a combination of PY also be involved in the development of BPH. I 02 (Pygeum africanum) and UR I 02 (Urtica dioica) extracts. Phytomedi­ In this study, Swiss researchers R. Hartmann et al. demon­ cine 3/2:121-128.] strate that extracts of pygeum bark (Pygeum africanum Hook F. , Rosaceae) and nettle root (Urtica dioica L., Urticaceae) partially blocked the action of two enzymes involved in the body's produc­ tion of DHT and estrogen. The in vitro (laboratory) study showed Andrographis vs. that both pygeum and nettle root extracts were effective in inhibit­ ing the two enzymes 5 a-reductase and aromatase and that a combi­ nation of the two plant extracts was significantly more effective than the Common Cold either extract individually in blocking aromatase activity. The Indian shrub Andrographis paniculata (Burm.) Nees, Nettle root extract was effective only at high concentrations, Acanthaceae has been used for more than 12 years in Nordic coun­ while pygeum extract showed "a much higher efficacy" at lower tries for reducing symptoms and duration of the common cold. In a doses. The combination of the two extracts (Prostatonin®, made by double-blind clinical study in 50 patients assessed by an extensive Pharmaton of Lugano, Switzerland) was as effective as pygeum diagnostic scheme, Andrographis produced dramatic positive results in three areas: Pygeum, l. Symptom relief. Fifty-five percent of those taking Pygeum Andrographis extract reported that their colds had been much easier africanum. than usual, while in the placebo group only 19 percent experienced Photo courtesy of lndena®, symptomatic improvement. Seattle, WA. 2. Days of sick leave. Those in the active treatment group averaged only 0.2 day of sick leave, while those in the placebo group averaged one day of sick leave during the five days of treatment. 3. Reduced duration of symptoms. After five days of treat­ ment, 75 percent ofthose in the active group were considered totally recovered, compared to fewer than 40 percent in the placebo group.

The researchers who conducted this Swedish trial conclude that Andrographis extract tablets "have positive effects on the treat­ ment of common cold." The authors also summarize other investi­ gations of Andrographis, including a Chinese study in which reduc­ tions in body temperature were observed in 70 of 84 patients. A controlled study conducted in Chile reported significant improve­ ments against symptoms of colds and sinusitis compared to placebo. Finally, in a study of 152 patients with sore throat (pharyngo-tonsil­ litis), Andrographis extract was as effective as acetaminophen in the treatment of all symptoms. Reports of side effects are rare with Andrographis, supporting the authors' conclusion that the plant is "very well suited as self-treatment in uncomplicated common colds." - Rob McCaleb [Melchior, J. , Palm, S. , and Wikman, G. 199611997. Controlled clinical study of standardized Andrographis paniculata extract in common cold­ a pilot trial. Phytomedicine 3/4: 314-318]

18 • HERBALGRAM No. 40 RESEARCH REVIEWS

Native Foods and Drugs of North America

Based on information gathered over 25 years of study and compiled Food and drug plants share some characteristics. Plants from in a large database, Daniel E. Moerman, Ph .D, of the University of the families Apiaceae, Rosaceae, Liliaceae, Lamiaceae (Labiatae) Michigan-Dearborn, compares the medicinal and food plants used and Solanaceae are widely used for both food and medicine. Food by native peoples of North America. There are 29 1 tribes and 3,895 and drug plants also show some differences. Even when the plants different species (4,397 discrete taxa) of plants represented in the come from the same family, they tend to involve different plant parts: database. Of all known North American vascular plant species, na­ roots tend to be used for drugs, fruits tend to be used as foods, and tive peoples ha ve used 11.8 percent for medicinal purposes (2,564 plant-tops are used as both food and drugs. Growth form (e.g., tree, of 21,64 1 species). grass, shrub, etc.) is related to plant use as well. Shrubs and trees The flora most used medicinally include plants from the fo l­ produce the greatest numbers of foods, although a disproportion­ lowing families: Asteraceae (Compositae), Rosaceae, Apiaceae ately high number of drugs come from shrubs and trees, as well as (Umbelliferae), Ranunculaceae, and Ericaceae. The flora most used from lianas, semi-shrubs, and vines. Finally, drug plants tend to be as foods include plants from the following families: Liliaceae (such perennials, while many food plants tend to be annuals. However, as species of Allium [onions, garlic, chives]); Rosaceae (particul arly only a tiny proportion of food plants in British Columbi a and Canada fruits and berries from the genera Rubus [blackberry, raspberry], are annuals, if any. Prunus [cherry, plum, peach], and Crataegus [hawthorn]); Ericaceae "The biggest puzzle remains," concl udes Dr. Moerman. "How (particularly from the genera Vaccinium [blueberry] and Arctosta­ did people learn of appropriate foods and medicines? This chal­ phylos [manzanita and bearberry/uva ursi]); Apiaceae; Cactaceae; lenging question remains very much open. While native orth and Fagaceae. Members of the family Solanaceae were used for American peoples used over 3,650 vascu lar species as medicines or both foods and medicines. The families Poaceae (Graminae) (the foods, that leaves nearly 18,000 other species which they did not grass family) and Fabaceae (Leguminosae) (the bean family) have use . Much challenging work remains to be done before we wi ll each been a source of many different foods, although their medici­ satisfactorily understand how our predecessors came to their remark­ nal use has been small. able understanding of the food and medicinal floras of this or any Studies in zoopharmacognosy, the term coined by Rodriguez other continent."- Ginger Webb and Wrangham in 1993 to denote the study of the use of plant medi­ [Moerman, Daniel E. 1996. An analysis of the food plants and drug plants cines by animals, have shown that the average number of food spe­ of native North America. Journal of Ethnophannaco/ogy, Vol. 52, 1-22.] cies eaten by a species of primate (not including humans) is about 43, and the number of species used as drugs between one and three. Left: Green-leaf manzanita, Arctostaphylos patula; right: The average number of food species eaten by the people of several Blackberry, Rubus fruticosus. Photos © 1996 Steven Foster. dozen native tribes is comparable, at about 58.5. When it comes to drug plants, however, native peoples have used a much hi gher num­ ber, often about 300. Of the total number of vascular plant species used, 19 percent are used on ly for food , 29 percent are used for both food and medicine, and 45 percent are used on ly as medicine.

HERBALGRAM No. 40 • 19 RESEARCH REVIEWS

Plants with Antidiabetic Activity The ethnopharmacological use of herbal remedies for the treatment who were administered M. charantia fruit juice. The hypoglycemic of diabetes mellitus is an area of study ripe with potential as a start­ activity of alkaloids isolated from the Madagascar periwinkle ing point in the development of alternative, inexpensive therapies ( Catharanthus rose us (L.) G. Don f., Apocynaceae) have been stud­ for treating the disease. There are over 30 million people today ied pharmacologically since the 1920s, and a remedy derived fro m suffering from one form of diabetes or another, and the numbers are the plant has been marketed in England under the proprietary name increasing in rural and poor populations throughout the world. There Vinculin as a treatment for diabetes. Sulfur compounds in onion are three main types of the disease: insulin-dependent diabetes mel­ (Allium cepa L., Liliaceae) and garlic (A. sativum L.) are believed to litus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), exert hypoglycemic activity by competing with insulin. The chro­ and malnutrition-related diabetes mellitus (MRDM), which affects mium, manganese and magnesium salts present in the saltbush youn g people in poor tropical countries and is linked to a hi story of (A triplex halimus L., Chenopodiaceae) are believed to prevent dia­ nutritional deficiency. Modern therapies are far too costly to be betes from occurring in sand rats who feed regularly on the plant practical for the majority of diabetes sufferers. Researchers pub­ and who have a genetic predisposition to diabetes. li shed an extensive review of plants with reported antidiabetic ac­ Seeds from a number of plants in the Fabaceae are used tradi­ tivity in order to provide the preliminary information needed to tionally to treat diabetes, including fenugreek (Trigonella foenum­ design research whose goal it is to develop "indigenous, renewable, graecum L., Fabaceae) whi ch contains a number of hypoglycemic medicinal plant resources as practical cost-efficient alternatives." principles. In addition, the dietary effects of these plants are impor­ Over I ,200 organisms (representing 725 genera in 183 fami­ tant. Clinical studies of hi gh legume diets exhibit improvement in lies) have been used or experimented with ethnopharmacologicall y blood glucose control, and the complex carbohydrates in beans are in treating diabetes, or the obvious symptoms of the disease. The more slowly digested than other starches. Other widely used plants plants which have been used represent a wide range of families. Of with promise include: Anacardium occidentale L., Anacardiaceae; these, 127 species are found in the Fabaceae (pea family), 98 in the Syzygium cumini, L., Skeels, Myrtaceae; Eucalyptus globulus Labill., Asteraceae (aster or daisy family), 36 in the Lamiaceae (mint fam­ Myrtaceae (eucalyptus); Lupinus albus L. , Fabaceae; Aloe vera L., ily), 35 in the Liliaceae (lily family), 30 in the Poaceae (grass fam­ Liliaceae; Tecoma stans Juss., Bignoniaceae; Urtica dioica L., ily), and 30 in the Euphorbiaceae (spurge fami ly). Screening these Urticaceae (stinging nettle); Taraxacum officinale Weber, Asteraceae plants for hypoglycemic (blood sugar lowering) activity has shown (dandeli on); Kyllinga monocephala Rottb., Cyperaceae; Phyllanthus that 8 1% yield positive results. This figure reflects the "great vari­ emblica L. and P niruri L., Euphorbiaceae; Azadirachta indica A. ety of possible active constituents and mechanisms of action," and Juss. Meliaceae (neem); Morus alba L., Moraceae; Poterium illustrates the excellent potential for discovering new sources of an­ ancistroides Desf., Rosaceae; Daucus carota L., Apiaceae (wild tidiabetic drugs. Promising leads reflecting this wide range of an­ carrot); Blighia sap ida Konig, Sapindaceae (akee); Galega officina/is tidiabetic constituents and mechanisms of hypoglycemic activity are L., Fabaceae (goat's rue); Ganoderma lucidum (W. Curt.:Fr.) Karst., being studied. Ganodermataceae (reishi); and Panax ginseng C. A. Meyer, Arali­ For example, the peptides and terpenoids from bitter gourd aceae (Asian ginseng). -Ginger Webb (Momordica charantia L. , Cucurbitaceae), perhaps the most widely [Maries, R.J., and N.R. Farnsworth. 1995. Antidiabetic plants and their used traditional antidi abetic remedy, are believed to be responsible active constituents. Phytomedicine, Vol. 2(2), 137-189.] for the plant's hypoglycemic properties. One clinical trial showed improved glucose tolerance in 73 percent of patients with NIDDM Left to right: Fenugreek, Trigonella foenum-graecum; Sweet Annie, Artemisia annua; Saltbush, Atriplex spp.; Madagascar periwinkle, Catharanthus rose us . All photos © 1996 Steven Foster

20 • HERBALGRAM No. 40 RESEARCH REVIEWS

Camptothecin and Taxol- Natural Anti-Cancer Agents Camptothecin and taxol are plant-derived secondary metabolites and fruit of the tree were initially screened for antitumor activi ty whose medicinal and therapeutic activities have been uncovered under a collaborative program between CI and the U.S. Depart­ through scientific research. Camptothecin (CPT) is derived from ment of Agriculture (US DA). Thi s sc reen ing showed that samples the stembark of Camptotheca acuminata Decne. , yssaceae, a tree of the stembark exerted cytotoxic activity. At RTI , the secondary native to China. Under the leadership of M.E. Wall and with sup­ metabolite named taxol was isolated through bioactivity-guided frac­ port from the ational Cancer Institute (NCI), a natural products ti onation. Taxol has been used in clinical settings since 1988 for the group was established to study C. acuminata. treatment of women wi th advanced ovarian cancer. There have been The researchers isolated CPT as the biologically active com­ numerous cases of parti al or complete remission. The drug and an pound in C. acuminata, and extensive animal antitumor studies were analog, taxotere, have also been reported to be effective in cases of conducted on CPT and its analogs. CPT sodium salt, which is, in breast, lung, and prostate cancer. Studies have shown that taxol contrast to CPT, water-soluble and therefore easily ad ministered in­ exerts its antitumor activity by binding to tubulin, the principle pro­ travenously, was chosen by NCI for clinical trials in the early 1970s. tein in vo lved in mitosis, thereby inhibiting ce ll division. CPT sodium salt is only 10 percent as active as CPT. The trial s, Producing taxol from the stem bark of the Pacific yew, a non­ however, were terminated due to observation of severe bladder tox­ renewable source, led initiall y to shortages of the drug and decima­ icity. In China, positive results were reported: up to I ,000 patients tion of wi ld yew populations. In order to obtain adequate quantities, with no prior antitumor treatment were treated and positive results measures have since been taken to produce taxol from other Taxus were reported in gastric cancer, intestinal cancer, head and neck tu­ species, and to produce synthetic or semisynthetic taxol. The needles mors, and bladder carcinoma. Results were more promising in China of the European yew (T. baccata) and otherTax us species have been because the previously treated American patients had drug-resistant found to yield intermediate compounds called baccatins, which are form s of cancer. readil y converted to taxol and taxotere. These needles are consid­ In 1985 it was discovered that CPT inhibited topoisomerase I ered a renewable source of these drugs, since harvesting the needles (T-I), an enzyme which has been implicated in various DNA trans­ does not harm the tree in the way that harvesting the stem bark does. actions including replication, transcription, and recombination. Ta.xomyces andreanae, a fungus discovered growing on the bark of Pharmacia & Upjohn's irinotecan (CPT- II , Camptosar™) has also a single Pacific yew tree in an undisturbed growth forest in Mon­ been approved by the FDA. tana, has also been found to be a renewable source of these drugs: Topoisomerase I is found in all ce ll s, healthy or cancerous. the fun gus not onl y contains taxol , but actually produces it. -Gin­ One form ofT-I inhibition has some selectivity for cancer cells only ger Webb because cancer cells are dividing much more rapidly than most nor­ [Wall , M. E. and M. C. Wani. 1996. Camptothecin and taxol: from di scov­ mal cells (except gut epithelium = nausea/vomiting/diarrhea, hair ery to clinic. l ou mal of Ethnopharmacology, Vol. 51 , 239-254. follicles = hair loss in treatment), and so cancer cells are affected Webb. G. , Fungus and Taxol, Herba/Gram 38, 19.] more rapidly. [Topo I is the conventional abbreviation for Chips are sawed for topoisomerase I, T-1 is a neologism. It is certainly found in cancer HPLC testing from a cells but also in any cell which is replicating ... the basis for action is 28-foot stem of that rapidly growing cells will be affected the most.-John Beutler, Camptotheca Ph.D.] acuminata, planted CPT and some of its analogs are currently in clinical trial, and in 1993. Photo taken are showing promise against a variety of tumors which ha ve not June 1997, courtesy yielded to other treatments. One of the analogs, topotecan, devel­ of XyloMed Research oped by SmithKiine Beecham, has recently been approved by the Inc. , Monroe, LA, a FDA for general use in the treatment of ovarian cancer. Pharmacia non-profit & Upjohn's Camptosar™ has also been approved by the FDA. organization spec ializing in Taxol is isolated from the Pacific yew tree (Ta.xus brevifolia C. acuminata. Nutt., Taxaceae) and was discovered at RTI in 1966. Before the study of the Pacific yew tree was assigned to RTI, bark, twigs, leaves,

ERRATA In HerbalGram No. 39 in the Research Review "Anti-oxidant Effects of Chamomile Compounds," the materi al citing the original author was inadvertently omitted. The citation should read [Viola H., de Stein, ML, C. Wolfman, et al. Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptor-ligand with anxiolytic effects. Planta Medica 1995 ; 61 :2 13-6.]

HERBALGRAM No. 40 • 21 Herb Research Foundation's Herb Information Packet Series Has What You Need

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HERB RESEARCH FouNDATION

100 7 Pearl Street, Suite 200 Boulder, CO 80302 PLANT PATENTS

By Karen Dean

CINNAMON CIWUJIA POLYGONUM Method for inhibiting growth of Method to improve performance during ex ­ Composition and method for treating hyper­ Helicobacter pylori. Invented by Itzhak ercise using the ciwujia plant. Invented by glycemia utili zing an extract of Po/ygonum Neeman, Mina Tabak, and Robert Armon. Robert Portman. Assigned to Pac ifi cHealth multiflorum. In vented by an-Zheng Cheng Assigned to Technion Research & Develop­ Laboratori es, Inc ., Woodbridge, NJ. U.S . and Barbara Stoecker. Assignee The Board ment Foundation Ltd ., Technion City, Israel. Patent 5,585, I 0 I issued December 17, 1996. of Regents of Okl ahoma State Un iversity, U.S. Patent 5,560,9 12 issued October I, PacificHealth is commercializing thi s Stillwater, OK. U.S. Patent 5,531 ,99 1 issued 1996. patent, which covers the use of a daily dos­ Jul y 2, 1996. Covers use of an organic extract, or age of between 200 mg and 1600 mg of an utrition researchers at Oklahoma chemical constituents (preferably aqueous extract of the root and rhi zome of State Uni versity have identified three frac­ cinnamaldehyde and methoxycinnam­ ciwujia (Eleutherococcus senticosus (Rupr. tions of extracts of the Chinese herb aldehyde), of the plant cinnamon & Maxim.) Maxim. , Araliaceae; syn. Polygonum multiflorum Thunb., Polygo­ (Cinnamomum zeylanicum Breyn., Acanthopanax senticosus (Rupr. & Maxim.), naceae as potentiating insulin activi ty in fat Lauraceae) to prepare a pharmaceutical com­ Harms, to enhance stamina and physical per­ cell assays and lowering blood glucose lev­ position that inhibits the growth and the ure­ formance during exercise and to enh ance els in animal studies. The laboratory in ves­ ase activity of the Helicobacter pylori bac­ recovery of human beings after exercising. tigations of thi s herb, whi ch Chinese herbal terium, which has been identified as a lead­ Ciwujia (pronounced "su wah ja," accord­ medicine uses principall y to treat poor sleep, ing cause of gastric ulcers. The extract may ing to the patent) is an herb native to north­ demonstrate unexpected hypog lycemic be used either as a drink, with or without east China, where it has a long hi story of use blood-glucose-lowering activity. Polygonum additional flavorin g ingredients, or trans­ in Traditional Chinese Medicine as a fatigue is sold in the U .S. as a traditional Chinese formed into a capsule. The invention also fi ghter and immune booster, and as an aid to herb by its Chinese name Ho Shou Wu. How­ relates to an in vitro method of determining the performance of mountain climbers. ever, it is popularly known in the U.S. mar­ the inhibition of urease ac tivity of H. py­ PacificHealth's fl agship product, a dietary ket as "Fo Ti ." lori, using an organic extract or chemical supplement, contains a pure standardized constituents of the plant. extract of the plant, which the company pro­ motes as "a natural dietary supplement that when taken as part of a normal workout regi­ men can increase fat metabolism and im­ PIPERINE prove workout performance." Use of piperine to increase the bioavailability The company offers the resu lts of a of nutritional compounds. In ve nted by number of laboratory animal and hum an Muhammed Majeed, Vladimir Badmaev, and studies, demonstrating that ciwujia improves R. Rajendran . Assigned to Sabinsa Corpo­ athletic endurance and recovery from exer­ ration, Piscataway, NJ. U.S. Patent 5,536,506 cise-induced fatigue. It appears that the issued July 16, 1996. company's exclusivity over ciwujia deri ves Oral, topical, or parenteral administra­ principally from the research it has sponsored. tion of the alkaloid piperine, which is ex­ It is ironic that ciwujia's long hi story tracted from the fruit of Piper genus plants, of use by Chinese herbal medical practitio­ improves the gastrointestinal absorption and ners, to improve physical endurance, mi ght, systemic utilization of nutrients and nutri­ in fact, weaken the strength of the patent on tional supplements. Sabinsa has patented not the plant. The patent-holder's exclusivity onl y the use of piperine to improve over ciwujia may owe more to the inform a­ bioavailability of nutritional compounds, but tion resulting from research the company about a new process for the extraction and conducted or sponsored than to any discov­ purification of the alkaloid from the fruit. ery of a novel or previously unexpected prop­ The company, a natural products and nutri­ erty of the plant, or development of a spe­ ti onal ingredient manufacturer, seeks many cialized and hi ghl y proprietary processing of its product leads from plants with a long technology. hi story of safe and well-documented use in Ho Shou Wu, Polygonum multiflorum. traditional Indian Ayurvedic medicine. Photo ©1997 Steven Foster.

HERBALGRAM No. 40 • 23 LEGAL AND REGULATORY

FDA Publishes Proposed Regulations for Good Manufacturing Practices for Dietary Supplements

by Rob McCaleb

On February 6, 1997, the Food and Drug comments favorable to its own views that comments on the proposed GMPs. Administration (FDA) published proposed dietary supplements represent a public health The GMPs require production and pro­ regulations for good manufacturing practices risk beyond that of conventional foods. It cess controls, including master production (GMPs) for dietary supplements. The de­ appears that FDA might be suggesting that and control records "as appropriate." These velopment and implementation of new supplement manufacturers adhere to a higher are fairly standard suggestions requiring GMPs were mandated by Section 9 of the standard than that required of OTC drug complete li sting and name, weight, and mea­ Dietary Supplement Health and Education manufacturers. sure of ingredients used in each product. Act of 1994 (OSHEA), which called for cre­ The first question the agency asks in Additionally, however, they suggest a "state­ ation of new GMPs based on food GMPs, its proposed rules is whether there is a need ment of theoretical weight or measure" of not drug GMPs. for regulations covering GMPs for dietary an ingredient at the conclusion of manufac­ In November 1995, four trade associa­ supplements. The purpose of the proposed ture, and require a statement of actual yield tions in the dietary supplement industry rules is to solicit comments on that question at the conclusion of manufacture. This is an jointly prepared and submitted a set of GMP and on the proposed rules by parties other easier task for vitamins than for herbs. As in recommendations (Blumenthal, 1996). The than the industry trade associations who sub­ many sections of the GMPs, these are re­ associations were the American Herbal Prod­ mitted the "industry draft." The agency is quired "as appropriate," leaving some lati­ ucts Association (AHPA), Council for Re­ responsible for establishing rules that "will tude in their application where they may be sponsible Nutrition (CRN), National Nutri­ insure that dietary supplements are produced impractical. tional Foods Association (NNFA), and Utah under conditions that will result in a safe The FDA proposal would increase Natural Products Alliance (UNPA). Prior to and properly labeled product, but that does record-keeping requirements, especially for the passage of OSHEA, and at present, the not impose any unnecessary burden on the smaller companies. For example, it requires dietary supplement industry is required only industry." written procedures for receiving, handling, to adhere to good manufacturing practices The industry draft contains many stan­ sampling, testing, and approving of raw ma­ applicable to foods, since supplements have dard features of good manufacturing prac­ terials, raw material lot number tracing, and always been regulated as foods. GMPs for tices already in place for foods. On the sub­ written procedures for testing, processing, foods address basic sanitation issues and cer­ ject of quality control and laboratory opera­ and other record-keeping details. In the lab tain requirements for facilities and person­ tions, the proposal would require that there testing section, it would require testing for nel. When OSHEA defined dietary supple­ be a quality control unit, and describes the filth, insect infestation and other contami­ ments as a distinct category for regulation, it responsibility and authority of that unit. If nants, or a guarantee or certificate of analy­ included a section under which the Secre­ any dietary ingredient or supplement bears sis from the supplier. Microbiological ex­ tary of Health and Human Services could pre­ an expiration date, it must be supported by amination is required where appropriate, as scribe GMPs for dietary supplements. It was data and rationale for that date. Accelerated is aflatoxin testing for materials susceptible expected that these would be stricter than stability studies are allowed, but product to such contamination. food GMPs but less strict than those for shelf life must be confirmed on the basis of In Section 7(iv) the GMPs require each drugs. The industry submission includes "real time studies" on products stored under lot of raw material to undergo at least one some points which may be problematic for labeled storage conditions. test to verify its identity, which may include smaller companies, and, in fact, may be dif­ This seems to be a reasonable sugges­ chemical and laboratory tests, gross organo­ ficult to implement for a company of any tion, but could be problematic for some leptic analysis, microscopic identification, or size. herbal supplements because the active com­ analysis of constituent markers. If a manu­ The FDA, in responding to the pounds have not been identified. In many facturer accepts a certificate of analysis in­ industry's submission, states that it is "an cases, it is simply not known how to estab­ stead of independently testing the product, extremely useful starting point," then asks lish analytically when an herb has ceased to the manufacturer must establish the reliabil­ nine specific questions the agency thinks are be effective. According to OSHEA, no ity of the supplier's analyses. not addressed. In some of these questions, GMPs can be imposed if analytical method­ The GMPs require stock rotation to use the agency editorializes a bit about dietary ology is unavailable. It is very likely that the oldest approved stock first, with an al­ supplements, and appears to be soliciting this point wi ll be emphasized in industry lowance for deviation if "temporary and ap-

24 • HERBALGRAM No. 40 LEGAL AND REGULATORY

propriate." It requires retesting of materials level-i.e., below the DAL. The American will likely be required, but certificates from after a specified time in storage. The GMPs Spice Trade Association (ASTA ) has worked ingredient suppliers could be adequate if their go on to describe details of manufacturing with FDA over th e years to establi sh DALs program of botanical testing of raw mate ri al operations to assure that reasonable precau­ for common spices. However, there are few is adequate. ti ons are taken to avoid contamination. DALs set fo r non-spice botanicals. Question 3: FDA requests information Economic issues are addressed in the The agency betrays its bias in charac­ on contam ination by pesticides and other proposed rules as the agency "seeks infor­ teri zing supplements as a substanti al source impurities, and again editorializes that "many mation on how closely the current practices of exposure to natural defects. Since indi­ ingredients used in dietary supplements do of manufacturers of dietary supplements con­ vidual supplements are consumed in quanti­ not have a hi story of food use in the United form to the industry submi ss ion and how ties typicall y less than 2 grams per day, they States and thus the potential for co ntamina­ costly it would be to bring those practices represent much less exposure to natural de­ tion with mi croorganisms or filth is un­ into conformity." The agency is looking for fects than those occurring in conven ti onal known." There is, of course, no reason to comments from small and large businesses. foods which are consumed in ounce or pou nd suspect that herbs are any more li kely to be quantities as a part of the daily di et. The so contaminated than any other raw agricul­ THE AGENCY ASKS NINE agency presents no data to support its con­ tu ral com modity. Further, these products are QUESTIONS IN ITS REQUEST FOR tention that supplements would increase the not new to the American market, and thus COMMENTS. ex posure to defects and ignores the fac t that do have a long history of food use in the U.S . Question I: The FDA as ks if there is a need botanicals consumed as spices may be taken Question 4: The FDA suggests that it to develop defect action levels (DALs) for in substantiall y hi gher quantities in food than is possible that a company wi ll develop ad­ dietary supplement ingredients. The agency in dietary supplements (for example, a serv­ eq uate standard operating procedures, but comments that there are established DALs ing of basi l pesto often contains more herb such procedures wi ll not be followed. The for many food ingredients, including botani­ than would fit in a dozen capsules). The herb agency asks whether there should be add i­ cals, which it characterizes as "trace ingre­ industry is beginning to request from its tional controls to document that procedures dients in foods." The proposal states, "the members data on natural defects in botani­ prescribed are followed on a day-to-day ba­ use of a botani cal in a dietary supplement cals with the goal of collecting enough data sis. This appears to be a "dig" at th e di etary may result in a much greater exposure to the points to present meaningful data for th e es­ supplement industry, suggesting that some botanical ingredient for consumers because tablishment of DALs. This cou ld be an es­ add itional layer of documentati on is required the dietary supplement will be consumed in pecially troublesome area for those compa­ for the supplement industry which is not re­ greater amounts than if the ingredient was nies who import raw botanicals as opposed quired of other food companies. [sic] in a food as a spice or flavorin g agent." to those using extrac ts. Questi on 5: FDA asks for comments The FDA concludes that it wou ld not be ap­ Question 2: The age ncy requests com­ on whether reports of illness or injury should propriate to apply existing DALs to dietary ments on testing requi rements to provide be evaluated by competent medical authori­ supplements and asks for help developing positive identification of ingredients, particu­ ties. The Agency states, "the presence of DALs for dietary supplements. larl y plant materials, and suggests th at pharmacologica ll y active substances in these Comment: Defect Action Levels are mi sidentification may present a significant products distinguishes them from most other based on the concept of "unavoidable natu­ public health and economic concern . The food ,"and suggests serious injury or illness ral defects in foods. " Since herbs and spices industry will no doubt comment that appro­ potential may require evaluati on by medical are dried agricultural products, such defects priate testing of identity varies accord ing to professionals of reported adverse reactions. include insect fragments, insect and/or ro­ the nature of the spec ific product and that in Comment: This is a most problemati c dent excreta, hairs, and so on. A DAL is that many cases, macroscopic or microscopic suggestion by the FDA. Manufacturers of level of extraneous matter that exceeds a tol­ examination, combined with organolepti c all types of products receive reports of ad­ erable amount and which then requires an (i. e., sensory evaluati on of material by sight, verse reactions, many of whi ch are never "action"-i.e. recleaning or other process­ taste, and/or smell ) testing is adequate to as­ conclusively linked to the company's prod­ ing, re-exporting, or destruction of the ma­ sure the identity of many botanical raw ma­ ucts. Since manufac turers do not have ac­ teri al if it cannot be cleaned to a satisfactory terials. For extracts, some chemical testing cess to a customer's medical records or hi s-

HERBALGRAM No. 40 • 25 LEGAL AND REGULATORY

tory, the type of follow-up which the agency regulation. that the industry includes a spectrum of com­ is suggesting may not be possible. The pres­ Question 7: FDA asks about computer panies, some of which manufacture and oth­ ence of pharmacologically active substances software and equipment used to direct and ers of which simply distribute supplements has nothing to do with good manufacturing monitor manufacturing. or their ingredients. practices, and post-marketing surveillance is Question 8: FDA asks whether a regu­ not a GMP issue, unless it relates to defec­ lation based on Hazard Analysis and Criti­ Conclusions: The proposed GMPs tive product resulting from poor manufac­ cal Control Points (HACCP) principles submitted by the industry associations ap­ turing practices. would be more appropriate than the more pear thorough and adequate, and in fact, in Question 6: The agency asks whether standard system as outlined by the industry some cases include requirements which may manufacturers should establish procedures to proposal. HACCP has rarely been required be more difficult to meet than the industry evaluate potential safety concerns with di­ of any food products and would likely in­ knows or intends. The FDA's nine questions etary ingredients. In this section, the FDA is crease the cost of complying with GMPs. apparently seek to expand the GMP require­ asking whether good manufacturing practice The agency says, "principles of HACCP may ments into areas which would be more bur­ records should include an evaluation and provide a more flexible and less burdensome densome for the industry and in some cases, documentation of safety, and asks what type regulatory framework for manufacturers and difficult or impossible to achieve. Also as of records would be adequate to document di stributors than the approach set out in the noted, some are not GMP issues at all, but "that such an evaluation had occurred." industry submission." seem to be aimed at reopening the debate Comment: This section has no pl ace Comment: HACCP is not applicable about the burden of proof on safety issues in a Good Manufacturing Practices proposal to or appropriate for dietary supplements and expanding GMPs to include post-mar­ and has been the source of considerable con­ because it attempts to identify points at which keting surveillance of products to monitor cern in the industry. Companies are respon­ contaminants could be introduced into the adverse reactions. sible for marketing safe products, and the product or safety could be compromised Comment Extension: The dietary substantiation of the inherent safety of an through manufacturing errors. The most supplement industry had requested an exten­ ingredient is not a typical GMP issue. This typical examples are food products which sion to August in order to organize some appears to be another reaction by the agency have identifiable points at which microbial meetings and discuss the various issues to its loss of food additive regulations as a contamination could be an issue. In botani­ raised by the proposed regulations. The Non­ way of chall enging companies to substanti­ cal products especially, the most important prescription Drug Manufacturers' Associa­ ate the safety of their products. OSHEA critical control points are prior to the receipt tion (NOMA) and CRN had also asked clearly di sallows the FDA from regul ating of raw materials by a company. Most manu­ for an additional 90 days. However, FDA herbs as "food additives" which are approved facturing steps taken to produce a upplement granted only a 30-day extension to for safety by FDA before being allowed into from an incoming raw material are processes June 6th. 0 the marketplace. Under OSHEA the agency which would not be expected to introduce [Sources: Blumenthal, M. 1996. FDA Accepts now has the burden of proof to support its contamination to the product. In this author's Supplement Industry GMP Proposa l. Herbal­ removal of products from the market if it opinion, the GMPs as proposed by industry Gram 38: 27-28. FDA. 1997. Current Good deems they pose a health risk. Perhaps the are more appropriate than HACCP. Manufacturing Practice in Manufacturing, Packing, or Holding Dietary Supplements; Pro­ FDA believes it can slip the burden of proof Question 9: The agency asks whether posed Rule. Federal Regista Vol. 62, No. back to the industry in this proposed GMP there should be distinctive requirements for 25, Feb. 6: 5700-9.] each segment of the industry, noting correctly FDA Proposes Warnings and Dose Limits on Ephedra Government Proposal Comes Three Years After Industry Warning

by Mark Blumenthal

The Food and Drug Administration etary supplements containing the herb. The in previous issues 34- 39 of HerbalGram). (FDA) has issued its long-awaited proposed 40 -page proposal was published in the Fed­ Ephedra contains the alkaloids ephedrine and regulations on the controversial herb rna eral Register on June 4 (FDA, 1997). pseudoephedrine which have been employed huang, aka ephedra (Ephedra sinica Stapf., The FDA action comes after several in both prescription and nonprescription Ephedraceae). The new rules contain a pro­ years of concern about the safety of prod­ medications for bronchodilator and decon­ posed warning and dose limitations on di- ucts containing the herb (please see articles gestant activity. Ephedra also contains at

26 • HERBALGRAM No. 40 LEGAL AND REGULATORY

least four other related alkaloids. cerns about the potential adverse effects of ditive" in such cases and products would be The proposed regulations include the using OTC drugs with ephedrine, pseu­ deemed ad ulterated and unsafe. followin g provisions: doephedrine, and caffeine beverages. It is 7. The proposed regul ations wi ll ban l. The maximum allowable dosage for hi ghl y likel y th at many people use OTC the use of ephedra in so-call ed "street drug total ephedrine alkaloids is proposed to be 8 drugs and caffeine simultaneously. "Nobody knockoffs" - products whose intended use mg per unit dose with a maximum dail y dos­ is more at risk from the herbs cola and is to give some type of"high" and are clearl y age of 24 mg. This is lower than what many mahuang than they are from Primatene® and not part of the dietary use of botanical di­ members of the herb industry had hoped for espresso," says Rob McCaleb, President of etary supplements to promote health. This and is considerably lower than the 25 mg of HRF and member of th e Commission on Di­ refers to products such as "Herbal Ecstacy," alkaloid presently allowed for the alkaloid etary Supplement Labels (McCaleb, 1997). "Cloud 9," and "Ultimate Xphoria" wh ich pseudoephedrine in OTC drugs. (FDA is 4. Products containing ephedra will not rece ived widespread media attention in the currently considering banning the use of be allowed to make claims for body building spring of 1996 after the death of a 20-year­ ephedrine from OTC drugs.) or weight loss, two areas of use that have old college student assocated with the use of 2. The maximum all owable duration driven sales of ephedra-containing herb prod­ one of these products (Blumenthal, 1996) . of use will be 7 day s. This is a major con­ ucts in the last decade. The process by whi ch the FDA pro­ cern to tho e companies who market prod­ 5. Multiple warnings must be incl uded duced the proposed regul ati ons was charac­ ucts intended to enhance athletic perfor­ on the label , including the fo ll owi ng: "Tak­ terized by considerable commu ni cation and mance and for weight loss purposes. By lim­ ing more than the recommended serving may cooperation with industry groups in whi ch iting the period of use to one week, the only res ult in heart attack, stroke, se izure, or industry worked with the agency to develop products that would remain on the market death ." "Do not use thi s product for more meaningful and reasonable regulations. FDA wou ld be those intended for short-term use, than 7 days." Additionall y, a li st of also convened two advisory panel meetings e.g., colds, decongestion, etc. contraindications similar to those already re­ to soli cit input from industry members and 3. Combination products containing quired for OTC drugs containing ephedrine sc ientists before formulating its proposed caffei ne or caffeine-containing herbs will not and pseudoephedrine will be required, e.g., policy. The deadline for public comment be allowed. This is based on the large num­ hypertension, heart disease, diabetes, thyroid on the proposed regulations is August 19, ber of adverse reactions that FDA has re­ disease, difficult urination due to enlarged 1997.0 ceived associated with products containing prostate, pregnancy, nursing, etc. (This has combinations of herbs with caffeine, e.g, cola already been part of the industry's self- im­ REFERENCES nut (Cola spp.) or guarana (Paullinia cupana posed labeling poli cy for three years.) Blumenthal. M. 1996. The Agony of the Ecstacy. Herba/Gram 37:20-24. 32. 49. Kunth, Sapindaceae). This rai ses a question 6. Conve nti onal foods: The use of Food and Drug Administration. 1997. Dietary Supplement s as to whether there is an actual synergy be­ ephedra as an ingredient in conve nti onal Containing Ephedrine Alkaloids: Proposed Rul e. Fed­ tween caffeine and ephedrine alkaloids (they eral Register Vol. 62. No. 107. June 4: 30678-307 17. food s will not be all owed; the herb ephedra McCaleb. R.M. 1997. Personal communicati on. June 9. are both CNS stimulants). It also raises con- will be considered an "unapproved food ad-

LAPD Issues Kava Retraction

The Los Angeles Police Department has is­ dustrial Laboratories in Denver. The analy­ despite the fact that LAPD was aware of both sued a retraction of a portion of its press re­ sis found no traces of kava pyrones, natu­ ABC's and FDA's results, and, despite at­ lease in earl y January which implicated the rally occurring chemical compounds charac­ tempts by various persons in the kava indus­ herb kava kava (Piper methysticum Forst., teristic of kava. try to clear the adverse publicity, LAPD did Piperaceae) in the hospitalization of New Almost two months passed between not retract its initial release. Year's Eve concertgoers who ingested a the time that ABC notified LAPD (January FDA has so far refused to publish any product called "fX." As reported in Herbal­ 14) that the product did not contain kava release or report indicating that kava was not Gram 39, the American Botanical Council and LAPD's second press release (March 6 , involved. According to William Dailey, at­ broke the story to the Los Angeles Tim es that backdated by LAPD to February 27). torney for Kava Kompani of Seattle, Wash­ the toxic fX product did not contain any kava, In January LAPD had ac kn owledged ington, this refusal is "a slap in the face for despite news reports based on the LAPD to ABC that ABC's lab findings were con­ the entire di etary food supplement industry. " press release. ABC had obtained several vi­ sistent with the analysis conducted by the FDA gives as the reason for thi s nondi sclo­ als of the product and had them tested at In- Food and Drug Admini stration . However, sure an ongo in g investigation into th e event.D HERBALGRAM No. 40 • 27 LEGAL AND REGULATORY

Industry Alert: Plantain Adulterated with Digitalis

by Mark Blumenthal

In May and June the FDA and herb an ac ute angle), is di ffe rent than plantain sold in bul k in retail stores. It also clarified industry learn ed that vari ous lots of of the because the leaves of the first-year growth th at consumers should not confuse the herb herb plantain had been adulterated with po­ of the perennial vari ety grow fro m a com­ plantain with the fruit of the same name, tentiall y toxic woo ll y foxg love. FDA re­ mon base, industry experts co nj ecture that Musa X paradisiaca L., a member of the ceived reports that a Massachusetts wo man some inexperienced herb coll ectors in Eu­ banana famil y Musaceae. The FDA release had been hospi tali zed after having consumed rope may confuse the two pl ants, although is avail able on the agency's home page on a produ ct call ed "Chomper," part of the the distincti on shoul d be ev ident. Symptoms the World Wide Web at thi s address: http:/ "Cleanse Thyself ' line produced by the Arise of digitali s ingesti on may include nausea, w w w. f d a. gov /b b s/to p ics / N E W Sf and Shine company of Mount Shas ta, Ca li ­ vo miting, di zziness, headac he, confusion, NEW00570.html fo rni a. The company has voluntari ly recalled hypotension, vision di sturbances, and abnor­ On June 13 the Herb Research Foun­ suspected batches of the produ ct (HR F, mal heart rate and rhythm (FDA, 1997b). dati on issued a release summari zing the 1997). This incident has sin ce become Unfortun ately, the Chomper incident FDA's release and emphasizing th at indus­ known as the "Chomper issue. " Chomper is does not appear to be an isolated case. In its try assoc iati ons were "strongly advising all promoted as an "herb al laxati ve " and research, the agency has fo und that the adul­ di stributors and manufac turers to stop dis­ "cleansi ng agent," according to an FDA press terated materi al has been sold for up to a year tributing pl antain and pl antain-containing advisory on May 14 which warns consum­ by several distributors to manufacturers and products until they can be tested .... " (HRF, ers of the issue. The advisory said th at a retailers. On June II the agency convened a 1997a). On June 16 HRF provided industry young wo man using the product suffered video teleconfe rence with vari ous members groups with the name of a qualified micros­ from "abnormal heart rate with heartblock" of the herb and di etary supplement industries copist who was able to analyze dry powdered (FDA, 1997a). -American Herbal Products Associati on samples of product to determine identity of Plantain (Plantago major L. and re­ (AHPA), Co uncil fo r Responsible Nutrition pl antain and/or di gitali s. lated species of th e Plantag inaceae) is a low­ (CRN), and Nati onal Nutri ti onal Foods As­ FDA research indicates that at least growing plant th at has been used tradi tion­ sociation ( NFA)-plus ABC and HRF, in three shipments totalling approxim ately all y in England and Europe as a foo d and a good-faith attempt to communicate its fi nd­ 3,000 pounds of the mislabeled materi al were medicine. It is frequently employed in vari ­ ings and concerns and to request input fro m shi pped from Germany to Herbarium, an ous diuretic, laxati ve, and weight loss herbal the herbal movement. FDA sc ienti st Will­ importer/di stributor in Kenosha, Wisconsin, fo rmulas. The leaf or its extracts are also iam Obermeyer presented mi croscopic and during the past year. Most of the materi al used externall y in the fo rm of salve and oint­ chemical data showing di stincti ons between seems to have been imported and di stributed ments . Its safety is we ll known. Planta in the two plants. He had fo und lanatosides in through this company. According to AHPA has leaves with parallel ve in s; the leaves samples of "plantain" thus confirming the President Jeff Morri sson, FDA is attempting grow fro m a common base. adulaterati on. to determ ine whether the mi slabeled mate­ Woo ll y foxg love (Digitalis lanata On that same day, ABC released a brief ri al can be traced to more than one European Ehrh ., Scrophul ariaceae) is native to south­ press release advising industry members of ex porter (Morrisson, 1997). ern Europe, especially along the Danube the problem. ABC recommended "voluntary Ironi call y, the Chomper issue comes (Morton, 1977). It is cultivated and used in suspension of all sales of plantain products at an interesting time when FDA has just pub­ the pharmaceutical industry fo r the glyco- until the identity of the ingredient can be con­ li shed proposed regulations for good manu­ f' sides di gox in and lanatos ides firmed." (ABC, 1997). Thi s was fo llowed fac turing practi ces (GMPs) which, if they had used in prescription heart by releases on June 12 by AHPA in which been instituted in the offending companies, medicati ons (e.g., Lanox in ). the trade associati on recommended "that all would have prevented the materi al fro m be­ The plant is annual, bienni al, current in ventori es of plantain leaf be tested ing resold . In fac t, at least one leading herb or perenni al and grows two immedi ately.... " AHPA provided the names di stributor, Frontier Herbs of Norway, Iowa, to three feet hi gh. Some and phone num bers of six analytical labora­ had received a shipment of the mislabeled so urces consider it more tories (AHPA, 1997). "plantain" and rejected the materi al after it tox ic than foxg love (D. pur­ Also on June 12, FDA released another fa il ed to pass th e tests applied in th e purea) (Morton, 1977). Al­ advisory giv ing more details of its investi­ company's in-house laboratory, according to though the venati on of Digi­ gation. FDA provided a list of distri butors Fro ntier Pres ident Rick Stewart (Stewart, Piantain, talis leaves (central ve in with and retailers whi ch had sold th e adulterated 1997). It is hi ghl y li kely that other compa­ Plantago maior branch ve ins coming off at pl antain, noting that the herb may have been nies with proper quality control measures

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CAsEMILL HoMESTEAD

ABC has a great vision for its new home, the historic 140-year-old Case Mill Homestead in Austin, Texas. Plans include 2 'lz acres of public-access medicinal plant gardens, a public-access library and reading room, a book store, conference and class rooms, laboratory space, and more.

The total cost of the new center will be $1.5 million. ABC has received funding commitments for $288,317.

You Can Jfefp I

HERBALGRAM readers can help realize this wonderful project. To send a pledge or contribution, please use the DONATE card on the reverse of this page.

The new home of the American Botanical Council. The beautiful and historic Case Mill Homestead For more information, in East Austin, a 140-year-old, three-story, see page 8 of this issue Colonial Revival house, surrounded by 2 1/z acres of HERBALGRAM, or contact of established herb gardens and well-maintained grounds. Wayne Silverman, Chief ~Arv1ERIC/'N &JT,ANJCAl Photo by Joni Weismann-McClain. Administrative Officer of COJf'JCIL ABC, at P.O. Box 201660, Austin, Texas, 78720-1660; phone 512/331-8868; fax 512/331-1924; email [email protected]. LEGAL AND REGULATORY

may have rejected similar material. The les­ REFERENCES Herb Research Foundati on. 1997a. Potential Heal!h Hazard : Pl antai n BelievedAdul!erated with Digitali s Lanata. June American Botanical Coun cil. 1997. FDA Consumer Ad visory son in the Chomper issue is that despite tre­ 13. Alert. June II . Herb Research Foundati on. 1997b. Mi croscopist referral for mendous progress being made by many American Herbal Products Association. 1997. Herb Adul!era­ members of the herb industry in areas of qual­ tion Advisory. June 12 . di gita li s testing. June 16. M orrisson. J. 1997. Perso nal communica ri on. Jul y 2. FDA. 1997a. FDA Wams Aga inst Consuming th e Arise & ity control, some importers, di stributors, and Shine Product ··chomper:· May 14. M ort on. J. 1977. Major Medicinal Plallts. Charl es C. manufacturers still need to increase their FDA. 1997b. FDA Wams Consumers Against Dietary Supple· Thomas. Stewart. R. 1997. Personal communi cati on. Jun 27 . level of GMP. 0 ment Products th at May Contain Digitali s Mislabled as ·'Plantai n: · June 12.

Commission on Dietary Supplements Labels Releases Draft Report to Public by Evelyn Leigh

On June 24, the Commission on Di­ regulation, and incorrectly stated that the "That's easier to recommend than actuall y etary Supplement Labels (CDSL) made pub­ CDSL recommended regulating some herbs implement," McCaleb conceded. "However, lic the draft report of its recommendations as over-the-counter (OTC) drugs. McCaleb it 's clear that the information gathered to President Clinton, Congress, and the Sec­ emphasizes that no recommendation was through th e current FDA surveill ance sys­ retary of the Department of Health and Hu­ made to remove herbs from the dietary tem is often not particularly useful, because man Services. The CDSL plans to release its supplement category. it is unqualified and typically not followed final report in August 1997. In reality, the Commission recom­ up." McCaleb beli eves that a new survei l­ The public has until August 8 to offer mended that FDA pl ace a hi gh priority on lance sys tem might be modeled on the one comments on the draft report. At thi s time, the establishment of a natural products OTC used by the U.S. Poison Control Centers, the CDSL is only seeking factual corrections, drug review procedure. This could allow whi ch takes into account the circumstances not comments on the scope or philosophy of approval of drug claims for herbs in addi­ surrounding adverse events as well as out­ the report. A congressional briefing was held tion to claims already allowed for those herbs come. on Friday, June 20, for the staff of interested used as supplements. Other recommendati ons include the members of Congress. The seven-member Under such a system, natural products creati on of FDA expert advisory committees, CDSL was appointed by President Clinton could be approved for sale in two or more such as the one the agency consulted on ephe­ in November 1995 in order to provide ex­ different categories simultaneously, in the dra, to provide future input on supplement pert recommendations on ways to make di­ same way vitamin psyllium seed is currently labeling and approval issues. The CDSL also etary supplement labels more accurate and available as a dietary supplement and as an favors the establi shment of a separate Bo­ informative. ingredient in OTC products. This is consis­ tani cal In gredient Review (BIR) board to Commission member Rob McCaleb, tent with testimony to the Commission by advise the herb industry. "It was clear to the president of Herb Research Foundation the American Botanical Council (A BC) and Commission that botanicals are enough of a (HRF), said he is generally pleased with the the American Herbal Products Association separate fie ld of study that specific experts draft report. "It provides a wealth of back­ (AHPA) and others where a mechanism to are needed," said McCaleb. The BIR origi­ ground information that may help Congress approve therapeutic claims for herbs was nall y was conceived by HRF and propo ed and the Administration gain a better under­ suggested. to FDA by AHPA. The concept is also sup­ standing of the major issues in supplement The Commission report reaffirms that ported by the National Nutritional Foods labeling," he remarked. On the other hand, manufacturers should continue to bear re­ Association ( NFA). McCaleb noted that CDSL members were sponsibility for the safety of their products All organizations and individuals who unable to come to a consensus on some of and the accuracy of their labeling with re­ testified before the Commission during the their recommendations. "I would have to say gard to content and claims. The current lack public informati on-gathering meetings last that not one member of the Commission of adequate post-marketing surveillance sys­ year wi ll automati call y receive a copy of the agrees with every point," he said. tems for supplement-related adverse reac­ report. Others can request a copy by calling The release of the CDSL draft was re­ tions constituted another important topic of 3011650-0382 or fax ing 30 I /650-0398. HRF ported in the Los Angeles Tim es and USA discussion. The CDSL recommended that the has posted the executi ve summary of the Today on June 25. Unfortunately, both sto­ industry and FDA work together to develop CDSL draft report on its worldwide website ries misrepresented many of the facts sur­ an improved adverse effects tracking system. at www.herbs.org 0 rounding past and current dietary supplement HERBALGRAM No. 40 • 29 H e r lb t&li M ((]) n ((]) g r i11 JP lb. s Initiated by Numerous Groups WHO, USP, ESCOP, ABC, and AHP all working toward similar goals

by Mark Blumenthal

The growth, sophistication, and maturation of the herb The worldwide spread in the use of herbal medicines has pro­ duced various attempts to develop herbal monographs to define iden­ market in the U.S. inevitably lead to the issue of how herb tity and quality criteria as well as therapeutic information. The Ger­ quality can be obtained and maintained. The proper man Commission E has been publishing therapeutic monographs since 1984. The European Scientific Cooperative for Phytotherapy identity and quality of herbal products are being pushed (ESCOP) has been developing therapeutic monographs since 1991 by several factors: consumers and healthcare profession­ and the World Health Organization (WHO) has initiated a project to als are become increasingly interested in the potential write monographs on widely used herbs around the world. In the United Kingdom herbal monographs have been published since 1983. health benefits of herbal dietary supplements; the media Domestically, the move toward developing monographs has continue to pay increasing attention to these products; picked up steam. The United States Pharmacopeia (USP) in March 1995 passed a resolution to consider the development of monographs and state and federal regulators attempt to come to terms for herbs being used in the U.S. as dietary supplements. Since that with the various issues surrounding the quality and time, USP has published several monographs on botanicals (see be­ low). Perhaps one of the most ambitious projects is the American appropriate uses of herbs. Herbal Pharmacopoeia (AHP), a new organization begun by herbal­ ist Roy Upton in California. AHP has completed several monographs, The manufacture of herb products, like all food products, is subject including the extensive monograph on St. John's Wort (Hypericum to good manufacturing practices (GMPs), a set of regulations that perforatum) in this issue of HerbalGram. determines the proper procedures for manufacture, quality control The development and maintenance of quality assurance for and quality assurance of foods, drugs, cosmetics, and now, dietary herbs as drugs is not a new phenomenon. As far back as the late supplements. Previously, all herbs and other dietary supplements 1400s, pharmacists and botanists in Italy, concerned about the po­ were subject to the GMPs required of manufacturers of conventional tential of misbranding and adulteration, produced what is consid­ foods. With the passage of the Dietary Supplement Health and Edu­ ered today to be the first modern pharmacopeia (often written in the cation Act of 1994 (OSHEA), new GMPs designed specifically for more archaic pharmacopoeia, meaning literally, "abundance of dietary supplements were mandated. On February 6, 1997, the Food drugs"). The first pharmacopeia in the English-speaking world, Phar­ and Drug Administration published proposed GMPs for dietary macopoeia Londoninsis, was published in 1618 in England. How­ supplements. (See related article on page 24.) ever, typical of all medical and scientific works of the times, it was One of the issues surrounding GMPs is assurance of botanical written entirely in Latin. identity and quality. Many questions have faced the herb industry in The word monograph means a learned treatise dealing with this area: How can a manufacturer be sure that the material being one subject, usually, in the scientific community, a plant or animal suppli ed by an importer or other supplier is the proper botanical? genus or particular species. In the botanical world there are essen­ How can one be certain that the herbal materi al is properly identi­ tially three kinds of monographs: standards, therapeutic, and com­ fied as to correct genus and species? What objecti ve criteria are bined. A standards monograph, the type usually found in a pharma­ available to ensure that botanical material is not adulterated with copeia, deals with information to determine the proper identity of a other cheaper ingredients or that the herb in question meets some plant genus or genus and species. This includes the taxonomy and minimum standard for quality? nomenclature of the plant (according to the Linnean system of bo-

30 • HERBALGRAM No. 40 Pharmacopoeia Londinensis, 1650 (photo of actual original publication) . Courtesy of the Lloyd Library and Museum, Cincinnati, OH.

tanical classification and no­ successive edition, published menclature, including all approximately every ten years. synonyms), botanical de­ The section or monograph scription of the whole plant dealing with each drug ingre­ and plant parts, microscopic dient was often enl arged to in­ descriptions of cellular clude additional qualifications structures of various plant and parameters reflecting new parts, and various chemical methods of analysis as the sci­ assays to determine identity ences of microscopy and chem­ and purity. USP standards istry continued to advance. monographs are examples of Eventually, with the advent of this type. more modern pharmaceutical A therapeutic mono- drugs in the 1920s and 1930s, graph usually provides a definition of the plant drug (i.e. plant part, botanical ingredients fell out of general use in conventi onal medi­ nomenclature, etc.), a listing of key chemical compounds, uses and cine and by the 1936 edition of the USP (11th editi on), most herbal indications, contraindications (i.e., what conditions may be present ingredients had been dropped. In fact, in the I 00-year period from to preclude use of the herb), side effects, dosage (including per unit 1870 to 1970, the number of botanical substances li sted in the US P and total daily intake), form of administration (i.e., the dosage in fell from 636 to 68 (Boyle, 1991 ). tea, tablet or capsule, liquid extract, etc.), duration of use, interac­ USP also contains monographs on vitamins to set standards tions with other medications, and so on. Both the Commission E for their purity. Based on a resolution passed at its an nual meeting in and the ESCOP monographs are therapeutic. The Drug Information March 1995, USP is now producting monographs on herbs and other Division of USP has also produced two in this area. botanical ingredients, not just for possible future inclusion in the Then, occasionally there are combined monographs, in which USP itself, but for its USP Drug Information Di vision, which pro­ both the standards information as well as therapeutics are included. duces monographs on numerous materials that are not included in The WHO monographs and the AHP monographs are of thi s type. the USP but are spread worldwide through an extensive informati on network to drug regulators and scientists in foreign countries. USP USP is currently accumulating a database of botanicals that are approved The United States Pharmacopeia was founded in 1820 by a group of in other national pharmacopeias to make this information avai lable II physicians. The USP was recognized in the U.S. Food and Drug to the USP General Committee of Revision or its advisory panels in Act of 1906 as the official compendium in this country. The stan­ the event that questions regarding botanicals arise during the 1995- dards in the USP are thus legally enforceable. The USP has been 2000 Revision Cycle (Grady, l995b). In July 7-9, 1996, US P held revised regularly since publication of the first edition, which con­ its first-ever open conference on "Botanicals for Medical and Di­ tained materials used in drug preparations at the time. Many were etary Uses: Standards and Information Issues" in Washington, D.C. botanical; many were of mineral or even sometimes of animal ori­ During the conference the delegates met on various issues concern­ gin (e.g., leeches). ing quality control standards, safety, criteria for determining As medicine and pharmacy developed, new materials were efficacy, and related subjects. added and some were eventually deleted from the USP with each

HERBALGRAM No. 40 • 31 Table 1: Herbal Monographs by Various Organizations

Organization Genera/Information Monograph Comments Type

American Herbal 4 monographs Standards, Includes Chinese Pharmacopoeia Therapeutic and Ayurvedic herbs

British Herbal 169 monographs Standards Re ferenced Pharmacopoeia, 1996 revision

British Herbal 84 monographs Therapeutic Referenced Compendium corresponding to 84 herbs listed in 1990 edition of BHP

ESCOP 50 herbal monographs Therapeutic Referenced

German ± 433 monographs (including Therapeutic No longer being evaluated, Commission E revisions) and produced by German (ABC translation) 324 herbs and combinations government; ± 200 approved herbs Not referenced

USP Monographs on 1 1 herbs Standards (8), Therapeutic monographs Therapeutic (3) for USPDI

World Health 28 monographs Standards, Additional 25 monographs Organization covering 31 plant spec ies Therapeutic being developed

The overwhelming result of this conference was to give USP Additionall y, the Drug Information Division of USP has pre­ Executi ve Vice-President Jerome Halperin a "green light" for USP pared two Information monographs (ginger and valerian) that are to proceed with the development of herbal monographs. USP has focused on the therapeutics aspects in which the safety and efficacy moved forward and produced monographs that create a USP stan­ of the botani cals are discussed, as can be determined from the exist­ dard for various popular herbs in U.S. commerce- six draft stan­ ing scientific literatu re. The di vision has recently distributed a dards monographs for discussion purposes in the Pharmacopeia! negati ve information monograph on comfrey for peer review. Forum, a bimonthly publicati on of USP (see Table 2). The producti on of Drug Informati on monographs by USP could give added credibility to herbs and phytomedicines as physicians, pharmacists, and other health professionals and Table 2: poli cy makers read about the health benefits of various Monographs on Herb Quality Standards Produced by USP leading herbs in monographs created by USP. The net effect Standards Monographs Publication in Pharmacopeia/ Forum could increase herb credibility and acceptance independent of any future policy of approval or disapproval of the herbs by Valerian/ Powdered Valerian Jan-Feb 1997 the FDA. Ginger / Powdered G inger Mar-Apr 1997 Garlic/Powdered Garlic Mar-Apr 1997 THE GERMAN COMMISSION E G inkgo biloba leaf Mar-Apr 1997 The most widely acknowledged system for the development Ginseng (Asian) / Powdered Ginseng May-Jun 1997 of therapeutic monographs is that of the German Commission Feverfew / Powdered Feverfew May-Jun 1997 E. Commission E is a di vision of the German Federal Health Pending monographs: Authority (equivalent to our FDA). Since 1978 when it was St. John 's Wort/ Powdered St. John 's Wort Jui-Aug 1997 first organi zed and until it was terminated by an amendment Saw Palmetto berries Jui-Aug 1997 to the Medicines Act in August 1994, the Commi ssion E re­ view published 330 monographs covering 324 herbs used in Information Monographs Publication in USPDI German folk medicine, approving over 200 herbs as safe and Ginger root Pend ing effective for over-the-counter drug use. The 330 monographs Valerian root Pending cover more than 80 percent of the herbal medicine products in Comfrey leaf and root Pending the German market (Keller, 1996). (Actuall y, the commis­ Garlic Pending sion published approximately 435 monographs, including re­ Source: Srinivasa n, 1997; John so n, 1997 . visions, correcti ons, and replacements.) Commission E monographs are geared toward thera­ peutic information on each herb, giving the taxonomic no-

32 • HERBALGRAM No. 40 The First Official Pharmacopoeia. The idea of a relati ons. The professional groups received official pharmacopoeia w ith official statu s, to be followed by advice and guidance from the powerful Dom inican all apothecaries, originated in Florence. The Nuovo monk, Savonarola (seated, foreground), who, at the Receptario, originally written in Italian, was publ ished time, was the political leader in Florence. and became the legal standard for the city-state in Pa inting by Robert Thorn for Great Moments in 1498. It was the result of collaboration of the Guild of Pharmacy by Parke, Davis and Company, 1966. Apothecaries with the Medical Society-one of the Courtesy of Warner Lambert. earliest manifestations of constru ctive interprofessional

mencl ature, botanical and chemical constituents, pharmacological Commission E, "thi s shows that herbal drugs are indeed a major properties, and pharmacokinetics and toxicology (in more recent problem for harmonization in the EU." (Kell er, 1996). monographs), as well as clinical informati on, including approved One of most interesting developments in the area of herbal uses, contraindicati o ns and side effects, special cauti ons, monographs is ESCOP, an affi li ation of national associations of phy­ pregnancy and lactati on informati on, interacti ons with other totherapy in Western Europe who coalesced in 1989 as a result drugs, dosage, overdosage informati on, special warnings, and so on, of the European harmonization process. ESCOP has produced a se­ if these are applicable. ri es of herbal monographs in order to respond to the increasing inte­ The American Botanical Council has translated these mono­ grati on of what was formerl y called the European Economi c Com­ graphs into English and, after numerous editori al delays, will pub­ munity (now European Uni on, or EU). The need fo r harmoni zed li sh them in book form this year. drug monographs for herbs was recogni zed so that there could be standards for botanicals popularly used in medicine and pharmacy ESCOP in Europe. The European market fo r herbs and phytomedi cines is character­ ESCOP has produced 50 new monographs as of June 1997, ized by the avail ability of a fairly large number of products. A re­ published in volumes ("fascicul es") of 10 monographs each. The port conducted in 1991 of the Member States (nati ons) indicated first two fascicul es were published in the fo rm of standardized dru g that a total of about 1,400 herbal drugs were avail able in the EEC. dossiers of European drug li censing, kn own as specific product char­ When thi s study focused on herbs used in at least half of the Mem­ acteri stics (SPCs) (Mills, 1997). Unlike a pharmacopeia! monograph ber States (5 out of a total of I 0 states), 145 herbal drugs were noted whi ch foc uses on standards fo r identity and quality, ESCOP mono­ (Keller, 1996). According to Dr. Konstantin Keller of the German graph s, like those of the German Commission E, deal with thera-

HERBALGRAM No. 40 • 33 Table 3: ESCOP Monographs

ESCOP monographs are published in Common Name Pharmacopeia/ Name Latin Binomial loose-leaf form, for insertion into a dedicated ring binder. They are Fascicule 1 available only in "fascicules" (vol­ Marshmallow root Altheae radix Althaea officinalis umes) of I 0 monographs each, as Birch leaf Betulae folium Betula spp. listed. ESCOP employs the tradi- Boldo leaf Boldo fo lium Peumus boldus tional pharmacopeia! name of the Calendula flower Calendula Flos Calendula officinalis herb as the title of each monograph. Fennel Seed Foeniculi Fructus Foeniculum vulgare The English common name and Latin St. John's Wort Hyperici Herba Hypericum perforatum binomials are added here for Linseed Lini Semen Linum usitatissimum convenience. Monographs are Java Tea Orthosiphonis Folium Orthosiphon spicatus available from ABC for $59.00 per Thyme herb Thymi Herba Thymus vulgaris fascicule, or $179.00 for all five Ginger root Zingiberis Rhizoma Zingiber officinale fascicules. ABC Order Desk, P. 0 . Box 20 1660, Fascicule 2 Austin, TX 78720-1660. Devil's Claw root Harpagophyti Radix Harpagophytum procumbens Phone 800/373-71 OS . Lemon balm leaf Melissa Folium Melissa officina/is Fax 512/331-1924. lspaghula (Psyllium seed) Plantaginis Ovatae Semen Plantago psyllium e-mail: [email protected] Ispaghula (Psyllium husk) Plantaginis Ovatae Testa Plantago psyllium Sage leaf Sal viae Folium Salvia officinalis Goldenrod herb Solidaginis virgaureae herba Solidago virgaurea Feverfew leaf and herb Tanaceti Parthenii Herba!Folium Tanacetum parthenium Dandelion leaf Taraxaci Folium Taraxacum officinale Dandelion root Taraxaci Radix Taraxacum officinale Nettle root Urticae Radix Urtica dioica

Fascicule 3 Garlic Allii sativi bulbus Allium sativum Anise seed Anisi fructus Pimpinella anisum Caraway seed Carvi fructus Carum carvi 1uniper berry Juniperi fructus Juniperus communis Iceland Moss Lichen islandicus Cetraria islandica Peppermint oil Menthae piperitae aetholeum Mentha x pipe rita Peppermint leaf Menthae piperitae folium Mentha x pipe rita Senega snake root Polygalae radix Poly gala senega Cowslip root Primulae radix ?rimula veris Rosemary leaf with flower Rosmarini folium cum flore Rosmarinus officinalis

Fascicule 4 Wormwood Absinthii herba Artemisia absinthium Arnica flower Arnicae flos Arnica montana Gentian root Gentianae radix Gentiana lutea Hops flower Lupuli flos Humulus lupulus Melilot Meliloti herba Melilotus officina/is Passionflower herb Passiflorae herba Passijlora spp. Blackcurrant leaf Ribis nigri folium Ribes nigrum Willow bark Salicis cortex Salix spp. Nettle leaf/herb Urticae foliurn/herba Urtica dioica Valerian root Valeriana radix Valeriana officina/is

Fascicule 5 Cape Aloes Aloe capensis Aloeferox Buckthorn bark (Frangula) Frangulae cortex Rhamnus frangula Witch hazel leaf Hamamelis folium Hamamelis virginiana Rest-harrow root Ononidis radix Ononis spinosa Psyllium seed Psylli semen Plantago psyllium Cascara sagrada bark Rhamni purshiani cortex Rhamnus purshianus Senna leaf Sennae folium Cassia senna Alexandrian Senna pods Sennae fructus acutifoliae Cassia senna Tinnevelly Senna pods Sennae fructus angustifoliae Cassia senna Uva-ursi leaf Uvae ursi folium Arctostaphylos uva-ursi

34 • HERBALGRAM No. 40 peutic aspects of each phytomedicine. Thus, ESCOP monographs include approved therapeutic uses and contain much of the format Table 4: WHO Monographs like recent Commission E monographs, including recommended dos­ age, side effects and contraindications (if any), and other specific Latin Name/ Monograph Title Common Name instruction, to help guide health professionals, industry, regulators, and patients (Blumenthal, 1991 ). Allium cepa Onion ESCOP monographs do not deal with quality issues; this is Allium sativum Garlic covered in other pharmacopeia! monographs. For example, the Eu­ Aloe vera gel Aloe vera ropean Pharmacopoeia includes 60 monographs on herbal drugs. Aloe vera juice Aloe vera An additional 45 draft monographs ha ve been published in the Astragalus membranaceus Astragalus Pharmeuropa for comments. According to Keller, "Thi s cooperative 8 rucea javanica Ja va brucea Bupleurum falcatum Bupleurum approach will greatl y facilitate harmonizati on of herbal remedies." Bupleurumfalcatum p Bupleurum (Keller, 1996). var. scorzonerifolium The 50 ESCOP monographs published to date are generally Centella asiatica Gotu kola more complete than those of Commission E and contain the added Chamomilla recutita Chamomile benefit of being referenced. Commission E monographs are not. Cinnamomum verum Cinnamon Unfortunately, the ESCOP monographs, despite providing an excel­ Cinnamomum cassia Cassia lent overview of each botanical, are not available here in the U.S.; Coptis chinensis Goldthread they must be ordered directly from ESCOP in the United Kingdom. Coptis deltoides Goldthread For more information, see the previous article on ESCOP in Herbal­ Cop tis japonica Goldthread Gram (Blumenthal, 1991 ). Monographs are available from ABC. Curcuma longa Turmeric See Table 3. Echinacea angustifolia Echinacea va r. angustifolia WHO MONOGRAPHS Echinacea angustifolia Echinacea In 1994 WHO began the compilation of a list of herbs that are widely va r. strigosa used in primary health care in various countries around the world in Echinacea pallida Ec hin acea Echinacea, purple coneflower order to consider developing monographs on each botanical (Zhang, Echinacea purpurea Ephedra sinica Ephedra, rna huang 1994). This move is consistent with WHO's previous publication of Ginkgo biloba Ginkgo its "Guidelines for the Assessment of Herbal Medicines," calling Panax ginseng Ginseng, Asian for the development of monographs to help define the quality of Glycyrrhiza glabra Licorice herbal medicines used as either "traditional medicines" and/or as Glycyrrhiza uralensis Li corice approved nonprescription (over-the-counter) drugs. (WHO, 199 1). Paeonia lactiflora Peony WHO engaged the assistance of Prof. Norman R. Farnsworth Plantago afra Psyllium of the Program for Collaborative Research in the Pharmaceutical Plantago indica Psy llium Sciences at the College of Pharmacy of the University of Illinois in Plantago ovata Psy llium Chicago to develop the WHO monographs. They were compi led Plantago asiatica Psy llium from the Napralert database by Professor Harry H. S. Fong, Gail Platycodon grandijlorum Platycodon Mahady, Ph.D., and Charlotte Gyllenhaal, Ph.D ., at the University Rauvolfia serpentina Indian snakeroot of Illinois in Chicago. A new li st of 30 plant species is being consid­ Rheum o.fficina/e Rhubarb ered for the second volume, as funding is made ava il able (Mahady, Rheum palma tum Rhubarb 1997). Currently, 25 monographs encompassing 28 plant species Cassia senna (leaf) Senna leaf on WHO's "Widel y Used Medicinal Plants" list are scheduled to be Cassia senna (fruit) Senna pod Thymus vulgaris Thyme published in book form as Volume I in 1997. The herbs represent Thymus zygis Thyme widely used herbs and medicinal plants from various geographi cal Valeriana o.fficinalis Valerian regions. Zingiber o.fficinale Ginger The li st of WHO monographs is shown in Table 4.

AMERICAN HERBAL PHARMACOPOEIA In 1977 Prof. Farnsworth proposed to the American Society of Phar­ macognosy (ASP) that it develop a Botanical Codex, a li sting of continued on page 37 monographs describing and offering analytical standards for the herbs and medicinal plants that were becoming increas ingly popular in folk medicine and commerce in the U.S. Unfortunately, ASP had neither the funding nor the foresight to initiate such a program. In 1988 when the American Botanical Council was established, one of its primary goals was to develop such a codex. However, due to funding limitations and other organizational and publication priori­ ties, ABC did not initiate such an extensive research and publishing project, choosing instead to make avail able monographs already existing by translating those of the German Commission E.

HERBALGRAM No. 40 • 35 II AMERICAN HERBAL PHARMACOPOEIA TM

The American Herbal Pharmacopoeia (A HP) was formed as a non-profit, tax-exempt [50l(c)(3)] organi zation in Santa Cruz, California. Its primary mission is to develop authoritative monographs on the quality and therapeutic aspects of botanical medicines. HerbalGram is pleased to be able to present the fir t publication of an AHP monograph. On the following 32 pages is the complete text of AHP's mono­ graph on St. John's Wort, Hypericum perforatum. For more info rmation, please see the article on herbal monographs on page 30 of thi s issue. Additional information on AHP is avail able by contacting AHP, Box 5159, Santa Cruz, CA 95063. ph : 408-461-6317; email: [email protected]; web page: herbal-ahp .org

AMERICAN HERBAL PHARMACOPOEIA SUPPORTERS

Benefactors (have generously provided contributions of $1 0,000 or more) Planetary Formulas

Patrons (have supported the work of the AHP with contributions of $5,000-$9, 999) Capsugel Enzymatic Therapy National Nutritional Foods Association

Sponsors (have actively participated in the AHP with contributions of $1 ,000-$4, 999) American Herbal Products Assoc . Meland Herbals Bio-Botanica, Inc. Natrol Chemco Nature's Apothecary Herbs Etc . Nature's Herbs Frontier Cooperative Herbs Nature's Life Futurebiotics Nature's Pathways GAIA Herbs Nature's Plus lndena New Hope Communications Ind iana Botanic Gardens, Inc Traditional Medicinals Jarrow Formulas , Inc . Wakunaga of Ameri ca Co., Ltd. Paul 0 . Koether David Winston

Contributors (have assisted the efforts of the AHP with contributions of up to $999) Blessed Herbs, Inc . Placerville Health Food Botanicals International Quantum, Inc. Ginco International Starwest Botanicals, Inc . Glenn Larkin San Francisco Herb Co. Herb Pharm Steve Schecter Herbs for Kids UniTea Herbs Kathy Larson Weider Nutrition Group Maitake Products, Inc . Yellow Emperor, Inc . MediHerb Kenneth Weiss Motherlove Herbal Company White Crane Trading Co. M ichael McGuffin Wild Wonderful Farms Now Natural Foods

Resource Contributors (have provided necessary books, articles, services, and equ ipment [1996])

Alpha Chemical and Biomedical Laboratories, Inc. Murdock Madaus Schwabe American Botanical Council Napralert Bazaar of India Nature's Way BioMedics Laboratory New Chapter CCS Associ ate New Moon Extracts CRC Press, Inc . North American Reishi Gourmet Mushrooms Sabinsa Corp. Hauser Nutraceuticals The Haworth Press, Inc . Herb Research Foundation Trout Lake Farm Industrial Laboratories Inc . 36 • HERBAL GRAM No. 40 AMERICAN HERBAL• PHARMACOPOEIATM AND THERAPEUTIC CoMPENDIUM

St. John's Wort Hypericum perforatum

Quality Control, Analytical and Therapeutic Monograph

701/.

St. John's Wort. Hypericum perforatum, from Woodville's Medical Botany, 3rd edition, 1832, originally published in 1790-1793. Courtesy of Hunt Institute for Botanical Documentation, Carnegie Mellon University, Pittsburgh, PA.

JULY 1997 Copyright © I 997, American Herbal Pharmacopoeia™ Medical Disclaimer All rights reserved. T he information contained in this monograph represents a synthesis of the No part of this monograph may be reproduced, stored in a retrieval system or authoritative scientific and traditional data. All efforts have been made to assure the transmitted in any fo rm or by any means without written permission of the accuracy of the information and fi ndings presented. However, those seeking to American Herbal Pharmacopoeia. TM utilize botanicals as part of a health care program should do so only under rhe guidance of a qualified healrhcare professional. Statement of non-endorsement The reporting of rhe use of proprietary products represents studies conducted with these products and is nor meant ro be an endorsement of these preparations. Editor Authors Roy Upton, Herbalist History & Constituents Analytical Methods Additional Contributors American Herbal Roy U pton, Herbalist D awn M. Gatherum, Ph.D. Mary Cole Marquis, R .Ph. Pharmacopoeia American H erbal Pharmacopoeia Edward B. Walker, Ph.D. Medical Arts West Santa C ruz, CA Weber Stare University C harlottesville, VA Santa Cruz, CA O gden, UT Botany R. Lynn Shumake, R.Ph. Final Expert Reviewer Alison Graff, M .S. Veronica Burrerweck, Ph.D. U niversity of Maryland American Herbal Pharmacopoeia U rsula Lieflander-Wulf G lenwood, M D Robert Anton, Ph.D. Santa C ruz, CA AdolfNahrsredr, Ph.D . Jill Stansbury, N .D. Faculty of Pharmacy Alexander Wall, Ph .D. Microscopy N ational C ollege of Hilke W interhoff, Ph.D. Pharmacognosy Elizabeth Williamson, Ph.D . N aturopathic Medicine Wesrfalische Wilhelms Department Department of Pharmacognosy Battleground, WA Universirat University of Strasbourg The School of Pharmacy Miinster, Germany Research Administrator Strasbourg, France University of London Cathirose Petrone London, England Pharmacology Am erican H erbal Pharmacopoeia Jerry Con , Ph.D. Santa C ruz, CA Commercial Sources and Handling Pharmacologic Treatment D avid Bunting, Herbalist Research Program Rainbow Light N urritio nal Systems N ational Institute of M ental Santa C ruz, CA H ealth (N IMH) National Institutes of Health Rockville, MD Reviewers

Ambrose Amarquaye Amanda McQuade Crawford, David Hoffmann, MNIMH James Murch, R.Ph. Herb Pharm M N IM H Califo rnia Institute of Integral Studies Integrated Healing Arts Williams, OR O jai Center for Phyrorherapy San Francisco, CA Los Altos, CA Ojai, CA Marilyn Barrett, Ph.D. Josef Htilzl, Ph.D. Adolf Nahrsredr, Ph.D. Pharmacognosy Consulting Services Steven Denrali , Ph.D. lnsri ru r fur Pharmazeurische Editor, Planra Medica Redwood City, CA Denrali Associates Biologie, Der Phill ips-Universirar Westfal ische W ilhelms Troutdale, WA Marburg/Lahn Universirar Miinsrer Mark Blumenthal Marburg, Germany Miinsrer, Germany American Botanical Council Fred Evans, Austin, TX D.Sc., B. Pharm., Ph.D. Mark Lange, Ph. D. Andrew Pengelly, Herbalist Department of Pharmacognosy Industrial Laboratories National Herbalists Mary Bove, N .D., MNIMH University of London Denver, CO Association of Australia Brattleboro Natural Clinic School of Pharmacy New South Wales, Australia Brattleboro, VT London, England Glenn Larkin, M.S. Alpha Chemical and Xi Ping Wang, Ph.D. Francis Brinker, N.D. Trish Flaster, M.S. Biomedical Labs, Inc. GAIA Herbs Southwest College of Botanical Liaisons Petal uma, CA Harvard, MA Naturopathic Medicine Boulder, CO Tucson, AZ James Mattioda, R.Ph. Andrew Wei!, M.D. Steven Foster, Specialist in Arcana Pharmacy University of Arizona Richo Cech Medicinal & Aromatic Plants La Jolla, CA Scorrsdale, AZ Herb Pharm Fayetteville, AK Williams, OR Michael McGuffi n Hil ke Winterhoff, Ph.D. Jorg Grunwald, Ph.D. McZand Herbal, Inc. lnsrirur fiir Pharmakologie Phytopharm Consul ting Santa Monica, CA und Toxikologie Berlin, Germany Universirii r Miinsrer Dennis McKenna, Ph.D. Miinsrer, Germany AMERICAN Silena Heron, N .D. Marine on Sr. Croix, MN H ERBAL American Association of Q un Yi Zheng, Ph.D.

P HARMACOPOEIATM Naturopathic Physicians Slobodan Milosavljevic Madis Botanicals Sedona,AZ Faculty of Chemistry South Hackensack, NJ University of Belgrade ST. JoHN's WoRT Christopher Hobbs, L.Ac., Herbalist Belgrade, former Yugoslavi a M ONOGRAPH Institute fo r Natural Product Research Bonny Doon, CA 2 St. John's Wort, Hypericum perforatum. Photo ©1995 Steven Foster NOMENCLATURE

Botanical Nomenclature Hypericum perforatum L.

Family Clusiaceae (syn. Hypericaceae and Guttiferae)

Definition St. John's Wort consists of the whole fresh or dried plant or its components, containing not less than 0.04% naphthodianthrones of the hypericin group calculated as hypericin.

Common Names English: St. John's Wort, Klamath Weed (Bailey, 1949; Hickman, 1993) Chinese: Qian Ceng Lou (The Jianshu Institute of Botany et al., 1988) Dutch: St. Jan's Kraut (Pratt, 1853), Sankt Hans Urt (Madaus, 1976) French: Herba de Millepertuis (Bisset and Wicht!, 1994), Herba de Saint Jean, Toutsaine (Pratt, 1853) German: Johanniskraut, Johannisblur, Blutkraut, Herrgottsblut (Blumenthal et al., 1997; Bisset and Wicht!, 1994) Italian: Perforata, I peri co (Pickering, 1879), Pelatro (Benigni et al., 1971 ) AMERICAN Russian: Zwieroboij (Madaus, 1976) H ERBAL Spanish: Hipericon (Farmacopea Mexicana, 1925), Corazoncillo (Pratt, 1853) PHARMACOPOEIA™ Swedish: Johannesort (Madaus, 1976) ST. JoHN's WoRT M oNOGRAPH

3 HISTORY The name Hypericum is a derivation of two Greek words, hyper and eikon which translate "over" and "icon" as in "over an apparition," alluding to its use in ancient times for protecting against demonic possession and its reported ability to protect one from "evil spirits." An earlier derivation of the name yperikon was first used by the Greek physician Euryphon (Hobbs, 1990). Because of these uses, one of its common names throughout antiquity was Fuga Demonum, the Devil 's Scourge (Fernie, 1897; Pratt, 1853). The species name perforatum is based on the perforated appearance of the leaves due to their translu­ cent leaf glands which can be observed when held up to light. There are numerous explanations as to how the name St. John's Wort was derived. One refers to the fact that the flowers bloom around St. John's Day (June 24), another is that the red pigments which are exuded when the buds and flowers are squeezed were associated with the blood of St. John the Baptist, and yet another refers to an ancient English tradition of throwing the flowers into a bonfire on the eve of St. John's Day. The first association made in the United Kingdom between Hypericum and St. John is reflected in a Gaelic legend dating from the 6th century in which it is said that the missionary St. Columba always carried a piece of St. John's wort because of his high regard for St. John (Hobbs, 1990).

The primary ancient medical herbalists, including Hippocrates, Pliny, Dioscorides, Theophrastus, and Galen wrote about the medicinal properties of St. John's wort, noting its use as a vulnerary (wound-healing), diuretic, and treatment for neuralgic conditions such as sciatica and hip pain. Mattioli wrote of its use as an emmenagogue, diuretic and antimalarial (Bombardelli and Morazzoni, 1995). Gerard wrote that its use as a balm for wounds, burns, ulcers, and bites was without equal (Gerard, 1633). The oil made from the flowers was listed in the first Pharmacopoeia London ensis (1618). It has persisted throughout the centuries as one of the most reliable vulnerary oils.

Hypericum was brought to the Northeastern United States by European colonists (Pickering, 1879). In the late 1700 s, Jean-Bernard Boss u reported on the local Louisiana use of Hypericum oil for healing wounds (Vogel, 1970), a use subsequently popularized by modern homeopathic practitioners. The most common uses of Hypericum have been for the treatment of depression and various psychological and neuralgic disorders, as an anthelmintic for worms, a vulnerary for minor hemorrhages, a tea for bedwetting in children, and as a diuretic (Fernie, 1897; Linde eta!., 1996; Rao et al., 1991 ; Vickery, 1981). The use of Hypericum for each of these purposes persisted among the modern medical herbalists of America. Some of the key figures among the Eclectics, most notably John King and Finley Ellingwood, valued Hypericum for its astringent, sedative and diuretic properties (Ellingwood, 1919; King, 1866). King also used it for depression, an effect that has since been firmly established (Linde et al., 1996). Hypericum has been listed in the pharmacopoeias of many countries, including Czechoslovakia, France, Germany, Poland, Romania, and Russia (Hobbs, 1989; Reynolds, 1993). St. John's Wort Hvpericum perforatum. DESCRIPTION Photo© 1997 Martin Wall Botanical Description Erect, many-stemmed, herbaceous perennial, 1.0-10.0 dm from a taproot. Leaves: 1.5-4.0 em long, sessile, opposite, glabrous, with pellucid glands, elliptical to linear-oblong. Inflorescence: Large, rounded or flat-topped, compound cymes with 25-100 flowers each. Flowers: Perfect, radi ate; sepals 5, free, 4.0-6.0 mm long, linear-lanceolate, acute or acuminate, sometimes with black dots; petals 5, free, 8.0-12.0 mm long, yellow with black dots along margins only; stamens 15-100 in 3-5 clusters; ovary superior, 3 carpellare, styles 3. Fruit: Septicidal capsule, 7.0-8.0 mm long, brown, strongly pitted seeds (Bai ley, 1949; Gleason and Cronquist, 1963; Hickman, 1993; Hitchcock and Cronquist, 1973; Mabberley, 1987; Turin et al. , 1968). Distribution: There are approximately 370 species in the genus Hypericum (Mabberley, 1987). H perforatum is native to all of Europe and As ia except for the Arctic regions.

AMERICAN It has been introduced to the United States where it has naturalized. Ranchers consider it

HERBAL to be a noxious weed in pastures. Efforts to eradicate it have led to the introduction of the

P HARMACOPOEIATM flea beetle, Chrysolina quadrigemina (Hickman, 1993; Turin et al., 1968).

ST. JoH N's WoRT M ONOGRAPH 4 Macroscopic Description Physical Characteristics: T he dried herb consists mainly of the fl owering tops, including the leaves, unopened buds and flowe rs. The leaves are elliptic to oblong, small and oppositely set, without stalks, mainly green to pale green and glabro us with an entire margin. The flower petals are yellow to yellowish-brown and may still be present in the dried material either whole or fragmented in the cymes. Both petals and leaves are characterized by numerous, punctate glands approximately 0.5- l mm in di ameter. These can be read ily observed with a lOX hand lens. The leaf glands appear transluce nt when held against light. Those on the petals appear as black dots along the margins. T he stems are pale green, cylindrical, and holl ow with faint, longitudinal, opposing ribs that distin­ guish H. perforatum from other species. Powder: Greenish to yell owish-brown with the yellow becoming more pro nounced as the perce ntage of fl owers and unopened buds increases. Odor: Distinct, sli ghtly sweet and aromatic, so mewhat balsa mic. Taste: Slighdy sweet, mildly birrer, somewhat res inous and as tringent (Bisset and Wicht! , 1994; Bradl ey, 1983; H obbs, 1989). St. John's Wort. Hypericum perforatum showing characteristic punctate glands. Photo © 1997 Jill Stansbury

Table 1: Macroscopic characteristics of various Hypericum species

Plant Stem Lea ves Flowers

H. perforatum two-winged, egg-shaped to elongated, sepa ls: lanceolate, acute, twice as glabrous obtuse, very short long as the ovary; petals: oblique petiolate, translucent. and egg-shaped, one-side serrated, ma rked with black dots marked with black dots and lines

H. barbatum round, glabrous elon gated-lanceolate, lower side sepals and bracts: bristly gray-green glabrous, scattered fringed; petals: ova l black dots, somewhat translucent or not at all

H. hirsutum round , hirsute elongated (2 x 5 em ). obtuse, sepals: lanceolate, cil iated with hirsute, black translucent dots, petiolate black glands (tentacle-like) ; free from dark glands petals: symmetric, twice as long as sepal, occasional black glands

H. maculatum fou r-edged, gla brous, sessile, el liptic or egg­ sepals: broad elliptic, obtuse; somew hat red shaped, obtuse, black petals: symmetric towards the bottom translucent dots

H. montanum round, glabrous large (8 x 3 em). some obtuse, sepals : like H. hirsutum, some acute, glabrous, the edge bracts: ciliated; petals: oval covered with dark glands, young leaves dotted, faintly translucent

H. tetrapterum four-winged, glabrous broad egg-shaped, obtuse, sepals : lanceolate, acute, gla brous, half-clasping the smooth margins; petals: stem, densely punctuated with elongated, obtuse, smooth small dots, rare black glands margins (Berghofer and Holzl, 1986)

AM ER ICAN H ERBAL P HARMACO POEIA'"

ST. JoH N's WoRT M ONOGRAPH

5 Microscopic Description Powder: Greenish to yellowish-brown. Leaf and Flower: Leaf fragments abundant; most containing large, characteristic, hyperi­ cin oil glands, some with red contents, especially near the margin. Upper epidermis consists of polygonal cells with slightly sinuous, beaded anticlinal walls; and underlying small palisade mesophyll visible. Lower epidermal cells sinuous except over a vein, where they are straight-walled and beaded. Cuticle fairly thick, smooth, vis ible in transverse section and at the margin. Stomata paracytic or occasionally anomocytic, on lower epidermis only. Flower parts consist of calyx fragments, similar to those of leaf with numerous hypericin glands; corolla with straight-walled epidermis on the outer surface, sinuous walls on the inner surface, oil glands visible beneath, often elongated with reddish or yellowish contents. Anther and filament fragments typical but not diagnostic. Pollen grains spherical or elliptical with three pores and a smooth or faintly warted exine. Stem pieces numerous; epidermis of elongated cells with straight, beaded anticlinal walls, stomata paracytic with two small, parallel adjacent cells. Tracheidal vessels, thick-walled tapering fibers and lignified parenchyma common in older stems, collenchyma from cortex and oil glands visible in younger stems. Trichomes absent.

Figure 1

Legend to figure 1. Upper epidermis of leaf near the margin, show ing beaded cell walls, underlying hypericin gland and cuticle visible near the margin.

2. Leaf upper epidermis w ith underlying palisade mesophyll.

3. Low er epidermis of leaf with paracytic and anomocytic stomata; epidermal ce ll s over the vein are elongated, straight-walled, and beaded .

4. Outer surface of corolla of flower w ith underlying oil gland.

5. Fragment of corolla with elongated oil gland in side vi ew.

6. Inner epidermis of corolla.

7. Pollen grains.

8. Epidermis of stem with characteristic beaded w alls and paracytic stomata.

AMERICAN H ERBAL

PHARMACOPOEIA TM

ST. JoHN's W oRT M ONOGRAPH

6 COMMERCIAL SOURCES AND HANDLING Varying qualities of both dried and fresh Hypericum are available in the commercial market and differ according to the percentage of leaf to flowering material, time of harvest, care of handling, and drying conditions.

Collection Most domestic material is harvested from naturalized plants in the Pacific Northwest and Eastern states. Collection generally takes place from June through September, but will vary with elevation and local climate. The following information is useful for determining optimum harvesting times.

Concentrations of Hypericum 's two primary classes of constituents, the naphthodianthrones (hypericin and pseudohypericin) and various flavonoids, vary greatly due to numerous factors, including varietal and species differences, harvesting and handling practices, moisture, altitude, and the different plant parts. The flowering tops should be gathered immediately before to immediately after opening and typically contain a mixture of buds and blossoms. The flowering tops contain the highest concentrations of napthodianthrones and flavonoids, followed by the uppermost leaves and flowers during the budding and blooming period (Benigni eta!., 197 1; Southwell and Campbell, 1991 ).

Flavonoid and procyanidin concentrations are reported to be highest in the flowers during the budding stage immediately before flowering (11.71 %), followed by the leaves and stems (7.4%) (Tsitsina, 1969). Flavonoid concentrations are also reported to be highest in plants growing in higher altitudes and those growing on northern slopes where the weight of the plant is lower than that of plants growing in southern exposure (Brantner eta!., 1994; Tsitsina, 1969; Zhebeleva, 1973).

The highest concentration of I3, 118-biapigenin occurs in buds and flowers , while the fruit was reported to contain very low concen­ trations. No trace was reported in the stems and leaves (Berghofer and Holzl, 1987). Hyperin is highest in the flowers (3%), followed by the leaves (1. 05-1.80%). Only traces are found in the stems (0. 13%) (Maksyutina and Koger, 1971). Quercetin is found in the leaves and flowers (0.1-0.582%) with trace amounts in green leaves, higher amounts in red-colored leaves, even higher amounts in the leaves during flowering, and the highest amounts in the flowering tops (Smith eta!., 1996). Rutin is found in all plant pares, but is much higher in the leaves (2%) during the budding stage than in the flowers (0.095%), is higher in plants growing in dry conditions versus those growing in moist conditions, and is reported to be highest when the plant is harvested in the evening. In leaves, hyperin and rutin domi­ nate, while in the flowers hyperin and quercetin are the dominant flavonoids. Well-balanced water conditions are reported to increase the content of total flavonoids, while stressful water conditions are reported to have the opposite effect (Aiyukina, 197 1) . Browned leaves possess low levels of flavonoids (Dobrowolska eta!., 1970; Prokoshava and Shatunova, 1985; Razinskaite, 197 1).

Narrow-leafed varieties, which have a relatively high number of oil glands (6 .2 per mm), are reported to yield significantly higher concentrations of Hypericum perforatum, cut and hypericin than broad-leafed varieties (2.2 oil glands per mm) (Southwell and Campbell, dried. Photo ©1 997 Roy Upton 1991 ). Hypericin and pseudohypericin diminish rapidly immediately after the flowers have bloomed and after pollination has taken place (Benigni eta!., 971; Brantner eta!., 1994).

The phenolic concentration, which gradually increases throughout the herb's AMERICM growing cycle, is highest at blossoming time and has been reported to be equivalent in the H ERBAL

leaves and flowers (Brantner et al., 1994; Razinskaite, 1970). It is similarly higher when PHARMACOPOEIAn< Hypericum is growing at temperatures above 14' C (57' F) and is higher when growing in dry versus wet conditions (Maisenbacher and Kovar, 1992a). ST. JoHN's Wo RT M ONOGRAPH

7 Essential oil content in the stem is very small and is greater in the mature seed capsule. T he esse ntial oil content of the entire plant is also richer before fl owering (0.26%) than when in fl ower (0.11 %). When the stem is eliminated the plant yi elds up to 0.3 5% esse ntial oil (Beni gn eta/., 1971; ESCOP, 1996).

T he phloroglucinols, consisting mos tly of hyperfo rin and adhyperforin, occur exclusively in the fl owers and capsules. T heir levels increase considerably during rh e fo rmati on of the capsul es with hyperforin increasing from 2. 0% in the fl owers to 4.5% in the capsules, based on dry weight, and polar hyperforin­ li ke compounds increasing fro m 0. 05-0.3%. A ten-fold increase of adhyperfo rin fro m 0. 2% in the fl owers ro 1.9% in the capsules has been reported (Benigni et a/., 1971; Bro ndz eta/., 1982; Bys trov, 1975; Maise nbacher and Kovar, 1992a).

T he fl owers are repon ed ro yield carorenoids (Cosres and Thomas, 1967) and are also reponed ro conrain rh e highest concentrati on of xanrhones (H ansel eta/., 1993).

Based on a review of the literature, it appears that properly dried herb, including flowers, buds, and the middle ro the ro p leaves and secondary stems yields the highest concentra tion and broades t range of naphthodianrhro nes and fl avo noids (Berghi:ifer and H i:i lzl, 1987; Southwell and Campbell , 1991; Tsits ina, 1969). Care should be taken ro harvest only the middle ro the top porti on of the plant, approximately the ro p 30-60 em (12-24 in). H arves ting the lower leaves will result in a significant lowering of constituent concentration Hypericum perforatum, powder. (ESCOP, 1996). Photo ©1997 Roy Upton Caution: Care should be taken when collecting Hypericum. Accounrs of contact phorosensirivity due ro co ll ecting have bee n repon ed, including rhe occurrence of second degree blisters on eyelids and forehead. W hen collecting, keep hands covered and avoid contact wirh eyes and unpro tected skin (Upro n, 1997). Notice: H erbicides have been widely used on both domestic and European Hypericum.

Fresh Processing Fresh planr material should be processed as soo n after harves ting as possible. If shipmenr is requi red, the materi al should be d ry packed wirh a refrigeranr or shipped under refrigera­ tion and prorecred fro m light to preve nr oxidation. To avoid damaging rhe material, rhe refrigeranr should not co me in direct contact wirh rh e plant.

Drying Va ri ous di rections for drying Hypericum are provided in the literature. Five different methods were examined, wirh identical samples harves ted in rhe bl ooming srage to determi ne rhe optimum drying conditions for co nsriruent preservati on. Each method was repeated fi ve ri mes under rh e same conditions. T he highest concentratio ns of hypericin and pseudohypericin were observed afrer mi crowave drying (Branrner et al., 1994). ) Treatment wirh li quid nitrogen (N2 and subsequent freeze drying showed significantly higher concentrations of fl avo noids and procya ni dins.

T he mos r suitable procedure fo r preservation of all constiruents proved ro be drying ar 70° C (158° F) for 10 hours. H ansel et al. , (1993) provide di ffe rent instructions; they say rhar rhe herb is usually cur ar rhe beginning of irs fl owering season Qune-Augusr) and dried in bundles. For maximum preservatio n of rhe oils, rhey assert thar drying musr happen quickly bur ge ndy, and should be done on drying fl ars during wa rm weather or wirh rhe help of moderate artific ial hear ar 30-40° C (86-104° F) during humid cool wea th er. Orhers repo rt rhat drying Hypericum in sunlight can result in as much as 80% hyperi cin loss due ro oxidati on and recommend that Hypericum be air-dried in rhe shade

AMERI CAN (Araya and Fo rd, 1981). H ERBAL PHARMACOPOEIA'"

ST . Jo HN's W o RT M ONOGRAPH

8 Storage Protecting Hypericum from light is the most important factor for preserving the photosensitive naphthodianrhrones and phloroglucinols. Hypericin content has been shown to drop significantly in powdered extract, tablet and juice preparations when stored at temperatures of 60" C (140° F) for more than six weeks. Dry extracts stored at 20" C (68° F) were found to remain stable for at least one year (Adamski and Sryp- ~ekowska , 1971; Benigni eta!., 1971).

The hyperforins are lipophilic and unstable when exposed to hear and li ght (Nahrsredr and Butterweck, 1997, in press) and can degrade in as little as 14 days. Stabili ty (in absence of air) was increased to six months in a preparation extracted in ethanol (Maisenbacher and Kovar, 1992b).

Adulterants Hypericum perforatum may be adulterated with other Hypericum species and can be differentiated from them by strict adherence to the stem characteristics as described (see macroscopic description). Material which has been demonstrably oxidized should nor be used. While H maculatum has a constituent profile that is similar to H perforatum and may also be found in trade, it consistently has been found to possess lower concentrations of naphrbodianthrones, total flavonoids, and procyanidins than H perforatum. H maculatum also does nor contain rutin (Brantner et al., 1994).

Preparations Infusions: Tea should be freshly prepared from 2 tsp. of herb per 150mL (~ 5 oz.) of boiling water. Steep 10 minutes and strain (Hansel et al., 1993). Tea made in 60-80° C (140-176° F) water has been reported to yield approximately 6-1 Oo/o of the avail able hypericin and 35% of the ava ilable pseudohypericin (Debska and Zmudzinska, 1982; Niese! and Schilcher, 1990).

Tinctures: Hansel et al., (1993) give directions for preparing a simple tincture by using 20 g chopped drug (dried shoots cut one hand-width below the bloom) with approximately I 00 mL ethanol (70%) extracted, filtered , and preserved in dark bottles. Hypericin yields are reported to be highest when extracted in 70-80% alcohol and heated to 70-80° C (158-176° F) (Dyukova, 1985; Georgiev et al., 1985; Wagner and Bladr, 1994), with one reference suggesting that the herb be decocted in the menstruum for 30 minutes (Kowalewski et al., 1981). When the particle size is less than 0.25 mm, extraction of tannins occurs sooner than with larger particle sizes, although the actual yield is reportedly independent of particle size (Lis t and Schmidt, 1989).

Oil macerates: Various guidelines are available for preparing oil preparations. Typically only flowers are used in such preparations. Some recommend that the flower be digested (macerated) in oil at 4Y C (113° F) for 10 days (Smith et al., 1996), while others recommend 70o C (158o F) for 12-24 hours (Hobbs, 1989). Exposing the preparation to sunlight during the extraction process has been reported to result in a four-fold increase in flavonoid content calculated as quercetin (Maisenbacher and Kovar, 1992b) and also to yield higher amounts of rutin than preparations macerated in the dark (Smith et al., 1996). Additionally, two-fold increases of hypericin have been reported in oil preparations in which the marc has been further extracted with alcohol and mixed with the oil (Georgiev eta!., 1983).

Standardized extracts: Numerous standardized extracts are ava il able yielding from 0.4 to 2.7 mg of hypericin per daily dose. These are prepared in a variety of ways accord­ ing to the various manufacturers.

CONSTITUENTS Hypericum contains numerous compounds with documented biological activity. Most AM ER ICAN researchers consider irs effects to be due to a variety of constituents rather than any single H ERBAL component. Constituents that have stimulated the most interest include the P HARMACOPOEIA"' naphthodianthrones hypericin and pseudohypericin, a broad range of flavonoids, includ­ ing quercetin, quercirrin, amentoflavone and hyperin, the phloroglucinols hyperforin and ST. JoHN's W oRT adhyperforin, rhe essential oil; and xanthones. M ONOGRAPH

9 Naphthodianthrones (< 0.1-0.15%*) The naphthodianthrones (Tables 2 and 3) include hypericin, pseudohypericin, isohypericin, and emodin-anthrone. It has been reported that dried flowers can yield as much as 1.8o/o hypericin. Ir has also been reported that pseudohypericin concentrations are two to three times greater than hypericin. In fresh material protohypericin and protopseudohypericin are also present. These biosynthetic precursors are transformed into hypericin and pseudohypericin by exposure to light. Cyclopseudohypericin is also cited and is an oxidation product of pseudohypericin (DAC, 1986; ESCOP, 1996). *Average yield of cur and dried plant materials, including stem, leaf, and flowers.

Table 2: Hypericin content in various Table 3: Hypericin content in various parts of H. perforatum parts of H. perforatum

Sample Content in Weight % Sample Content in Parts Per Million

Young plant (12 em tall) 0.027 (Benigni eta/., 1971) Flowers and buds 2150 ppm Whole plant w/ flowers 0.036-0.2 (Benigni eta/., 1971) Capsules 730 ppm Whole plant w/ buds 0.042 (Benigni eta/., 1971) Top leaves 380 ppm Dried flowers 0.196-1 .8 (Benigni eta/., 1971) Bottom leaves 290 ppm Fresh flowers 0.09-0.12 (Hansel eta/, 1993) Side stem 120 ppm Petals 0.245 (Benigni eta/, 1971) Main stem 40 ppm Leaves (average) 0.019 (Benigni eta/., 1971) Narrow-leafed varieties 1 040-1630 ppm 2 Stem 0.021 (Benign eta/., 1971) (6.2 oi l glands/mm ) Broad-leafed varieties 370-580 ppm (2.2 oil glands/mm2)

(Hi:ilzl and Ostrowski, 1987; Southwell and Campbell, 1991 )

Flavonoids (flowers 11.71%, leaves and stalks 7.4%) The proanthocyanidins, consisting of dimers, trimers, tetramers, and high polymers of catechin and epicatechin, represent approximately 12o/o of the dried weight of the aerial portion of the plant (Akhtardzhiev and Kitanov, 197 4; Bombardelli and Morazzoni, 1995).

T he following flavonols have been identified: kaempferol, lureolin, myricetin, quercetin (2o/o); flavonol glycosides: quercitrin (0 .3-0.524%), isoquercitrin (0.3o/o) (Dorossiev, 1985; Koger, 1972), hyperin/hyperoside (0.7-l.lo/o) (Hansel eta!., 1993), 13, Il8-biapigenin (0.1-0.5%) (Berghofer and Holzl, 1987; Hansel et al., 1993), amentoflavone/13', Il8-biapigenin (0. 01-0.05% in flowers) , 13, Il8-biapigenin (0.1-0.5%) and rutin (0.3o/o) (Akhtardzhiev et al., 1984; Berghofer and Holzl, 1989; Kitanov, 1987).

Caffeic (0.1 o/o), chlorogenic, p-coumaric, ferulic, isoferulic and gentisic acids along with leucocyanidin have also been described (Benigni et al., 1971; Seabra et al., 1992; Stoyanova et al., 1987) (Table 4).

Essential Oil (0.059-0.35%) The essential oil consists mostly of monoterpenes (pinenes) and sesquiterpenes (Benigni et al., 197 1). Of these, the primary compounds include the saturated hydrocarbons 2-methyl-octane (16.4%) and a-pinene (1 0.6o/o); also present are traces of 2- methyl-decane, 2-methyl-butenol and undecane, B-pinene, a-terpineol, geraniol, traces of myrcene, limonene, caryophyllene, humulene, CI Ga nd c 24 n-alkanes, and c24 ,C26 and c28 AMERICAN n-alkanols (Brondz and Greibrokk, 1983; Brondz et al., 1983; Mathis and Ourisson, 1964; H ERBAL Nahrstedt and Butterweck, 1997, in press) (Table 5). PHARMACOPOEIATM

ST. JoH N's WoRT MONOGRAPH

10 Table 4: Flavonoid content in various parts of H. perforatum

Constituent Plant Part Concentration in Weight %

Total flavonoids Flowers -11 (Tsitsina, 1969)

Total flavonoids Stems and leaves -7 (Tsitsina, 1969)

Quercetin Fl owers -0.1 (Benigni eta/., 1971)

Ouercitrin Whole herb/flowers 0.3-0.5 (Koget, 1972; Hansel eta!., 1993)

lsoquercitrin -0.3 (Hansel eta!., 1993)

Hyperin (hyperoside) -1 (Hansel eta!., 1993)

13, 118-biapigenin Fresh flowers 0.1-0.5 (Hansel eta/., 1993)

13, 118-biapigenin Stems and leaves Non-detectable (Berghbfer and Hblzl, 1989)

Amentoflavone (13 ', 11 8-biapigenin) Flowers 0 01-0 05 (Berghbfer and Hblzl , 1989; Hansel eta/., 1993)

Rutin Flow ers -0.1 (Benigni eta/., 1971 )

Rutin Leaves - 2 (Benigni eta/., 1971 )

Table 5: Content of essential oil in Hypericum perforatum

Sample Content in Weight %

Whole plant > 0.07-0.33 (Benigni eta/., 1971) Fl owering plant 0.059-0.11 (Benigni eta!., 1971) Plant before flowering 0.26 (Benigni eta/., 1971 ) Plant w ithout stem Up to 0.35 (Benigni eta/., 1971) Fresh flowers 0.25 (Hansel eta!., 1993)

Phloroglucinols This class of compounds consists predominantly of the prenylated derivatives of the phloroglucinols hyperforin (2.0-4.5%) and adhyperforin (0.2-1.9%) (Brondz eta!., 1982; Bystrov, 1975; Maisenbacher and Kovar, 1992a).

Other Compounds Additional compounds include choline, carotenoids (lutein, luteoxanrhin, violaxanrhin, cis-throllixanrhin, throll ichromone), IS-sitosterol, pectin, phlobaphene and rhodan; isovalerianic, lauric, myristic, nicotinic (0.12% in leaves), palmitic and stearic acids; amino acids, including cysteine, GABA (0.7 mg/g), glutamine, leucine, lysine, ornithine, proline, threonine; scopoletin, umbelliferone, vi tamin C, xanthones (1.28 mg/ 100g), and tannins (3-16%) (Benigni eta!., 197 1; Bennett and Lee, 1989; Costes and Thomas, 1967; Karryev and Komissarenko, 1980; H ansel eta!., 1993; Nahrstedt and Butterweck, 1997 in press).

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11 Figure 2: Primary compounds of H. perforatum

Naphthodianthrones (<0. 7-075%)

Hypericin (0 02-2 5%) Pseudohypericin (ca. 0.04-3 6%)

H

H

OH 0 OH OH 0 OH

OH

H OH

Flavonol G/ycosides {2-4%) R=H Quercetin R=a-1-rhamnosyl Ouercitrin R=G,-D-glucosyl lsoquercitrin Ph/orog/ucinols R=G,-D-galactosyl Hyperoside R=HL Hyperforin (2.0-4.5%)

R=G,-rutinlosyl Rutin R=CH 3: Ashyperforin (0.2-1 .9%)

Table 6: Activity of Constituents

Constituent Activity

Amentoflavone Antiinflammatory, antiulcerogenic (Berghofer and Holzl, 1989) (13', 118-biapigenin)

GABA Sedative (Nahrstedt and Butterweck, 1997, in press)

Hyperforin Antibacterial aga inst gram-positive bacteria, wound-healing (Bystrov, 1975; Gurevich eta/., 1971; Maisenbacher and Kovar, 1992a); neurotransmitter inhibitor (Nahrstedt and Butterweck, 1997, in press); potential anticarcinogenic (Oittmann eta/., 1971)

Hypericin Antiviral (Lavie eta!., 1995; Meruelo eta!. , 1988; Weber eta/., 1994)

13, 118-biapigenin Probably sedative (Berghofer and Holzl, 1989)

2-methyl-butenol Sedative (Nahrstedt and Butterweck, 1997 in press)

Proanthocyanidins Antioxidant, antimicrobial, antiviral, vasorelaxant (Nahrstedt and Butterweck, 1997, in press)

Pseudohypericin Antiviral (Meruelo eta/, 1988)

AMERICAN Ouercitrin In vitro MAO inhibiting activity (Sparenberg eta/., 1993) H ERBAL P HARMACOPOEIA'"" Xanthones Antidepressant, antimicrobial, antiviral, diuretic, cardiotonic, MAOA inhibitor (Holzl eta/., 1989; Kitanov and Blinova, 1987; Nahrstedt and Butterweck, 1997, in press; Sparenberg eta/., 1993) ST. j OHN'$ WORT M ONOGRAPH

12 ANALYTICAL The primary compounds of interest as marker co nstituents include two naturall y occurring pigments, hypericin and pse udohyperi cin (naphthodianthrones). These co mpounds are characteristic markers for this genus and are ex tracted in methanol. They both abso rb visi ble light with a max imum absorption at 588 nm and are highly fluorescent in methanol when exposed to UV light. Both pigments are similar in their absorption and emiss ion spectra, including their absorptivity. Separation of these two pigments is necessary to determine the concentration of each pigment. Flavo noids are al so considered an important class of constituents in Hypericum. Methods are provided for both classes of compounds.

H. perforatum ca n be differentiated from adulterants by the presence of hyperforin and rutin, which are absent or negligible in other species. Adulteration can also be detected through thin-layer chromatography analysis. H. barbatum is distinguished by characteristic red-orange fluorescing fl avonoid glycosides; H. hirsutum can be distingui shed by the prese nce of the compound orientin; H. montanum contains a turquoise fluorescing vegetable acid (in addition to chlorogenic acid); and only H. macufatum and H. tetrapterum contain emodin (Berghofer and Holzl, 1986).

Thin Layer Chromatography (TLC) (hypericin/pseudohypericin) Sample Preparation An extract of hyperi cin is prepared from a represe ntative sample of dried plant material. Mix 1.0 g of the dried sa mple material with 10 mL of methanol and agitate for 5 minutes. The li quid portion is decanted into a 50 mL volumetric flask. This process is repeated three more times with separate I 0 mL vo lumes of methanol. The entire contents of all four extractions are diluted to 50 mL in a vol umetric fl ask. This solution is filtered through a 0.45 Jl.m PTFE filter prior to anal ys is.

Standard Preparation Synthetic hypericin standard (ICN Biochemical, C leveland, OH, Car# 193423) is dissolved in pure methanol at a concentration ofO.lO mg/mL and filtered through a 0.45 J1.m fi lter.

Stability ofStandards/Sample Solutions Both hyperi cin and pseudohypericin pigments, as well as solutions prepared from them, are extremely stable for months if protected from li ght and refri ge rated.

Spot Test A small spot of rh e above extracts on filter paper will ex hibit bright red fluorescence under UV-365 nm light. The liquid extract solutions also flu oresce bright red under UV-365 nm li ght.

Chromatographic Conditions a. Stationary Phase: Si li ca Gel (e.g. Eastman #6060-13 181 with or without fluorescent indicator) b. Mobile Phase: Toluene-ethyl acetate-glacial acetic acid (3:6: 1) c. Sample Application: 1-5 ~ v ia capill ary d. Development: None e. Detec tion: UV-365 nm light; hypericin pigments flu oresce bright red f. RfValues: H yperi cin : 0.71 Pse udohypericin: 0.50 g. Detection Limits: 0.2 j.tg

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13 High Performance Liquid Chromatography (HPLC) (flavonoids/naphthodianthrones) Sample Preparation For crude extracrs, add 1.0 mg of eriodicryol inrernal srandard ro 100-200 mg of exrracr and dissolve inro 10.0 mL of merhanoi/DMSO (9/1).

Standard Preparation Prepare separare srock solurions of chlorogenic acid, rurin, hyperoside, isoquercitrin, quercirrin and quercerin ar a concenrrarion of 4 mg/mL. Dilure ro a l 0 mL final volume, 750 ~ , 500 ~ , 250 ~, 200 ~ , 100 ~,50~ and 25 ~ aliquors of each srock solurion. Prepare a mixed srock solurion of hypericin and pseudo hypericin, borh ar a concenrrarion of0.2 mg/ mL. Dilure ro a 10 mL final volume, 3000 ~ , 2500 ~, 2000 ~ , 1500 ~ , 1000 ~, 750 ~and 500 ~ aliquors of rhe hyperi cin /pseudohypericin srock solurion. Prepare a srock solurion of hyperforin ar a concenrrarion of abour 0.8 mg/ mL. Dilure ro a 10 mL final vol ume, 3000 ~, 2000 ~, 1000 ~ , 500 ~ , 250 ~ and 100 ~ aliquors of rhe hyperforin solurion. Add 1.0 mg of eriodicryol (available rhrough Exrrasynrhese) ro each srandard solurion as an inrernal srandard.

Note: ALl preparations and dilutions are made using methanol/DMSO (91 1) as the solvent.

HPLC Parameters a. Column: Prosep C-18, 5 j.lm, 4.0 x 150 mm b. Temperarure: 25 ·c c. Mobil e Phases: Gradienr I: Aceronitrile II: 0.5% trifluoroaceric ac id in warer II!: Merhanol-aceroni rrile-rrifluoroaceric acid (60:39.5:0.5)

Time (min) %A o/oB o/oC 0.00 10 90 0 5.0 20 80 0 7.0 0 70 30 10.0 0 50 50 20.0 0 0 100 45.0 0 0 100 50.0 10 90 0

d. Flow Rare: 1.0 mL!min e. Derecrion: 284 nm f. Injecrion Volume: 20~, 5 ~ 0 b' Column Temperarure: 25" c

Quantitation Injecr each srandard rhree rimes. Derermine correcrion facrors, srandard deviarions, correlarion coefficiencies, and calibrarion curves based on peak area rarios using linear regression analysis.

AMERICAN H ERBAL

1 P HARMACOPOEIA "

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14 UVNIS Spectroscopic Method (hypericin/pseudohypericin) Sample Preparation A quantitative exrract is prepared by exrracting 1.0 g of powdered herb sample with three 25 mL portions of dichloromethane (CH Cl ) or until ftltrate is clear. Discard the 2 2 dichloromethane extract. Extract the dried residue exhaustively with acetone. Evaporate the acetone exrract to dryness under vacuum. Dissolve the res idue in three 8 mL portions of methanol and rransfer to a 25 mL volumerric flask . Add enough additional methanol to make the total volume 25 mL. Filter 10 mL of this solution and discard the first 2 mL. Dilute 5 mL of the filrrate to 25 mL with methanol using a separate 25 mL volumetric flask.

Figure 3: HPLC Chromatogram

1 = chlorogenic acid 2= rutin 3= hyperoside 4= isoquercitrin 5= quercitrin 6= eriodictyol (internal standard) 7= quercetin 8= 13, 118-biapigenin 9= pseudohypericin 1 0= hyperforin 11 = hypericin

8

9

10.00 20.00 30 . 00 ~0 . 00

Minutes

AMERICAN H ERBAL 1 PHARMACOPOEIA "

ST. JoHN's WoRT M o OGRAPH 15 Spectroscopic Measurement and Calculation Measure rhe absorption of the solu tion in a 1 em cuverre at 590 nm against a methanol blank. Calcul ate the rota! hypericin content (both hypericin and pseudohypericin) from the specific absorption.

I% f em = Assuming that at 590 nm A 1 870, roral hypericin content is calculated as follows:

AS90 X 125 Total hypericins (%w/w) = [sample mass (g)] x 870

Note: Where A590 is measured absorption at 590 nm and sample mass is the actual mass ofthe Hypericum sample extracted (approximately 1.0 g accurately weighed to 0.01 g) (DAC, 1986).

Quantitative Standards Foreign Maner: Nor more than 2% (DAC, 1986) Total Ash: 5% (DAC, 1986; Pharmacopoeia Helvetica, 1996) Acid Insoluble Ash: Nor more than 2.5% (Bradley, 1983) Moisture: Nor more than 12% (Benigni et al., 1971) Loss of Moisture on Drying: Nor more than 10% as determined with 1000 g of herb dried for 2 hours berween 100 and 105o C (2 12 and 22 1° F) (Pharmacopoeia Helvetica, 1996; DAC, 1986) Moisture in Fresh Flowers: 87.3% (Benigni etal., 1971) Moisture in Dried Flowers: 6% (Benigni et al., 1971) THERAPEUTICS Hypericum perforatum has been widely researched for irs antidepressant effects. Recent interest has foc used on irs potential as an antiviral agent. There is some data confirming irs traditional wound-healing effects. Hypericum contains several compounds of biological interest, including the naphrhodianthrones hypericin and pseudohypericin and a broad spectrum of flavonoids. Although investigations continue, these are considered to be primarily responsible for Hypericum's activity.

Pharmacokinetics Derailed pharmacokineric studies have bee n performed with rhe standardized Hypericum extract, LI 160 (Jarsin® 300), one of several officially recognized formulations in Germany for the treatment of mild ro moderate depress ion. It is reported ro contain 300 mg of the dried extract of Hypericum perforatum, yielding 0.24-0.32% rota! hypericin.

Oral admi nistration of this preparation was given ro rwelve heal thy male subjects (Sraffeldr et al. , 1994). Hypericin and pseudohypericin were determined in plasma using an HPLC technique (limit of detection 0.2 ng/mL) after oral administration of si ngle doses of 300, 900, and 1800 mg roral extract. Blood levels were measured for up ro three days after a single dose (Tables 7 and 8).

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16 Table 7: Pharmacokinetic parameters for hypericin after single oral doses of Hypericum extract, Ll 160*

Hypericum Extract Dose

300 mg (n = 4) 900 mg (n = 3) 1800 mg (n = 4)

AUC (ng min/mU 1920 (978-2720) 8820 (8740-11890) 23090 (12790-29020) Tmax (hours) 5.2 (4 0-6.0) 4.1 (4 0-6 0) 5.9 (5 0-6 0) Ta (hours) 2.6 (24-2.8) 2.0 (1 7-2 5) 2.6 (1.8-2 7) 1 9 c max (ng/ml) 1.5 (1 0-2.0) 7.5(6.1-125) 14.2 (8 6-19 3) 24.8 (1 0 3-37.0) 26.0 (13.0-41 0) 26.5 (21 5-40.5) T,12 (hours)

Tmax = time of maximum plasma concentration; Ta = absorptive lag; Cmax = maximum concentration; T, = half life. * Numbers are median with 19 12 range in parentheses. Doses correspond to hypencin doses of approximately 250, 750, and 1500 11g (Staffeldt eta!., 1994, reprinted with permission Journal of Geriatric Psychiatry Neurology1.

Table 8: Pharmacokinetic parameters for pseudohypericin after single oral doses of Hypericum extract, Ll 160*

Hypericum Extract Dose

300 mg (n = 4) 900 mg (n = 3) 1800 mg (n = 4)

AUC (ng min/ml) 1900 (1150-2600) 7130 (4800-9870) 19910 (15420-23740) Tmax (hours) 2. 7 (2.0-3.5) 3.0 (3 .0-3 5) 3.2 (2.0-4 0) Ta (hours) 0.6 (0.4-0.8) 0.4 (0.3-0 6) 0.4(03-1 .1) 1 9 c max (ng/ml) 2.7 (2 0-5 4) 11.7 (9.4-15.0) 30.6 (23 0-35.8) T, (hours) 16.3 (6 3-30.5) 36.0 (18.0-42.0) 22.8 (9 0-34 5) 12

Tm" = time of maximum plasma concentration; T1a = absorptive lag; Cmax = maximum concentration; T,12 = half life. * Numbers are median with range in parentheses. Doses correspond to pseudohypericin doses of approximately 526, 1578, and 3156 119 (Staffeldt eta/., 1994, reprinted with permission Journal of Geriatric Psychiatry Neurology).

Peak plasma concentrations were seen wirh hypericin after 2.0 ro 2.6 hours and with pseudohypericin between 0.4 and 0.6 hours (Tables 6 and 7). Peak concentrations of hypericin were 1.5, 7.5 and 14.2 ng/mL, respectively, for the rhree doses of the exrracr. Pseudohypericin arrained concentrations of 2.7, 11.7 and 30.6 ng/mL, respectivel y. The elimination half-l ife of hypericin was between 24.8 and 26.5 hours. The elimination half-life of pseudohypericin ranged from 16.3 ro 22.8 hours.

Repeated doses over 14 days (3 x 300 mg/day) resulted in steady srare (level ar which rhe constituents accumulate ro reach a steady concentration) afrer four days. The peak concentration for hypericin was 8.5 ng/mL and 5.8 ng/mL for pseudohypericin. Trough concentrations (14 hours afrer rhe last dose) were between 5.3 and 3.7 ng/mL for borh compounds (S raffeldr eta/., 1994). (Table 9).

Earli er pharmacokineric clara on mice report rhar maximum plasma concentrations of hypericin and pseudohypericin were reached ar 6.0 hours and maintained for ar least 8.0 hours. T he aqueous-erhanolic exrracr used contained 1.0 mg of hypericin. The same researchers also rested rhe concentration of hyperici n in one human resr subject afrer a single dose of rhe same exrracr. The concenrrarions found in human serum were

comparable ro rhose fou nd in rhe mice (Srock and Holzl, 1991) (Table 10). AMERICAN H ERBA L 1 PHARM ACO POEIA "

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17 Table 9: Pharmacokinetic parameters after repeated oral doses of Hypericum extract, Ll 160*

Hypericin Pseudohypericin

Cmax (ng/mL) 8.5 5.8 Cbasal (ng/mL) 5.3 3.7 T 112 (hours) 28.0 23.5

C = maximum concentration; Cb , = basal concentrati on; T,12 = half life. • Numbers are mean of n = 2, 14 days of 3 x 300 mg (Staffeldt et ar"x1994, reprinted wi th permi ssio;\''Jouma/ of Geriatric Psychiatry Neurology).

Table 10: Amount of radioactivity in % of the total activity found in all organs and excrements of mice administered hypericin and pseudohypericin

Time in hours (h) Substance GIT Liver Kidney Muscle Blood Brain

1.5 h H 41 .95 0.50 0.67 30.64 5.51 0.67 PH 69.34 1.17 0.40 2.80 1.60 0.43

3.0 h H 58.18 0.67 0.47 13.04 1.44 0.58 PH 59.51 1.04 0.66 2.87 3.21 0.13

4.5 h H 59.48 0.62 0.58 4.58 2.69 0.25 PH 67.44 1.41 0.27 4 .74 5.11 0.01

6.0 h H 18.51 2.73 0.65 11 .30 7.42 0.58 PH 43.62 1.92 0.98 10.88 5.94 0.93

H = hypericin; PH = pseudohypericin; GIT = gastrointestinal tract. Modified from Stock and Hiilzl, 1991

Pharmacodynamics Clinical Studies Hypericum has become increasingly popular in Germany, where physicians routinely prescribe herbal medicines. In 1994, 66 million daily doses of Hypericum perforatum were prescribed there for use in the treatment of depression (DeSmet and Nolen, 1996). This phytomedicine has been tes ted in more than 3,000 patients against placebo and various active medications (Hansgen et al., 1994; Harrer et al., 1994; Hubner et al., 1994; Sommer and Harrer, 1994; Vorbach et al., 1994; Wolk et al., 1994).

German researchers along with a colleague from San Antonio, Texas, recently published a meta-analysis of23 randomized trials of Hypericum with a total of 1,757 outpatients with mild to moderately severe depressive disorders. They concluded that the herb was significantly superior to placebo and appeared comparably effective to standard antidepressants (maprotiline, imipramine and amitriptyline) while producing fewer side effects (Linde et al. , 1996). The preparations used were all standardized to hypericin content (Table 11 ).

The controlled studies of Hypericum's efficacy in depression included in the above­ mentioned meta-analysis were randomized, or "quas i-randomized" through alternation. Comparisons were made of the herb alone, or in combination with other plant extracts, to placebo, and/or a standard antidepressant. Twenty of the 23 trials were double-blind, one AMERICAN was single-blind, and two were open label. Most were 4 to 8 weeks in duration. The H ERBAL methodological quali ty of each study was assessed by at least two reviewers to determine

P HARMACOPOEIATM eligibility for inclusion in the meta-analysis.

ST. JoHN's WoRT MONOGRAPH

18 Table 11: Description of the Hypericum preparations used in the depression studies reviewed by Linde et a/., 1996

Preparation Name Total Extract/Day Total Hypericin/ Da y

Esbericum NA 0.75 mg Extract Z 90017 500-1000 mg 1-2 mg Hyperforat NA 0.4-0.6 mg Jarsin (tablets) 900 mg 1.08 mg Jarsin 300 (tablets) 900 mg 2.7 mg Neurapas 600 mg 0.48 mg Neuroplant (caps) 500 mg 1 mg Psychotonin M®(drops) 350-500 mg 0.5-0.75 mg Sed ariston * 300-600 mg 0.45-0.9 mg

*Also contains valerian extract; NA = no information available.

In each study, improvement in depressive symptoms had been evaluated with depression scales with interrarer reliabiliry, most commonly the Hamilton depression scale (HAM-D) and the clinical global impressions index (CGI). The daily dose of either hyperici n, the reference subsrance for standardization, or of total extract varied consider­ ably between studies, from 0.4 to 2.7 mg and 300 to 1000 mg, respectively.

In 13 studies comparing a si ngle Hypericum preparation with placebo, 55.1 percent (225) of patients receiving the herb improved, compared with 22.3 percent (94) respond­ ing to placebo. In the comparisons to standard antidepressants in three trials with single preparations and two with combinations, 63.9 percent (101) of patients responded to single preparations compared with 58.5 percent (93) to standard antidepressants and 67.7 percent (88) responded to combination extract products (Hypericum and Vaferiana) compared with 50 percent (66) to standard antidepressants.

The researchers acknowledged the problems in drawing valid conclusions from the pooled data of quite heterogeneous studies. These problems are compounded by the different amounts and preparations of rhe herb used across the studies (Table 11) and the possibiliry that hypericin is nor the only active component.

These limitations as ide, Linde and coll eagues find sufficient evidence to conclude that Hypericum is better than placebo in treating some depressive disorders. These data were inadequate, however, to judge yet whether it is as effective as standard antidepressants, although ir appears to cause fewer side effects. They consider rhar these initial indications of efficacy warrant the undertaking of longer controlled trials comparing several doses of different Hypericum preparations to standard antidepressants.

In separate commentary accompanying the meta-analysis, Netherlands researchers Peter De Smer and Willem olen agree that these data are promising, but not yet suffi­ cient to accept Hypericum as an effective antidepressant preparation (De Smer and Nolen, 1996). Aside from the need for dose standardization and adequate trial lengths, they call for studies in severely depressed patients and long-term studies to assess the risk of relapse and emergence of late side effects (De Smet and Nolen, 1996).

Animal Studies A commercial standardized extract of Hypericum perforatum (Psychotonin®) was tested in several animal models predictive of psychotropic activiry (Okpanyi and Weischer, 1987). AMERICAN These activities included two used for antidepressants: increased acriviry in a water wheel H ERBAL rest in mice and reduced aggressiveness in isolated male mice. PHARMACOPOEIA""'

ST. JoHN's WoRT M ONOGRAPH

19 In a recent presentation, Butterweck et al., (1996, 1997 in press) compared the Hypericum ex tract, LI 160, with bupropion, a sy nthetic antidepressant. The authors found that both drugs res ulted in similar effects, including the rail suspension rest (mice) and the forced swim rest (rats). Since Hypericum treatment was antagonized by drugs known to reduce dopamine functional acti vity (haloperidol, sulpiride, a-merhyltyrosine, and g­ butyrolactone), the authors co ncluded that Hypericum exerts its activity via dopaminergic activation. Studies on va rious fractions of the methanol extract revealed that different constituents were responsible for the various acti vities .

Muller eta!., (1996) reported rh ar the Hypericum extract, LI 160, res ulted in a 15% down-regulation of g-adrenergic receptors in the rat frontal cortex after subchronic treatment (250 mg/kg for 2 weeks). In rhe sa me study, these authors found a 25% down­ regulation after similar doses (10 times the clinical dose) of imipramine.

In Vitro Studies Whil e previous studies report that hypericin inhibits MAO at concentrations of 50 11g/mL (e.g., Suzuki eta!., 1984), others have failed to co nfirm this effect (B iadr and Wagner, 1994; Demisch et al., 1989; Thiede and Walper, 1994). One explanation is that the hypericin used by Suzuki was apparently an extract of only 80% purity. It is poss ible that one or more constituents of the remaining 20% of this preparation could account for this weak enzyme inhibition. This possibility is supported in a paper by Bladr and Wagner (1994) who report rhar rhe Hypericum fractions with the greatest MAO inhibition contain the highes t conce ntration of Aavonoids. Computer modeling of Hypericum constituents also sugges ts Aavonoids to be the most likely MAO inhibitor fraction, due to a structural similarity to toloxotone and brofaromine, two known inhibitors of MAO A( H oltje and Walper, 1993). In another study, the xanthone fraction was found to be a particularly strong inhibitor of MAO A in vitro (S parenberg et al., 1993).

H owever, the MAO inhibition shown for Hypericum may not be pharmacologically rel evant since it has not yet been confirmed in vivo. Bladt and Wagner ( 1994) reported that no MAO inhibition was seen ex vivo after administration of 300 mg/kg Hypericum extract to rats. Whether this is due to a rapid metabolism of the active constituents, or to other reasons, cannot be determined with certainty at this point. Pharmacokinetic studies with the Hypericum extract, LI 160, showed plasma levels of only 1.5 ng/ mL of hypericin after a single 300 mg dose and 8.5 ng/mL at steady state in human volunrecrs (Staffeldt et a!., 1994). Unless the active compounds are present in much larger quanriries than is hypericin, or are concentrated in synaptic terminals, these blood levels are several orders of magnitude below the concenrrarions needed to inhibit MAO. Inhibition of another degradative catecholamine enzy me, carechol-o-methyltransferase (COMT), can also be seen with various ethanolic Hypericum fractions at super-phys iologic concentrations of up to 500 11g/ mL (Thi ede and Walper, 1994).

Other proposed mechanisms involve effects on serotonin. Muller and Rosso! (1994) report that Hypericum extract inhibits serotonin receptor expression at 50 1-J.M (~25 11g/mL (according to the way these authors use the term "molarity" when referring to a crude extract) and Perovic and Muller (1995) reported inhibition of serotonin uptake (IC = 6.2 50 11g/mL). T he conce ntration required for the former effect could surely neve r be achieved in the whole animal and even the latter concentration seems unlikely. As a reference compari­

so n, Muller et a/.,(1996) reported an !C50 for the synthetic antidepressanr, clomipramine, of 0.9 nM (~0.3 ng/mL) for serotonin uptake inhibition. In addition, Muller et a/.,(1996) = recently reported an inhibition of both synaptoso mal GABA uptake (IC50 1 11g/mL LI = 160) and GABAA-receptor binding (IC50 3 11g/mL).

AMERICAN H ERBAL PHARMACOPOEIA ,."'

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20 Table 12: Receptors showing significant binding by Hypericum perforatum crude extract

Extract Concentration (IJ.g/mL) % Inhibition in Various Assays

Adenosine GABAA GABAB 5HT1 BDZ IP3 MAOA MAOB

0.005 -2 7 45 12 -4 -3 9 -1 0.05 13 43 85 12 0 16 4 -10 0.5 17 94 105 9 0 13 33 -2 5.0 20 100 109 12 19 40 97 53 50 71 101 114 54 65 107

-K, (IJ.g/mU* 0.075 0.006 25 24 10 2 3.2

* K, = IC 5J 1 + ligand affinity/ligand concentration

Another novel proposal is rhar Hypericum ex tract (concentration nor provided) reduces cytokine expression (interl eukin-6) (Thiele eta!. , 1994). The hypothesis is that inrerleukins can induce depression in susceptible individuals (Smith, 1991 ). The field of psychoneuroimmunology is perhaps too new to give a definitive answer regarding this mechanism in rhe near future, bur rh e link berween depress ion and rhe immune system is still drawing attention (Kook et al., 1995).

Through an NIMH screening contract (NovaScreen®, Baltimore, Maryland) a commercially available crude extract from the fres h flowers and buds of Hypericum perforatum (1: 1.5; hydro-alcohol [40:60] made from fl owering tops; H erb Pharm, Williams, OR) containing ~ 0 .1 o/o hypericin was dried under vacuum, dissolved in 4% DMSO and diluted to an initial concentration of 5 g/mL for in vitro assays in a battery of 39 receptor types and rwo enzyme systems. The receptor assays showing at least 50% displacement of radioli gand (o r 50% inhibition of MAO) were considered "hits." ) Concentration-response curves (IC50 were then performed for rhe hits.

Table 13: Receptor binding/enzyme inhibition by hypericin

Drug cone. (IJ.M) % Inhibition

MAOA MAOB NMDA

.001 10.5 .01 24.5 .1 -0 .3 1 48.5 10 27 .0 -2.0 81.7 100 20.8 -20.7

-K 1 .1

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21 The crude extract of Hypericum had significant receptor affinity for adenosine, GABAA, GABA , serotonin, benzodiazepine, inositol triphosphate (IP), and monoamine 8 ) oxidase (MAO A. 8 (Cott and Misra, 1997 in press) (Table 12).

The inhibition of MAO by crude Hypericum extracts is consistent with previous reports (B ladr and Wagner, 1994; Suzuki et al., 1984; Thiede and Walper, 1994). Unlike

the crude extract, however, synthetic hypericin (95%) lacked sign ificant MAOA or MA08 inhibition at concentrations up to 10 !JM (Table 13). Hypericin had affinity onl y for NMDA receptors (K, ~ 1 !JM) and this may play a role in irs reported antiviral activity since NMDA antagonists prevent gp120-induced neurotoxicity (Diop etal., 1994).

These data are consistent with recent pharmacologic evidence suggesting that other constituents of this plant may be more important for the reported psychotherapeutic activity. Some of these results have been previously reported (Corr, 1995; Cort, 1996; Cart , and Misra, 1997, in press). With the exception of GABAA and GABA8 the concentrations of Hypericum extract required for these in vitro activities may not be attained after oral administration in whole animals or humans. It is conceivable that the very high affinity of Hypericum extract for GABA receptors presented here may be important. Future studies should characterize Hypericum's effect with greater sophistication to determine if and how GABA receptors are affected in whole animals. Plasma levels suffi cient to bind GABA receptors would be predicted unless the responsible components are metabolized before they enter rhe ge neral circulation; however, studies of intrinsic activity (agon ist or antago­ nist) have not been done. Additional studies of pharmacologic mechanism(s) of the individual constituents must be co nducted so that standardization can be performed on the appropriate constituent for the intended purpose. It should be noted that Mi.iller et al.,

(1996) reported an IC50 of3 11g/mL for GABAA. The reason for this difference between this IC and the values listed in Table 12 is nor known. 50

The signifi cance of this GABA binding is unknown at the present, bur there is considerable literature on the role of GABA in affective disorders. GABA stimulation has 8 been found to enhance receptor down regulation during imipramine treatment (Enna et al., 1986). Nielsen et al., ( 1990) have reported antidepressant effects with the GABAergic agent, fengabine, in depressed outpatients. Petry et al., (1992; 1993) have reported that GABA plasma levels are low in both bipolar and unipolar depression and that benzodiaz­ epines, which enhance GABAA activity, may be effective antidepressants as well as anxiolyrics (Perry et al., 1995). GABA neuronal systems also modulate dopamine and dopamine-induced behaviors (Cor et al., 1976; Corr and Engel, 1977).

Antiviral Activity Hypericin is currently in early clinical trials in the United States as an antiviral (Bombardelli and Morazzoni, 1995; Meruelo et al., 1988). In one open pilot study, 18 patients with acquired immune deficiency syndrome (AIDS: classifications; 3 with CDC II, 8 with CDC III, 4 with CDC IVB and 3 with CDC IVCl) were treated with an i.v. Hypericum preparation (Hyperforar; 2 x 2 mL weekly) plus additi onal Hypericum tablets of undefined dosage. Sixteen our of 18 with good study compliance showed stable or in creasing counts of absolute CD4 val ues over a 40-month period. Also observed were improvements in CD4/CD8 ratios in the majority of patients. In addition only 2 of the 16 patients experienced an opportunistic infection during rhe 40-month observation period. The other 14 of the 16 patients remained clinically stable (Karnovsky-Index of 100) (Steinbeck and Wernet, 1993). However, it has not yet been determined if these same effects can be expected with oral administration.

Studies have shown that two of Hypericum's primary components, hypericin and pseudohypericin, inhibit a variety of encapsulated viruses, including herpes simplex types 1 and 2 (Weber et al., 1994; Wood et al., 1990) and the human immunodeficiency virus

AMERlCAN type 1 (HIV-1) virus associated with AIDS (Lavie et al., 1989; Lopez-Bazzocchi et al., HERBAL 1991; Meruelo et al. , 1988). While the later researchers have concluded that hypericin and

PHARMACOPOEIA TM pseudohypericin display a unique and uncommonly effective antiviral activity, Weber et al., (1994) suggest that it may be due to nonspecific association with cellular and viral

ST. JoHN's WoRT membranes. MoNOGRAPH

22 In vitro antiviral activity has also been reported against murine cytomegalovirus, para-influenza 3 virus, Sindbis virus (Lopez-Bazzocchi et al., 1991 ), vesicular stomatitis virus (Wood et al., 1990), and equine infectious anemia virus (Carpenter and Kraus, 1991 ) {Tables 14 and 15).

The antiviral activity appears to involve a photoactivation process {Carpenter and Kraus, 1991; Degar et al., 1993; Hudson et al., 1991 ; Kraus et al., 1990; Lopez-Bazzocchi et al., 1991) which forms singlet oxygen and inactivates viral fusion and syncytia formation (Lenard et al., 1993; Thomas et al. , 1992; Yip et al., 1996). While hypericin does show antiviral activity in vivo (mice), these photodynamic properties may limit its potential usefulness as an antiretroviral agent (Stevenson and Lenard, 1993). However, besides singlet oxygen production, hypericin can photo reduce oxygen to superoxide radicals and can form semiquinone radicals in the absence oflight {Lavie et al. , 1995). These later authors speculate that this ability to form semiquinones might account for the antiviral activity in the whole animals and they have maintained si nce the early 1980's the clinical utili ty of hypericin.

Protein Kinase C Inhibition Hypericin has been reported to inhibit the growth of glioma cell lines in vitro and to be a potent inducer of glioma cell death due to inhibition of protein ki nase C {PKC) as measured by [3H] thymidine uptake. In this regard the glioma inhibitory activity is to to reported be equal or greater than Tamoxifen (IC50 values of< 10 versus 10 f.Lmol!L) and additionally was reported to be increased by approximately 13 o/o upon exposure to visible light (Couldwell et al., 1994). T he anti-PKC activity doses are reported to be below those associated with clinical hypericism {Couldwell et al., 1994).

Table 14: Concentration (!lg/ml) to achieve a 1 log10 reduction in virus titer HSV-1 HSV-2 Para-3 w vsv

Hypericin 0.2 << 0.1 0.1 < 0.1 Emodin > 10 > 10 > 10 > 10 > 10 Emodin anthrone > 10 > 1 > 10 > 10 >8 Emodin bianthrone << 1 << 1 4 >50 << 1

HSV-1 & 2 = herpes simplex viruses 1 & 2; Para-3 = parainfluenza virus type-3; W = Vaccinia virus; VSV = vesicular stomatitis virus. Modified from Wood et at., 1990.

Table 15: Antiviral activity (plaque reduction) against HCMV, strain AD-1669, in MRC-5 cells

E05 0 f.ig/ mL CD50 fl 9/ mL Tl

Hypericin 0.8 1.2 1.5 Emodin 1 .1 2.6 2.4 Emodin bianthrone 0.6 1. 1 1.8 Rhein 1 .1 3.4 3.1

HCMV = human cytomegalovirus; ED50 = effective dose for 50 % plaque reduction; CD 50 = cytotoxic dose resulting in 50 % cellular . toxicity; Tl = therapeutic index = CD 5ofED 50 Modified from Wood et at., 1990.

AMERICAN H ERBAL

PHARMACO POEIA TM

ST. JoH N's WoRT MONOGRAPH 23 Other researchers report a PKC-inhibiring acriviry with both hypericin and

pseudohypericin (IC50 of 1.7 11g/mL and 15 11g/mL, respectively) (Takahashi et al., 1989). Receptor ryrosine kinase activiry of epidermal growth factor has also been reported to be inhibited by hypericin (de Witte et al., 1993). These later effects have been linked to both the antiviral and antineoplastic activities (Lavie et al., 1995; Panossian et al. , 1996). In addition, the PKC inhibition may also contribute to the anti-inflammatory effects historically associated with Hypericum as hypericin has been found to inhibit the release of

arachidonic acid and leukotriene B4 (Panossian, 1996).

Wound-Healing Effects Hypericum has historically been one of the most relied upon botanicals for the treatment of wounds. Parr of this acriviry is due to Hyp ericum's anti-microbial activiry, which is attributed to the essential oil, phloroglucinols, and fl avonoids. The essential oil and the water soluble fraction of an alcoholic extract exhibit minor antifungal and significant antibacterial acriviry. A resin fraction of the alcoholic extract has also been shown to be effective against gram-positive organisms (Gaind and Ganjoo, 1959). The tannins and flavonoids were reported to inactiva te Escherichia coli at dilutions of 1:400 or 1:200 (Khosa and Bhatia, 1982; Shakirova et al., 1970). Hyperforin and adhyperforin have been reported to possess an antibiotic effect greater than that of sulfonilamide (Negrash and Pochinok, 1972).

A burn ointment prepared by extracting 5 g of fresh fl owers with 100 g of olive oil for 10 days at 20° C (68° F) was used in the treatment of 1st, 2nd, and 3rd degree burns. First degree burns healed in 48 hours. Second and third degree burns healed at least three times as rapidly as burns treated with conventional methods and keloid formation was inhibited (Saljic, 1975). A commercial preparation co ntaining 0.412% quercirrin (Novoimamin) was found to be effective aga inst Staphyloccus aureus infection (Negrash and Pochinok, 1972). In this regard, irs effects have been reported to be greater than conven­ tional treatment with sulfonilamide (Aizenman, 1969).

A tincture (1 :10) of Hypericum was studied for its wound-healing properties and compared with Calendula, another widely used wound-healing herb. The effect of orally administered tincture of Hypericum was more pronounced than topical application of Calendula tincture in the healing of incision, excision and dead space wounds, as evidenced by an increase in epirhelisarion and wound-breaking strength (Rao et al., 1991) (Table 16).

Other Effects Hypericum has bee n reported to have a number of additional effects. In one study the procyanidin (PC) fraction of Hypericum was rested in an isolated guinea pig heart prepara­ tion (Melzer et al., 1989) and found to enhance coronary flow in the same way as the procyanidins from Crataegus (hawthorn). The same researchers tested the procyanidin fractions in porcine isolated coronary arteries. All PC fractions antagonized histamine or prostaglandin F a-induced arterial contractions (Melzer 1991). 2 et al.,

In another study, a significant increase in the production of nocturnal melatonin was observed (P< 0.05) after administration of 90 drops of the commercial preparation H yperforat. These effects were observed after a three week period (Demisch et al. , 1991 ). Other researchers report that Hypericum may be useful in the treatment of chronic tension headaches (Heinze and Gobel, 1996), while a hepatoprotective activiry of a water/alcohol extract has also been reported in animals (500 mg/kg/i.p.) . This conclusion was based on

the abiliry of Hypericum to increase bile duct flow in rats and to reduce CC14-induced necrosis in barbiturate treated mice (Ozti.irk et al., 1992).

AMERICAN H ERBAL PHARMACOPOEIA"'

ST. ] OHN's W o RT M ONOG RAPH

24 Table 16: Effects of the tinctures of Hypericum and Calendula on wound-healing

Wound model - Incision Excision Dead space

Parameters Breaking Epithelisation % Wound contraction by day Granuloma studied strength (g) period (days) 5 10 15 weight (mg)

Controls 270.0 ± 22.1 23.00 ± 1.0 50 0 ± 2.1 70.0 ± 1.2 90.0 ± 0.4 57.0 ± 4.50

Hypericum (oral) 396.0± 18.5** 15.00 ± 0.3* * 45.0 ± 1.2 88.0 ± 1.0 95.0 ± 1.0 55.3 ± 3.20

Calendula (topical) 351 .0± 13.5* 16.50 ± 1.0** 40.0 ± 2.1 74.0 ± 0.8 99.0 ± 0.5 -

n (number of rats per group) = 7; * P< 0.01; * * P< 0.001 (Rao, eta/, 1991 reprinted with permission of Fitoterapia)

Conclusion Hypericum is clearly one of the leading psychotherapeutic phyromedicines for rhe rrear­ ment of mild ro moderate depression. The shorrcomings of the currenr conrrolled clinical trials of Hypericum have been poinred our in the review by Linde et al., ( 1996) and by Ernst (1995). They include lack of well-characterized severely depressed parienr popula­ tions, heterogeneity of diagnoses, lack of inrent-ro-rreat analyses, lack of long term studies, lack of conrrol over compli ance, and low dosages of comparison medications.

The lack of a clearly definabl e pharmacologic mechanism is nor unlike many other psychotherapeutic agents and is therefore nor particularly problemati c. However, conrinued research is needed ro idenrify rhe constituents most res ponsible for Hypericum's activity so that preparations can be optimally standardized. The currenr procedure of standardizing according ro hypericin conrenr appears ro result in an active product and may be better than no standardization. While determining the pharmacological profile of all major componenrs of Hypericum will be a difficult task, it will surely add ro rhe body of knowledge regarding rhe biochemistry of depression.

Actions Internal: The most well documented activities of Hypericum and its derivatives is as an antidepressant and wound-healing agenr. Additional actions associated with inrernal use include anti-inflammarory (Panossian, 1996), anriviral (La vie et al., 1989; Meruelo et al., 1988; Yip et al., 1996), astringent (Bradley, 1983), cardioronic (Melzer et al., 1989; Melze r etal., 1991) and sedative (Bradley, 1983).

External: T he most well documented activities of Hypericum are as an analgesic, anri-inflammarory, antimicrobial, and vulnerary (Blumentha et al., 1997; Bradley 1983) .

Indications Internal: Hypericum is predominantly used for the rrea tment of mild ro moderate depres­ sions. It has been suggested ro be useful in the treatment of more severe forms of depression, but controll ed clinical trials are lacking. In addition, its effecti ve ness in long­ t e rn~ therapy is not known. As with conventional antidepressants, therapeutic effects are not ro be expected before 2-3 weeks of therapy.

In addition ro the antidepressant effects, Hypericum has hisrorical ly been used for a wide variety of neurological conditions, including anxiety, inso mnia due ro restlessness, irritability, neuralgia, trige minal neuralgia, neuroses, migraine headaches, fibrositis,

dyspepsia {oil), and sciatica {Blumenthal et al., 1997; Bradley, 1983; ESCOP, 1996; A !v1ERICAN Hahn, 1992). H ERBAL 1 P HARMACOPOEIA "

ST. JoHN's WoRT M oNOGRAPH 25 Other types of pain and inflammation of nerve origin may also respond to Hyperi­ cum which can be administered both topically and orally (Boericke, 1927*; Felter, 1922; Priest and Priest, 1982). These indications include pain and inflammation surrounding a painful tooth socket following tooth extraction (Priest and Priest, 1982), herpes zoster (shingles), herpes communis (Halm, 1979), chro ni c neuralgia stemming from fractures, spinal injuries, musculoskeletal trauma, surgical trauma (Boericke, 1927*; Felter, 1922), nerve injury resulting in lancinating, burning or ringling pains and twitching or spasm following a traumatic injury (Boericke, 1927*; Priest and Priest, 1982).

*Although taken from homeopathic literature, the preparations specifically used (1 : 10 tincrures) are relatively consistent with those used in modern herbal therapy.

Hypericum has also been widely used for enuresis due to nervous anxiety or nerve irritation in the bladder especially in children (Weiss, 1988), and as a specific for menopausal neurosis (Bradl ey, 1983).

Hypericum oil and infusion have been used clinically for gas tric conditions, includ­ ing gastric ulcer and functional gastritis (Krylov and Ibatov, 1993), nervous dyspepsia, inflammatory bowel syndrome and internal hemorrhoids. For inflammatory bowel syndromes the oil is best administered as an overnight retention enema (Hahn, 1992).

In recent years, Hypericum and its va rious derivatives have been used by many people as an antiviral agent in the self treatment of HIV/AIDS. However, objective data regarding its usefulness are lacking Uames, 1990).

Topical: Various external preparations are used, including the oil, infusion, co m­ press, and gels and salves. Of these, the oil macerate is the most widely used. Oil: Bites, bruises, burns, frostbite, hemorrhoids, herpes les ions, lacerations, myalgia, scrapes, sunburns, non-healing and painful ulcers, urticaria (Blumenthal et al., 1997; Bruneton, 1995; Ellingwood, 1919; H alm, 1979). Infusion: Astringent mouthwash and gargle for pain of the oral cavity. Compress: Bites, bruises, enlarged glands, puncture wounds, swellings. Gels and salves: Anti-inflammatory and vulnerary properties (Bombardelli and Morazzoni, 1995).

Caution: Care should be taken when using external preparations in conjunction with therapies utilizing ultrasound or ultraviolet light (see co nrrai ndicarions and side­ effects).

Dosages Powder*: 2-4 g (DAC I 0, 1986) Infusion*: 1-2 cups two times daily corresponding to approximately 2-4 g herb (H ansel et al., 1993) Tincture (1 :5)*t: 2-4 mL three times daily (B radley, 1983; H ansel et al., 1993) Fluid Extract (1:1): Equi valent of 0.5-3.0 mg total hypericin daily Powdered Extracts: Eq uivalent of0.5-3.0 mg total hypericin daily Oil: I tsp. on an empty stomach (for gastric complaints) morning and eve ning (Hahn, 1992)

* Or equivalent to 0.5 to 3.0 mg of hypericin daily t An extract strength range of 4:1 to 7:1 has been recommended (Hansel et al., 1993).

AMERICAN H ERBAL PHARMACOPOEIA.,."

ST. JoHN's W oRT M oNOGRAPH 26 Contraindications Slight in vitro uterotonic effects have been reported in animal models suggesting that Hypericum should be used with caution in pregnancy (Shiplochliev, 1981). Because of its potential as a photosensitizing agent, it is suggested that therapeutic ultraviolet treatment be avoided when using Hypericum.

Notice: Tyramine-containing foods and selective serotonin reuptake inhibitors such as Prozac® are contraindicated with MAO inhibitors. However, reports of in vivo MAO inhibition with Hypericum are lacking. Considering its widespread use throughout Europe and a lack of reported side-effects in numerous human studies, it is unlikely that negative interactions with these substances will occur with Hypericum use.

Side Effects Photosensitization in fair-skinned people has been demonstrated in a controlled clinical trial involving metered doses of hypericin and exposure to ultraviolet UVA/UVB irradiation (Roots eta/., 1996). Using the LI 160 preparation (0.24-0.32% total hypericin), a measurable increase in erythema in light-sensitive volunteers receiving 600 mg three times daily for 15 days with UVA was observed. These subjects had blood levels of hypericin and pseudohypericin twice those seen during normal use for the treatment of depression (22.8 and 16.2 ng/mL, respectively). It is believed that the photoactivated hypericins are responsible for this effect. No other adverse effects were seen in these same high dose studies.

In another study, two patients were given 0.25 mg/kg/i.v. and two were given 0.50 mg/kg/i.v. of synthetic hypericin as part of a phase-one AIDS trials. After 2-3 doses of the drug were administered, the latter two patients experienced facial pain and erythema after 5-10 minutes of direct exposure to sunlight. One of the patients on the lower hypericin dose was of Mediterranean descent and experienced severe hand pain and erythema after 13 weeks (Gulick eta/., 1992). These effects were mild and transient, however and disappeared within a few days of drug discontinuation (Anderson eta/., 1992).

In an open study of 3250 patients, the most commonly experienced side-effects reported were gastrointestinal symptoms (0.6%), allergic reactions (0.5%) anc~ fatigue (0.4%) (Wolk eta/., 1994). In a meta-analysis of 23 studies, 19.8% of patients using Hypericum preparations reported side effects, as compared to 35.9% of subjects using standard antidepressant medications. A total of 4% of patients in the Hypericum group dropped out in comparison with 7.7% receiving standard antidepressants (DeSmet and Nolen, 1996).

Side effects associated with the external use of Hypericum preparations have been noted in two anecdotal reports. In one case, a Hypericum gel was used to treat a sprained ankle. T his was then followed by ultrasound therapy. Soon after treatment the patient worked in direct sunlight and developed second degree burns which led to scarring. The second case was treated similarly and resulted in extensive burning that took months to heal, but left no permanent scarring (Upton, 1996).

No negative influence on general performance or the ability to drive a car or operate heavy machinery has been reponed with Hypericum use (ESCOP, 1996).

Interactions In mice Hypericum extract was reported to significantly prolong narcotic-induced sleeping rimes and antagonize the effects of reserpine (Okpanyi and Weischer, 1987). Conversely, hypericin was reported to cause a reduction in barbiturate-induced sleeping times (Oztiirk eta/., 1992). The mechanism for these interactions and the reason for these seemingly opposing findings are not known, but may be due to pharmacokinetic alterations of the

test drug. AMERICAN HERBAL PHARMACOPOEIA" '

ST . Jo HN's W oRT M o NOGRAPH

27 TOXICOLOGY Many references report that Hypericum is toxic due to the presence of the photosensitizing compound hypericin. However, toxicity in humans consuming crude Hypericum prepara­ tions is very rare and its safety, when consumed within normal therapeutic dosages, has been well established (Wolk et al., 1994).

Formal toxicology studies performed with the LI 160 preparation reported the no-effect single dose as greater than 5000 mg/kg (Leuschner, 1996). In a 26-week chronic study in rats and dogs at oral doses of 900 and 2700 mg/kg, only nonspecific symptoms of toxicity were seen, including reduced body weight, slight pathological changes in liver and kidneys due to the large metabolic load, and some histopathologic changes in the adrenals. No effects were seen on fertility or reproduction. No mutagenic potential was evident. Long-term (~2 years) carcinogenicity studies are just being completed.

In another toxicity study of rats administered Hypericum at 5% of their total diet for 119 days, no adverse effects on the liver or significant tissue lesions were found. Similarly, no effects on various hepatic drug metabolizing enzymes were observed (Garrett eta!., 1982).

In vitro mutagenic activity has been cited when the oil, extracts, and tinctures are applied to cell cultures. Quercetin has been identified as the genotoxic component (Hansel et al. , 1993; Poginsky et al., 1988). However, mutagenic research in other in vitro and in vivo models was negative, indicating no mutagenic potential for a 1:4 water-ethanolic extract yielding 0.2-0.3% hypericin and 0.35 mg/g quercetin (Hansel et al., 1993). Additionally, quercetin's potential as a mutagenic agent has also been assessed by the International Agency for the Research on Cancer. It was concluded that no valid evidence exists for carcinogenicity of quercetin in humans, since the amount of quercetin derived from the normal diet is many times higher than the amount of quercetin ingested from the therapeutic use of plants (Hansel et al., 1993).

There is a potential for auto-intoxication and overdose in both severely depressed patients and patients with HIVI AIDS. Treatment of potential overdose consists of monitoring for erythemas and protecting from sunlight for up to one week after intoxication (Hansel et al. , 1993).

Toxicology of Hypericum in Range Animals Toxicity of Hypericum in range animals is well documented. White-skinned cattle, horses and sheep exposed to strong sunlight after Hypericum consumption exhibit the most striking symptoms, but this only occurs in animals prone to consuming large amounts of fresh material. Animals with pigmented skins or those not exposed to bright sunlight are reported to remain symptom-free after eating these plants (Miinscher, 1961). It has been reported that sheep are affected after consuming 4% of their body weight of Hypericum. A cow is affected after consuming 1o/o of its body weight. Doses of up to 1-3 g/kg of Hypericum in calves demonstrate no photosensitization activity (Southwell and Campbell, 1991).

Cattle and sheep affected through experimental feedings developed a high tempera­ ture, rapid pulse and respiration, tendency to diarrhea and mild dermatitis. Although affected animals may show severe symptoms, they rarely die of Hypericum poisoning (Tehon, 1946). Purified hypericin administered to rats at 1-2 mg/rat i. p., followed by exposure to sunlight resulted in death in 1-2 hours. When mice were administered 0.25-0.5 mg of hypericin and exposed to a 2000 watt lamp for 30-minutes, the animals died within 24 hours. Control mice injected with 3-4 mg of hypericin and kept in the dark survived (Horsley, 1934).

AMERICAN In the Botanical Safety Handbook (BSH) of the American Herbal Products H ERBAL Association, Hypericum has a 2d classification with notices that it may potentiate P HARMACOPOEIATM pharmaceutical MAO inhibitors, is a photosensitizing agent, and contains high amounts of tannins (McGuffin et al., 1997, in press). As previously discussed, in vivo MAO inhibiting

ST. JoHN's W oRT activity has not been demonstrated with Hypericum and it should not potentiate the effects M oNOGRAPH of standard MAO inhibitors. Also, photosensitization does not usually occur when Hypericum is used within its recommended dosage range. 28 REGULATORY STATUS U.S.A. Regulated as a dietary supplement (PL:41 7). Approved as a natural flavoring in beverages, must be free of hypericin (Office of the Federal Registry, 1994). Australia Included as an active ingredient in products li sted in the Australian Register ofTherapeutic Goods. Canada Accepted traditional indications: sedative, nervine, diuretic, and antispasmodic in gastrointestinal disorders. Topical: promotes wound­ healing (vulnerary), shrinks and soothes hemorrhoids (IPS , 1990). Currently under review. Council of Europe Natural fl avor source. Hypericin not to exceed 0.1 mg/kg in finished Hvpericum perforatum. food product (Newall et a!. , 1996). Ph oto © 1997 Jill Stansbury. Czechoslovakia Official in Pharmacopoeia (Reynolds, 1993). ESCOP Required to contain not less than 0.04% of naphthodianthrones of the hypericin group (total hypericin), calculated as hypericin. Indications: Mild to moderate depressive states (ICD-1 0 category F32.0, F32.1); somatoformic disturbances, including symptoms such as restlessness, anxiety, and irritabili ty (ESCOP, 1996). France Approved for topical application as an emollient for urticaria, chaps, bruises, frostbite, insect bites, sunburns, and other minor burns and for pain of the oral cavity or oropharynx (Bruneton, 1995). Germany German Drug Codex: Required to contain at least 0.04% of the hypericin group calcul ated as hypericin (DAC, 1986). Indications: Psychovegetative disturbances, depressive states, fear and/ or nervous anxiety. Oil preparations: Dyspeptic conditions. Approved external uses: For the treatment and follow-up treatment of piercing and contused injuries, myalgia, first degree burns (DAC, 1986). Commission E: Psychological disturbances, depression, anxiety, nervous unrest; oil for bruises due to trauma, myalgi, and first degree burns (Blumenthal eta!. , 1997). Poland Official in Pharmacopoeia (Hobbs, 1989). Romania Official in Pharmacopoeia (Reynolds, 1993). Russia Official in Pharmacopoeia (Reynolds, 1993). Switzerland Required to co ntain a minimum of 0.08% total hypericin computed as hypericin (Pharm acopoeia Helvetica, 1996). United Kingdom Legal Category (Licensed Products): GSL (for external use only) (Gt 4l (Newall et a!. , 1996). Occurs in British Herbal Pharmacopoeia. Actions: Sedative, astringe nt. Topically: Analgesic, antiseptic. Indications: Menopausal neurosis, excitability, neuralgia, fibrositis, sciatica (Bradley, 1983). Topically: Wounds.

REFERENCES Adamski , R., Styp-Rekowska, E. Stability of hypericin in jui ce, dry extrac t and tablets fro m Hypericum per[oratwn plants. Farm. Pol. 197 1; 27: 237-241. Ai zenm an, B.E. Antibioti c preparations from Hypericum perforatum. Microbial. Zh. 1969: 3 1:128- 133. Akhtardzhiev, K., Kitanov, G. Catechi n composition of Hypericum perforarum. Farmarsiva (Sophia). 1974: 24: 17-20. Akhtardzhi ev, K., Koleva, M., Kit anov, G., Ninov, S. Pharmacognosti c study of representati ve of Arum. Althaea and Hypericum species. Farmarsiya (Sophia). 1984; 34:1-6. Alyukina, L.S. Dynami cs of the accumulation of fla vonoids in Hypericum perforatum and Hvpericum scabum. Tr. In st. Bot. Akad. Nauk. Kaz. SSR. 197 1: 29: 110- 127. Anderson. R. , Fl ynn, N., Jain, S., Samuels, S., Perkins. C., Enders. S. Testing is not enough: do ID U know their serostatus' Abstract from the Proc. VIII. International Conference on AIDS. Amsterdam; 1992. Araya, O.S., Ford, E.J .H. An in vestigation of the type of photosensiti zati on caused by the ingesti on of St. John's won (Hvpericum perforatum) by calves. Journal of Comparative Pathology. 198 1: 135- 14 1. Bailey, L.H . Manual of Cultivated Plants. Ne w York: Macmillan Pu blishing Co .. Inc.; 1949. Beni gni, R .. Capra, C. , Cattorini, P.E. Hypericum . Pi ante Medicinali : Chimica. Farmacologia e Terapi a. Mil ano: ln vemi & Della Beffa: 197 1. Bennett, G.J., Lee, H.H. Xanthones fro m Gulliferae. Phytochemistry . 1989; 28:967-998. Berghofer, R., Htilzl, J., (Kl ein , S. Trans. cou11esy of Nature's Way). Johanni skraut (Hypericum perforarum L. ): Prii fung auf AMERICAN verfalschung. Dew sche Aporheker Zeirung. 1986; 126. H ERBAL Berghtifer, R., Htilzl, J. Biflavonoids in Hypericum perforatum. Part I. Isolation of 13 , 11 8- biapi genin . Planra Medica. 1987: 216-2 17. P HARMACOPOEIA"' Berghtifer, R. , Htilzl, J. Isolation of 13', 11 8- biapi genin (ament ofl avone) from Hypericum perforatum. 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Benefi ts and risks of the Hypericum extract Lll60: drug monitoring study with 3250 patients. J. Geriatric Psychiatry Neurology. 1994; 7:S34-38. Yip. L., Hudson, J.B., Kowalik, E.G. , Zalkow, L.H ., Towers, G.H.N. Antiviral activity of a deri vative of the photosensiti ve compound hypericin . Phytomedicine. 1996; 3: 185 -190. Zhebeleva, T.l. Effect of ecological conditions on the morphology and flavonoid accumul ati on of Hypericum perforatum. Rast. Resu r. 1973; 9:402-404.

AMERICAN H ERBAL PHARMACOPOEti'"

ST. J o HN's W oRT M oNOGRAPH 32 In 1994, Roy Upton, President of the American Herbalists Guild in Soquel, California, initiated the American Herbal Pharma­ Table S: American Herbal Pharmacopoeia rM Monographs copoeia (AHP). With a scant level of funding to date, Upton has been successful in preparing three extensive monographs: Astraga­ AHP Monographs Completed lus, reishi mushroom (Ganoderma), and willow (Salix spp.). Addi­ Hawthorn Crataegus laevigata tional monographs are currently being prepared, edited, and peer St. John's Wort Hypericum perforatum reviewed, including the St. John's Wort (Hypericum petforatum) just Valerian Valeriano officina/is completed and published in this issue of HerbalGram. Willow bark Salix spp. Upton has assembled an international review panel of herbal­ ists, scientists, and natural health practitioners to peer review each AHP Monographs near completion monograph. The AHP monographs are combined monographs; they Ashwagandha W ithania somnifera include much of the standard definitional and analytical informa­ Astragalus root Astragalus membranaceus tion found in conventional pharmacopeia! monographs on standards, Garlic Allium sativum Reishi mushroom Ganoderma fuc idum plus therapeutic and clinical information. However, AHP goes a Schizandra Schisandra chinensis step further with the inclusion of the Chinese and Ayurvedic ener­ getic information not found in standard Western pharmacopeias and AHP Monographs in Process clinical literature on herbs. Billberry Vaccinium myrtillis It is still uncertain how AHP will publish its monographs. Black Haw Viburnum prunifolium Publication of individual monographs or bundling them into a series Chamomile Matricaria chamomilla of books is being contemplated. More information on AHP is avail­ Chaste berry Vitex agnus castus able from American Herbal Pharmacopoeia, 3411 Cunnison Ln., Cramp bark Viburn um opufus Soquel, CA 95073. Phone/fax: 408-464-2441. Dandelion Lf & Rt Taraxacum officina/is Dong Qui Angelica sinensis BRITISH HERBAL PHARMACOPOEIA Echinacea Echinacea angustifo lia, The British have always enjoyed an advanced herbal awareness. E. pal/ida, E. purpurea Herbalism has been accepted or at least tolerated in English society Ginger Zingiber officinale since King Henry VIII signed the Herbalists' Charter in the 1540s Ginkgo Ginkgo biloba granting by royal decree the right for herbalists to practice their art. Ginseng Panax ginseng, P quinquefolius In 1983 the British Herbal Medicine Association (BHMA) published Goldenseal Hydrastis canadensis the British Herbal Pharmacopoeia, revised in 1990 as Volume I Lemon balm Melissa officina/is Glycyrrhiza uralensis, G. glabra which contains analytical standards for 84 herbs popular in England. Licorice Milk thistle Silybum marianum In 1992 BHMA published a companion British Herbal Compen­ Momordica Momordica charantia dium, Volume I, which gives therapeutic monographs on the same Nettles Lf & Rt Urtica dioica 84 herbs. The BHP was revised and expanded in 1996 and now Peppermint Mentha piperita contains monographs on 169 medicinal plants. Both publications Saw palmetto Serenoa repens are available in the U.S. from the ABC catalog. Uva ursi Arctostaphylos uva-ursi

FDA HERB MONOGRAPHS? For a brief period it appeared as if even FDA was attempting to get into the herbal monograph act. A letter sent out in November 1995 to various herb scientific and trade groups requested assistance in identifying the most widely used herbs in U.S. commerce. The let­ ter indicated that FDA was developing monographs "to aid in the identification of botanical dietary supplements." FDA reportedly intended to describe 20-25 botanicals "of current importance in com­ merce." (Gecan, 1995). However, since that time there appears to be no interest at the agency to pursue this course of action and the project appears to have taken a different turn. A botanist/microbi­ ologist at FDA has assembled macroscopic and microscopic infor­ mation on 17 plants popular in the herb market, has obtained vouchered samples of each herb, and has produced photo-micro­ graphs of their cellular structures. These have been put onto a CD­ ROM for the purposes of asssisting FDA field officers in determin­ ing proper botanical identity of materials in field inspections (Betz, 1997). The CD-ROM will be made available to the public at some undetermined time.

The first edition of the U.S. Pharmacopoeia, 1820. Courtesy of the Lloyd Library and Museum, Cincinnati, OH.

HERBALGRAM No. 40 • 37 CONCLUSION Table 6: Partial Outline of WHO Medicinal Plant The availability of various types of herbal monographs will help fill Monographs the current need for information on quality control and safe, respon­ developed by Prof. Norman R. Farnsworth, Harry H.S. Fong, sible usage of herbal products. As the industry continues to grow at and Gail Mahady, PCRPS, University of 11/inois, Chicago record levels, the industry's use of the information in herbal mono­ graphs will ultimately help health consumers by making available TITLE (Latin) herbal products of increased quality and reliability. 0

Definition REFERENCES Synonyms Betz, J.M. 1997. Personal communication, Apr 7. Vernacular names Blumenthal, M., J. Gruenwald, T. Hall, C. W. Riggins, R. Rister (eds.). S.Kiein and R. Rister (trans.). 1997. German Commission E Monographs: Therapeutic Monographs on Me­ Plant description dicinal Plants for Human Use. Austin, Texas: American Botanical Council (i n press). Description of plant material Blumenthal, M. 199 1. European Scientific Cooperative for Phytotherapy Conference: General appearance European Harmony in Phytotherapy. HerbalGram 24:41-43. Boyle, W. 199 1. Official Herbs: Botanical Substances in U.S. Pharmacopeia, 1820- 1990. Organoleptic properties East Palestine, OH: Buckeye Naturopathic Press. Microscopic characteristics Farnsworth, N.R. 1996. Personal communication, Jan. 5. Powdered drug Gecan, J.S. 1995. letter to Mark Blumenthal, Nov. 2. Grady, L.T. 1995a. Botanicals of Interest to USP: 1820 - Present. Rockville, MD. The U.S. Geographical distribution Pharmacopeia. General identity tests Grady, L.T. 1995b. Personal commun ication, Sept. 25. Keller, K. 1996. Herbal Medicinal Products in German and Europe: Experiences with Purity tests National and European Assessment. Drug Information Journal 30: 933-948. Microbiological Lloyd, J.U. 1929. Origin and History ofall the Pharmacopoeial Vegetable Drugs. Cincinnati, External use OH: Caxton Press. Mahady, G.B. 1997. Personal communication, May 6. Internal use Mahady, G.B. 1996. Personal communication, Dec. 17. Chemical Mills, S. Y. 1997. Personal communication, May 21. Foreign organic matter Reynolds, B. 1997. Personal communication, Mar. 23. Reynolds, B. 1996. Personal communication, Aug. 8. Total ash Ringel, K.P. 1997. Personal communication, May 7. Acid-insoluble ash World Health Organization. 1991. Guidelines for the Assessment of Herbal Medicines. Geneva: WHO. Reprinted as Classic Botanical Reprint #234. American Botanical Council, Alcohol-soluble extractive Austin, TX. Pesticide residues Zhang, X. 1994. Letter to H. Cranz of AESOP, Nov. 22. Radioactivity residues Assays Chemical assay Biological assay Major chemical consituents Dosage forms Storage Clinical use Pharmacology Experimental pharmacology Clinical pharmacology Contraindications Pharmacopcea Warnings Londinen!is, Precautions General Drug interactions A~TIQYAETNOV A vfiunflima , fcduiO colleCl:a, Drug/laboratory test interactions ;accunti{I;me cxa.mtl\lt'3, qu~> tidl ou.~upuif.,~ coofir.mta Carcinogenesis, mutagenesis, impairment of fertility 'tkubumur. Pregnancy: teratogenic effects Opua Medicorum Col!C:gij LoH D IH& ~su. Pregnancy: non-teratogenic effects Nursing mothers Pediatric use Side effects Posology (dosage) Addittional comments References

Pharmacopoea Londinensis, 1618 (facsimile of original). Courtesy of the Lloyd Library and Museum, Cincinnati, OH .

38 • HERBALGRAM No. 40 linn arden

by Hakan Tunon, Ph.D. , Uppsala University, Uppsala, Sweden

The orangery in Linnaeus' garden. In the winter he stored plants, such as bananas, that couldn't survive in the Swedish climate. Photo by the author.

Restored in 1920 from its state of neglect and with at the universities of Leiden and Utrecht. Rudbeck wanted renovations currently continuing, Linnaeus' garden to create something similar in Uppsala. He brought bulbs is a green oasis in central Uppsala, Sweden. and seeds of rare plants from Holland. He introduced The history of this garden begins a half-century before the plants such as tulips, hyacinths, and the Peruvian night­ birth of Linnaeus in 1707. 1t was founded in 1655 by Olof shade-today called the common potato-to Sweden. [Olaus} Rudbeck the older, appointed professor of The garden was soon bought by the University of Uppsala. medicine and botany at Uppsala University in 1658. He The plant catalog, published in 1658, mentioned had just returnedfrom a journey to Holland, England, and approximately 1,000 different species; by 1685 the France where he was impressed by the botanical gardens publication included more than 1,800 different plants.

HERB ALGRAM No. 40 • 39 Sponsaliorum Plantarum (A Prelude to the Marriage of Plants), in which he introduced the idea that the pistil and the stamina were sexual organs of pl ants. Thi s publication was soon spread among the medical students and a copy came under the eye of Rudbeck.

LINNAEUS AS DEMONSTRATOR The medi cal professor was impressed by the new ideas and arranged a meeting with Linnaeus at Cel sius' home. Later that year, Rudbeck reti red, naming Linneaus as his substitute. The medical faculty sub­ sequentl y appointed Linnaeus demonstrator botanici at the botani ­ After his journey to cal garden, where he taught botany to the medi cal students. Linneaus Lapland, pioneer gave lectu res in botany and led excurs ions into th e botanical garden, ethnobotanist Carl the area he had been given the responsibility of supervising. Hi s Linnaeus sometimes wore Lappish lectures were well attended since not onl y the medical students fo und garments to his seminars fascinating but also students and teachers from other demonstrate the disc iplines. He taught botany in an enthusiastic way th at captured w ays of the Saami his audience. In the summer of 173 1, in addition to hi s career as people for hi s botanical teacher, he attended lectures in medicine and examined students in Uppsala the flowers in the botanical garden. Hi s thorough investi gati ons of University. [Plants, plant morphology showed him a useful system for botani cal classi­ People, and fi cati on- the sexual system-and he started to rearrange the plants Culture-The Science according to hi s own new system. of Ethnobotany by Michael J. Bolick and Paul Alan Cox, see REVIVAL OF THE GARDEN excerpt on page 54.] As a result of an academic controversy Linnaeus left Uppsala in Courtesy and December 173 1 and spent the fo ll owing years journeying within copyright of Museum Sweden and abroad. During hi s travels through Lappland in north­ of Natural History, ern Sweden, in additi on to taking notes on the fl ora of the area, Leiden , Holland. Linnaeus made observati ons on the Lapps themsel ves. He took care­ ful notes on the manner in which they li ved and their medicinal and economic uses of many plant species. In 1735, realizing that in order to have a successful career he must obtain a medical degree, he travelled to Harderwijk, Holl and, and, within a week, passed his exams, obtained permission to print hi s dissertation which he had THE GREAT FIRE DEVASTATED THE GARDEN written earlier in Sweden, defended his di ssertation, and received Rudbeck was succeeded as professor in medi cine and botany by his his diploma, beco ming a doctor of med icine. He also published son, Olof Rudbeck the younger, in 1692, but continued to be a dri v­ several books, e.g. , Systema naturae (System of Nature, 173 5), ing fo rce at the botani cal garden. In 1702 a great fire devastated Fundamenta botanica (Fundamentals of Botany, 173 6), Genera three-fo urths of the city of Uppsala. The castl e, the cathedral, and plantarum (Genera of Plants, 1737) and Hortus Cliffortianus (The the botanical garden were partl y ruined. The loss of his beloved Clifford Garden, 1737). Linnaeus returned to Sweden in 1738 and garden devastated Olof Rudbeck the older and he died in the au­ worked as a ph ys ician in Stockholm . In 1741 he was appointed tumn th e same year. His son was also di scouraged. This, in combi­ professor in Uppsala and in the spring of 1742 his dream came true nati on with the fin ancial situati on in Sweden and Uppsala, made it when he was made head of the botani cal garden. The first thing he hard to restore the garden to its old splendor. Both Uppsala city and did was to prepare for a total reconstructi on of the garden. He man­ the uni versity had suffered considerable losses in the fire and Swe­ aged to employ the German gardener Nietzel, who had worked at den was a country involved in endless and costl y wars. Cliffo rd 's Hartecamp, close to Haarlem in Holland . The royal ar­ chitect Carl Harleman developed a renovation plan fo r the garden, A PRELUDE TO A GREAT BOTANIST the orangery (glass-wa ll ed enclosure for growing oranges in cool In September 1728 a young student named Carl [Carolus] Linnaeus climates) , and the greenhouses. These plans were soon completed left the uni versity of Lund to continue his studies in Uppsala since and Linnaeus wrote to all hi s fri ends abroad, who responded by send­ the botani cal section ofthe medi cal education were considered to be ing seeds and bulbs. In 1748, he published hi s Hortus Upsaliensis­ better there. He had great expectati ons of the botani cal garden in hi s hi story of the botanical garden and its future. In 1748 the num­ Uppsala, but they were not fulfill ed. He wrote in a letter that the ber of species had grown to approximately 3,000. In the orangery garden onl y contained a coupl e of hundred spec ies, none of them he grew coffee, cocoa, ri ce, ginger, different kinds of cacti , and many rare. No lectures in botany were given since Rudbeck the younger other plants. He also kept a tea bu sh and a banana plant. By now spent most of his time on a phil ological project. So, Linnaeus spent Linnaeus was content and hi s happiest moments were those spent in much time wandering in what was left of the botani cal garden, ex­ the garden. amining plants. On one of hi s visits he became acquainted with the theology professor Olof Celsius-a noted amateur botanist. They THE HEADQUARTERS became fri ends and Linnaeus soon became one of Celsius' proteges. The garden consisted of five areas or quarters each of which served Linnae us dedi cated to Celsiu s a small publi cation, Praeludia a particul ar purpose. Today, only four quarters are culti vated. The

40 • HER BALGRAM No. 40 field to the ri ght (when facing the orangery) is area annua-the an nual quarter-where ann ual and biannual pl an ts are grown, and to the left there is area perennis, with perennial plants. Both of these quarters are organised accord ing to Linnaeus's sexual system, i.e., the plants are pl anted in the ord er of hi s classes depending on the number of stamina (i. e., Monandri a, Di andria, Triandria, etc. , ending with the 24th and last class Cryptogamia, that lacks stamina and pi stil s). The garden is surrounded by a large number of species of Swedi sh trees and shrubs. In front of the orangery there is a triangle-shaped quarter where Linnaeus planted specimens that spent th e winter in th e orangery. That area is used today for an open- air cafeteria in the su mmer. The area to the left of th e cafeteri a is used fo r plants that flower in the spri ng and to the right for autumn fl ow­ ers. Linnaeus also arranged three ponds, illustrating three different ecological systems, marsh, creek, and pond. These were formerly used for irrigation of the garden. The quarters were originall y sur­ rounded by different kinds of bushes, to show various examples of 'live fences' th at could be used in Sweden. Today these areas are surrounded by hedges of fir (Picea abies).

THE RISE AND FALL ..• During the following years Linnaeus stayed in Uppsala as much as possible si nce he could not bear to leave his garden. The garden not on ly contained pl ants but also animals, e.g., racoons, ew and Old World monkeys, pigeons, and parrots. Linnaeus worked in hi s gar­ den , taught botany, and wrote books. He published Flora Svecia (Flora ofSweden) in 1745, Fauna Svecia (Fauna ofSweden) in 1746, Hortus Upsaliensis (The Garden of Uppsala) in 1748, Materia medica in 1749, Philosophica botanica (Botanical Philosophy) in Publications by 1749, and Species plantarum (Species of Plants) in 1753. In Spe­ Linnaeus . Top : Materia cies plantarum he first introduced the binomial nomenclature of Medica, 1749. plants. In 1758 the same system was applied to th e animals in the Center: Sys tema lOth edition of hi s Systema naturae. Linnaeus continued working naturae, 1740 , eagerly in hi s garden until 1774 when he had his first stroke. In German version. 1776 he had another one, more severe. Hi s movements became un­ Bottom : Sponsalia Plantarum, 1746 . All steady and his talk and thoughts started to become unclear. photos courtesy of the He died on January 10, 1778, in the professor's house in the Lloyd Library and botani cal garden-the same hou se in which Ol of Rudbeck the older Museum, died-today a museum . Linnaeus's son, Carl von Linne the younger, Cincinnati, OH. continued as professor and keeper of the botanical garden, but th e university admini stration showed no interest in the garden and it started to decline. Linnaeus the younger managed to stave off th e garden's total decay. He died in 1783 and that was the end of th e botanical garden at thi s site.

THE GARDEN MOVES The location close to the river Fyris had always been a great prob­ lem , since the river flooded the garden each year and caused dam­ age. Carl Peter Thunberg, Linnaeus the yo unger's successor as pro­ fessor in medi cine and botany, managed to get funds to move the botanical garden to a site close to the castle in Uppsala- its present location . The garden by the river soon came to be used by the neigh­ ti sts from foreign countries were the quarters, covered with grass boring people as a kitchen garden. The orangery was rebuilt in 181 8 and surrounded with hedges. Ten years later, the Swedish Linnean and used for a student association. The professor's house built by Society was fo unded with th e aim of restoring Linnaeus's botanical Rudbeck th e older and rebuilt by Linnaeus was used by the depart­ garden, co ll ecting items th at had belonged to him, and publi sh ing ment of music and contained an apartment for th e music director of papers about him and his students. In 1918 the uni versity donated the university. th e area as well as the houses-the orangery and the professor's house-to the soc iety. The garden was reconstructed and by 1920 BICENTENNIAL OF LINNAEUS'S BIRTH was opened to the public. The professor's house was not added to When the two hundredth anni versary of Linnaeus's birth was cel­ the coll ec ti ons until 1935 when the music director mo ved to another ebrated in 1907, all that the university could show the visiting sc ien- apartment.

HERBALGRAM No. 40 • 41 His special porcelain from China decorated with his favorite fl ower, Linnaea borealis L., Caprifo li aceae, is exhibited. Also in pl ace is hi s medical shrine containing the materi a medica used fo r demonstrati on in the seminars for the medical students. It still con­ tains crude drugs and extracts of medicinal pl ants that were in medi­ cal use during the 18th century. Some of the extracts are from plants that were impossible to grow in the northern climate of Uppsala, e.g., several preparations of cinchona bark (Cinchona sp., Rubiaceae), jalap root (Ipomoea purga Haynes, Convolvul aceae), senna leaves (Cassia sp., Fabaceae) as well as inorgani c salts and exoti c drugs li ke the Goa stone. Visitors can see the ori ginal microscope and magni fy ing glasses that Linnaeus used when studying the pl ants' sexual parts when developing hi s classificati on system.

THE FUTURE OF THE GARDEN Linnaeus's summer cottage, Hammarby. He took walks The garden has been cultivated since 19 18 and is continuously evolv­ from Uppsala to Hammarby with his students while ing to more closely approximate Linnaeus's original garden. In Au­ demonstrating the local flora and fauna . gust 1995 four new cast iron urns were pl aced on the roof of the orangery. The ori ginal urns have been gone since Linnaeus's days, but th ere were still two of the ori ginal ones at the main gate whi ch were used to make replicas. After these ori ginals were stolen in Au­ gust 1995 but then anonymously returned one month later, they were replaced with replicas. LINNAEUS'S MUSEUM Dr. Lars Jonsson, the head gardener, dreams of total restora­ Today there is a museum in the former professor's house. The Swed­ ti on. There are also two further sites connected to Linnaeus in ish Linnean Society has renovated Linnaeus's home and converted Uppsala - hi s two summer cottages, Hammarby and Savja. Both it to a museum that contains many items of interest. One can see a are kept as museums dedi cated to the great botani st of Uppsala. reproducti on of Martin Hoffman's painting with Linnaeus in a Saami Today visitors can view the I ,300 different pl ants that were (Lapplanders) costume. The magic drum shown in th at painting is hi s "library." During the summer season (until September 30) the also exhibited. garden is open daily from 9 a. m. to 6 p.m. 0

BoTANICAL NAMES

As part of our new For example, the scientific name for narrow-leaved purple cone­ policy in HerbaiGram, flower is Echinacea angustifo/ia DC, (Asteraceae). Echinacea is the the scientific names of genus name, and angustifalia is the species designation. DC is the plants and the families standard abbreviation for the name of Augustin Pyramis de Cando lie, to which they belong the 19th century Swiss botanist who first applied the name. Asteraceae will be provided. The is the scientific name for the aster or thistle family, also referred to as assignment of scien- the composite family, Compositae. tific names, which are In the case of purple coneflower, Echinacea purpurea (L.) Moench, the same worldwide, is governed by the International Code of Botanical there are two authors recognized. The '(L.)' indicates that Carl Nomenclature (ICBN), a formal listing of the rules developed by the Linnaeus, the 18th century Swedish botanist who was the first to International Botanical Congresses. consistently use the binomial system of nomenclature, first described Complete species names consist of a Latin binomial, which is the species, giving it the specific epithet purpurea. He originally placed always written in italics, and the standard form of the name of the the species in the genus Rudbeckia. Moench later transferred the person who was the author of the plant name. The Latin binomial species to the genus Echinacea. consists of the name of the genus, the first letter of which is always Presented here is but a small part of the precise system for the capitalized, and the specific epithet, which is written in lowercase {i.e., naming of plants. Please consult the ICBN {the most recent edition species = genus + specific ephithet). is dated 1994,W. Grueter, Chairman) if you are interested in learning more about the rules of nomenclature. Cultivated plants are cov­ ered by the International Code of Nomenclature for Cultivated Plants Publications above, by Linnaeus: two versions of (ICNCP) dated 1995, Piers Trehane, Editor. ABC Advisory Board Fundamenta Botanica, 1736 and 1741 . Courtesy of the member Arthur Tucker co-authored Appendix No. XI on cultivar Lloyd Library and Museum, Cincinnati, OH. checklists.- Phyllis Boyd

42 • HERBAL GRAM No. 40 CONFERENCE REPORT

Testing Botanicals AReport on Developing the Scientific and Clinical Evidence to Support the Clinical Use of Heterogeneous Botanical Products Washington, D.C., Jan. 27-28, 1997 by Mark Blumenthal

The growth and maturation of the botanical Freddie Ann Hoffman, M.D., Deputy a desired element of an herb company's wish­ industry is made evident by many factors, Director of the Medicine Staff at the FDA's ful thinking, she said. "It is becoming re­ one of them being the Third Conference on Office of Health Affairs, noted in her intro­ quired." Botanicals sponsored by the Drug Informa­ ductory remarks that the conference would Dr. Leaders made a brief presentation tion Association (DIA) held in January 27- concentrate on what is necessary to define a for Melville K. Eaves of the W. Schwabe 28, 1997, in Washington, D.C. DIA is an product scientifically to assure its activity Company of Karlsruhe, Germany, who was international organization offering a neutral from a therapeutic perspective. unable to attend, on "The Pros and Cons of forum for ideas in areas of drug research, Peggy Brevoort, CEO of East Earth Heterogeneous Botanical Products." Accord­ marketing, and regulation. DIA has held two Herbs and past president of the American ing to Eaves, reflecting the view of many of previous conferences on botanicals in the Herbal Products Association (AHPA), pre­ his European coll eagues, pharmacological past two years, both co-sponsored by the U.S. sented "Overview of th e U.S. Botanical activity of a botanical can be enhanced by Food and Drug Administration (FDA) and Market," presenting facts, figures, lists of chemical standardization, thereby increasing the Office of Alternative Medicine (now re­ leading herbs and related information to the the level of active ingredients and reducing named the Office of Complementary and growth of herbs in the U.S. The U. S. herb some of the potentiall y unsafe compounds. Alternative Medicine) at the National Insti­ market is about 30 years old. Five or more He made an interesting point on herbal tutes of Health (NIH). This third conference years ago the industry had not yet matured safety. If the products are assumed to be was also sponsored by the Office of Dietary enough to consider scientific considerations toxic, and they are on the market in most of Supplements (ODS) at NIH, a new agency discussed at conferences like this, although the world as many critics would have us be­ created by the Dietary Supplement Health and some companies, especially European firms, lieve, where is the toxicity? The dose/re­ Education Act of 1994 (OSHEA) which is were obviously up to speed from a quality sponse curve appears to be very shallow. If coordinating and stimulating research in di­ control and scientific point of view. She also people have problems with herbs, they usu­ etary supplements. discussed the lack of accurate statistics to ally discontinue their use before the onset of The title of this conference was "Bo­ measure the U.S. botanical market. [For serious adverse reactions. tanical Testing: Developing the Scientific and more information on this, see her article in Ten years ago it may have been diffi­ Clinical Evidence to Support the Clinical Use Herba!Gram 36.] cult to get a well-known clinical researcher of Heterogeneous Botanical Products." The Ms. Brevoort estimated the size of the to test herb products. Today, according to term "heterogeneous" is key; botanical prod­ U.S. herb market. She uses the figure of ap­ Eaves, there is progress and the ability to get ucts by their very nature are composed of proximately $2 billion for 1996 but acknowl­ clinical data has increased. He noted a sur­ numerous naturally occurring chemical com­ edges that the actual number may be even vey that healthcare professionals under age pounds, compared to conventional pharma­ higher. She noted that the fastest growth for 40 are more open to prescribing herb prod­ ceutical medicines that usuall y consist of one herbs is occurring in the mass market where ucts than those from 40-70. Also, in some isolated, purified chemical which is "homo­ herbs sold about $200 million in 1996, 10 per­ cases older M.D.s may be willing due to pos­ geneous." Thus, in their chemical diversity cent of the estimated total market. sible fami liarity with the former use of herbs and variability-their heterogeneity-bo­ She commented on the new good as medicines. tanical products present a set of challenges manufacturing practices (GMPs) mandated Edward M. Croom, Ph .D. , Coordina­ not encountered with single molecul ar en­ by DSHEA, published as proposed regula­ tor, Phytomedicine Project, School of Phar­ tity pharmaceutical drugs. tions by FDA a few weeks later. She noted macy, Uni versity of Mi ssiss ippi , gave an The conference was designed and that the use of hi gh performance liquid chro­ overview of the previous DIA conference on chaired by Floyd E. Leaders, Ph.D., a phar­ matography (HPLC) or similar analytical botanicals, "Botanical Quality: Identification macologist who has been instrumental in procedures to determine batch-to-batch con­ and Characterization." He discussed the vari­ planning the previous two DIA conferences sistency of botanical products is now becom­ ability of pl ant constituents based on on botanicals and who has become active in ing the norm at many herb companies as they chemotypes, harvesting methods, storage, the area of assisting pharmaceutical and become more sophisticated on a quality con­ and extraction techniques. He suggested that herbal companies in developing methods of trol and quality assurance level. The devel­ manufacturers need to keep botanical refer­ obtaining drug approval for botanical prod­ opment of an in-house laboratory is no longer ence standards for their herbal materials to ucts. HERBALGRAM No. 40 • 43 CONFERENCE REPORT

determine proper identity, quality (i.e., iden­ caused some problems. "For example," he must be compared and tested directly to syn­ tity, purity, strength). They also need to have says, "does an extract of echinacea prepared thetic drugs. He also strongly suggested that Jiving reference collections in addition to with 40 percent ethanol have the same con­ companies should set aside 15 percent of dried herbarium specimens. Croom's basic stituents (both quantitatively and qualita­ gross sales revenues to research in areas of point: "It is important to keep products re­ tively) as an extract made with 60 percent phytoequivalence. This is standard for Eu­ producible and of hi gh quality; let us use alcohol? The polarity of the solvent for ropean companies. Although this may seem science but use what is appropriate to docu­ echinacea has an obvious effect on the com­ expensive for U.S. companies, it is impor­ ment quality, safety and efficacy." pounds extracted and thus the therapeutic tant, because the best-selling herbs in the U.S. activity. Specifically, the high-molecular­ are those that have been most researched PHYTOEQUIVALENCE ISSUES weight polysaccharides are water soluble; the (usually in Europe). According to Tyler the One of the high points of the conference was alkamide fraction (isobutylamides) is etha­ future of herbs in the U.S. requires that manu­ the lecture from Varro E. Tyler, Ph.D., Dean nol soluble; and the caffeic acid derivatives facturers become familiar with concepts of and Distinguished Professor Emeritus, (cichoric acid, echinacoside) are both water standardization and phytoequivalence. School of Pharmacy, Purdue University, who and ethanol soluble." There were several presentations by spoke on "The Role of Botany, Chemistry Chamomile is another example. Cha­ scientists associated with European and and Pharmacognosy in the Selection Process momile tea has different contents than an American herb and phytomedicine manufac­ for Heterogeneous Botanicals." According alcohol extract. The antiinflammatory and turers. Werner Busse, Ph.D., Head, Regula­ to Prof. Tyler, phytoequivalence is the solu­ antispasmodic activity is attributed to three tory and Scientific Affairs, Schwabe Phar­ tion for the situation of multiple botanical groups of constituents: volatile oils maceuticals in Karlsruhe, Germany, gave a formulations because each product may have (bisabolol, chamazulene, matricin) are wa­ lecture titled "How Can Learned (and Un­ variations in active constituents. Phyto­ ter soluble; tlavonoids (apigenin) are also learned) from Non-U.S. Markets Be Applied equivalence is the term being used to deal water soluble; coumarins (herniarin, to the U.S. Market?'' He noted that recent with bioequivalence of a phytomedicine umbelliferone) have intermediate solubility. research in Europe with standardized extracts compared to another product that may be the So the method of preparation of chamomile (e.g., ginkgo, hawthorn, St. John's Wort) has subject of extensive research. extracts is very important. The following shown that modem phytomedicines are safe Tyler noted that the history of variables apply: percentage of alcohol in a and effective (for indications like senile de­ phytoequivalence in Germany was marked hydroalcoholic menstruum, degree of extract mentia, heart failure, or mild to moderate by previous versions of the German Phar­ concentration, uniformity of plant material, depression) and they are thus alternatives to macopeia (DAB) which specified exact con­ time and temperature of extraction. sy nthetic pharmaceutical drugs. He sug­ ditions for plant preparations, including ex­ The situation is even more complex for gested that "Phytomedicines represent part traction methods, time, and specific solvents. botanicals, such as valerian, with unknown of conventional medicine and as such deserve However, the new DAB only specifies "ap­ active constituents. Usually, the procedure the acceptance as drugs" under appropriate propriate" methods and solvents. This has to determine the activity of a plant prepara­ regulatory conditions. He noted that many tion or one of its fractions is to run a labora­ European nations (e.g., Germany, France, tory bioassay, a test on a particular animal. Switzerland) and other countries (Mexico However, Tyler said that it is not feasible to and Brazil) have specific national regulatory Eventually, run bioassays on each botanical preparation; mechanisms to deal with herbal medicines. but often the degree of activity can be deter­ Busse also spent some time explaining some mined indirectly by chemical analysis (e.g., of the basis for the German Commission E said Tyler, GC-MS, HPLC, TLC) to determine the system of approving herbs as nonprescrip­ chemical fingerprint of the botanical. Then tion medicines. One of the primary tenets of phytomeditines one needs to ask whether there are any clini­ Commission E and of European drug laws cally tested reference preparations from the in general is that the vegetable (i.e., herbal) same botanical? This means that if a lead­ drug or its preparation in its entirety is re­ must be ing botanical (e.g., ginkgo or ginseng) has garded as the active ingredient. Thus, there been shown to have particular efficacy in are no requirements to show activity of spe­ tompared and clinical trials and has been chemically ana­ cific plant chemicals in the herb, i.e., active lyzed and standardized to particular compo­ ingredients. The herb is the active ingredient. nents, then presumably another botanical Picking up on Busse's theme, Joerg tested directly extract that meets the same chemical criteria Gruenwald, Ph.D., ofPhytoMed Consulting would be phytoequivalent to the tested botan­ and the Institute for Phytopharmaceuticals ical. This is based on the presumption that in Berlin, spoke on "What are the Implica­ to synthetic the chemical compounds are qualitatively tions of Considering a Botanical Product as and quantitatively equal. a Single Therapeutic Entity?" He presented drugs. Eventually, said Tyler, phytomedicines a possible long-term system of registration

44 • HERBALGRAM No. 40 ~The Rosenthal Center for Complementary 8 Alternative Medicine~ BoTANICAL MEDICINE CouRSE

Botanical Medicine in COLUMBIA UNIVERSITY Modern Clinical Practice College of Physicians & Surgeons Oct.13 -Oct. 17, 1997 New York City, New York Limited Enrollment: REGISTER EARLY and The University of Arizona (j~·~~­ College of Medicine and College of Pharmacy Continuing Medical Education Tucson, Arizona 5 Day Course (Mon-Fri)

Name: ______You can call (212) 781-5990, At the conclusion of the course, Address: ______Fax (212) 781-6047, or email participants should have: your registration information - - ~ to the CME office if payment • developed a better understand­ ~ ing of the scientific evidence 0 Phone: ______is by credit card, (be sure to on the effects of selected u.. Fax: ______include your credit card num­ botanical remedies; z ber), or return this form to: Payment can be made by check, made out to • enhance their ability to recog­ 0 Continuing Medical nize the principal benefits and COLUMBIA UNIVERSITY, or by credit card Education Ofc. risks of botanical medicine (VISA or MASTERCARD) Columbia University therapies and the interaction ~ Tuition: $1200 for physicians College of P&S Unit 39 effects with other medications; I;; $900 other health professionals, residents, 630 West 168th Street • learned methods enabling them \j- and fellows (numbers limited) New York, NY 10032 LIJ to incorporate the use of ~ Credit Card #.______selected Western botanical remedies into their practice; Signature ______Exp. date: ___ • gained familiarity with or register online: http://cpmcnet.columbia.edu/dept/cme/con0031 .html information of the legal • History of herbs in medicine and pharmacy ! considerations in the use of • Herbs in clinical practice. botanical products; and ~ • Medical conditions including problems for the digestive, respiratory, • the ability to provide valuable information to their patients - cerebrovascular and genitourinary systems, insomnia, allergy, and more. on the effective use of Q. • Womens health issues. botanical medicine. ~ • Food as medicine; herb-drug interactions • Safety, toxicity, herb quality • Legal and professional considerations. MICHAEL BALICK, Ph.D., Director and Philecology Curator, Institute of Economic Botany, New York Botanical Carden MARK BLUMENTHAL, Executive Director, American Botanical Council; Editor, HerbaiCram KEVIN ERGIL, M.S., L.Ac., Director and Dean, Pacific Institute of Oriental Medicine NORMAN FARNSWORTH, Ph.D ., Research Professor of Pharmacognosy, University of Illinois at Chicago ADRIANE FUGH-BERMAN, M.D., Chair, National Women's Health Network TED KAPTCHUK, O .M.D., Associate Director, Center for Alternative Medicine Research , Harvard Medical School FRED! KRONENBERG, Ph.D., Director, Rosenthal Center for Complementary and Alternative Medicine, Columbia University ROB MCCALEB, President and Founder, Herb Research Foundation TIERAONA LOW DOG M.D., Department of Family Practice, University of New Mexico WOODSON MERRELL, M.D., Assistant Clinical Professor of Chemistry, Columbia University ROBERT SCHILLER, M.D., Chairman, Department of Family Medicine, Beth Israel Medical Center (New York , New York ) MARCEY SHAPIRO, M.D., Private Practice, Family Medicine and Holistic Medicine, Oakland, California DAVID STUDDERT, J.D., MPH, Harvard School of Public Health VARRO E. TYLER, Ph.D., Professor Emeritus of Pharmacognosy, Purdue University (West Lafayette, Indiana) ANDREW WElL, M.D. , Director, Program in Integrative Medicine, The University of Arizona College of Medicine JACKIE WOOTTON, MEd., Informatics Project Director, Rosenthal Center for Complementary and Alternative Medicine, Columbia University Cosponsored by The Lloyd Library & Museum and ~ERIC-AN BOTfNICAL COUNCIL OCTOBER 17-20, 1997 CINCINNATI, OH

EVENTS & FEATURES: • AHG Members Meeting • Over 35 Workshops & Herb Walks • Tours of the Lloyd Library & Museum • Student I Teacher Kavatail Hours • A.B.C. Bookstore • Tree Farm Recordings 8th Annual Symposium • Herbal Exhibits (Retail & Nonprofit) "Integrating Herbal Medicine into • Saturday Evening Dinner-Dance • Keynote Address by Mark Blumenthal American Health Care" • Herbal Trivia Tournament SYMPOSIUM LOCATION: • Post-Conference Intensives The Vernon Manor Hotel • Day trip to C.G. Lloyd Preserve 400 OakSt • &4!! Onsite Lodging: (800) 543-3999 Featured Speakers: FOR MORE INFORMATION: Call: (541) 488-6260 Keny Bone, FNMH, Mary Bove, N D , Chanchal Cabrera, AHG, Amanda E-mail: AHG97 @aol.com McQuade Crawford AHG, Tleraona Low Dog, MD, AHG, David Hoffmann, AHG, Feather Jones AHG , ?Song, AHG, Ed Smith, AHG, CORPO RATE SPONSORS: ]ill Stansbury, ND, Michael Tierra OMD, AHC, Roy Upton AHC, Matthew Woods AHC, and Donnie Yance AHG Traditional~ Medicinals. Note: Classes begin Friday at 4 : I 5 pm & end Sunday at 6 pm.

Presentations, Protocols, Posters & Plenary Sessions Include: Revitalizing Plant Populations • Pharmacokinetics • GMPs in the Herb Industry • Preserving Your Herbal Library Herbal Internet • Herb & Drug Interactions • Clinical Evaluations • Ayurveda • Kanpo • T.C.M. Herbal Medicine in the Clinic, Pharmacy and Home Herbal • Education: from Community to Correspondence, to Ivy League to Rainforests • Learning from our Eclectic Forefathers • Much more!

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for phytomedicines in the European Union some books are probably not naturally oc­ fications of an official compendium (e.g., a in which plants lacking the sophisticated sci­ curring but are artifactual results of the manu­ national pharmacopei a) and fails to do so or entific data avail able from the research on facturing process of a particular extract from if it fa ils to contain the identity, strength, and leading phytomedicines, as well as herb com­ whi ch they were first isolated. quality that it represents on the label. binati ons with no scientific data to justify He said that feverfew's parthenolide She discussed vari o us aspects of their actions, mi ght receive a traditional content, at least in part, is responsible for the GMPs that deal with batch to batch consis­ claim for some minor conditions. However, release of serotonin. However, he claimed, tency, i.e., Master Production and Control more serious conditions would require the there is no correlation established between Records (MPCR) and Batch Production and more sophisticated drug approval of a com­ feverfew chemistry and the results of two Control Records (BPCR). She emphasized prehensive literature review of the Commis­ clinical studies, because these studies were the need for testing of specified marker com­ sion E or well-controlled clinical studies. done on feverfew leaf, not extract. When pounds in herbal products. Regarding end According to Gruenwald, future legal Dr. Awang worked for the Health Protecti on quality of a product, Zapp stated, "There is a requirements will include the trend toward Branch he was responsible for the require­ critical need in the botanical industry for stan­ international harmonization of botanical ment of a minimum level of 0.2 percent dardized methods and reference materials characteristics. At th e same time there will parthenolide as a standard in order to deter­ [i.e., pure compounds used in the analytical be increased quality in the future and growth mine the proper chemotype, i. e. , as a means testing process] in order to adequately qualify of the total phytomedicine market. Echoing of botanical documentation of commercial products as high quality or poor quality." a point previously made by Prof. Tyler, feverfew products. He noted that there is no Natalie Lazarowych, Ph.D., President, Gruenwald declared that the best-docu­ evidence yet available to determine an opti­ Ashbury Biologicals Inc., Canada, discussed mented botanicals will be used worldwide, mal level of parthenolide content for fever­ stability and shelf life issues, Canadian gov­ at least in the industri alized world. few for human use in the treatment and/or ernment guidelines for stability testing, and Garlic is found in most markets inter­ prevention of migraines. However, implementati on of these guidelines with her nationally. Harunobu Amagase, Ph.D., Se­ parthenolide is extremely unstable when the company's primary product, feverfew. nior Manager, Research and Development herb material is dried. For thi s reason, Dr. There was an entire session on vari­ and Regulatory Affairs, Wakunaga of Awang favors a system of "expiry" (expira­ ous methodological approaches to evaluat­ Ameri ca Co., Ltd., spoke on "Selection of tion) dating of all herbal products, particu­ ing botanicals. Christopher Beecher, Ph.D., Product Dosage Forms for the U.S. Market, larly those with relatively unstable active Associate Professor, University of Illinois­ Technical Feasibility and Consumer Accept­ compounds. Chicago, presented "In Vitro Data as Predic­ ability," in which he presented a detailed ac­ Michael Moore, President and CEO, tors of Human Safety." Activity and toxic­ count of the effectiveness of aged garlic ex­ Li chtwer Pharma U .S., Inc ., discussed ity of compounds subjected to in vitro (test tract (AGE) in various clinical conditions: "Strength Issues and Dosage Form Selec­ tube) bioassays can often indicate activity of cardiovascul ar, anti-oxidati ve, immune tion" of botanical products. He asserted that compounds, but sometimes do not accurately modulation, and overall safety. there is a problem with the variability of what reflect the reality of the biological activity Dennis V. C. Awang, Ph.D., President some products actuall y contain compared to with relevance to human beings. For ex­ of MediPiant Natural Products Consulting their stated label claims. Of 20 commercial ample, quercetin , a ubiquitous compound, is Services, Ottawa, Canada, and formerly garli c products tested under simulated gas­ acti ve in vitro, but does not show the same Head of the atural Products testing section trointestinal conditions by hi s company, he activity in humans after they eat a dinner at the Bureau of Drug Research at Health claimed that nine showed zero effective containing foods that are ri ch in quercetin Canada, spoke on the question of "How yield of allicin, a major sulfur compound in (e.g., onions). Should 'Strength' and 'Dose' Be Determined garlic to which many researchers attribute In vitro bi oassay systems are ex­ for Heterogeneous Botanical Products?" He much of garlic's biological activity. Of six tremely good systems, they are hi ghl y simple referred to feverfew and ginkgo as examples products claiming standardized allicin and specific, but they need to be understood of herbs that contain compounds that are rec­ content, two were allegedl y minimal in in order to make any correlation to human ognizable as active agents. Valerian is one effective allicin release. use. Because they are simplifications of herb whose chemistry is known but it is dif­ Loretta Zapp, President of Industrial more complex human biological ystems, ficult to pinpoint which agents, if any, are Laboratories in Denver, spoke on "Batch to they are limited as to what results can be responsible for activity. Batch and Lot to Lot Variability Issues and gained; onl y about five percent of the results Dr. Awang is an expert on the chemi s­ Dosage Form Selecti on. " She noted that, are applicable when a compound is admin­ try and clinical research on feverfew, so he based on tests conducted by her company, istered to an animal model. focused on this popular herb, where more there are products on retail shelves today that Jerry McLaughlin, Ph.D., Professor of than 80 percent of the total sesquiterpene lac­ do not meet the mandate of Section 7 in the Pharmacognosy at Purdue Uni versity, dis­ tone content is dominated by parthenolide. Dietary Supplement Health and Education cussed "The Use of Bi ological Assays to He declared that more emphasis must be Act of 1994 (OSHEA). This section says that Evaluate Botani cals." Prof. McLaughlin and made on the chemical composition of these a supplement is misbranded and thus illegal hi s research team have developed a number plant materials. A few compounds listed in if it represents that it conforms to the speci- of laboratory techniques to determine the

HERBAL GRAM No. 40 • 45 CONFERENCE REPORT

activity of plant compounds, including as­ A fascinating lecture by Ryan Efficacy Study (DESI), a legally mandated says on brine shrimp, duckweed, potato galls, Huxtable, Ph.D., Professor of Pharmacology, review of drugs required by the 1962 and even yellow fever mosquito larvae! They University of Arizona, dealt with one of the Kefauver-Harris amendments to the Food, have used these methods for over IS years major questions that seems to be on the mind Drug and Cosmetic Act. Over 3,400 sepa­ and have found them instrumental in the stan­ of many health professionals these days, rate drug products were reviewed. The re­ dardization and quality control of bioactive "Assessing Possible BotanicaVBotanical and sults indicated that 40 percent of the drugs components in botanicals. Botanical/Drug Interactions." What evi­ had no effect and 60 percent of the claims Ricardo Faleni, M.D. , Medical Direc­ dence is there that herbs can have either syn­ were not supported. He read from the 1967 tor, Pharmaton SA, Lugano, Switzerland, ergistic or antagonistic actions with other Physician 's Desk Reference some of the spoke on "Dose Response and Botanicals." botanicals or conventional drugs? For ex­ showy language used by drug companies to Central to the challenge of dealing with bo­ ample, senna (and other stimulant laxatives) promote the use of some of the conventional tanicals, he said, is the fact that they are not can produce potassium loss, which can be drugs being sold. Much of these uses were pure compounds and have many components increased by the use of thiazide diuretics. not supported by later clinical trials required and thus may exert simultaneously different This lowered potassium can potentiate car­ by DESI, even after tens or hundreds of mil­ pharmacological activities. He di scussed diac glycosides and antiarrhythmia drugs lions of dollars were spent by pharmaceuti­ some of the problems associated with estab­ when taken simultaneously. Also, the herb cal companies. His thesis: "In Use Data is li shing parameters for optimum dosing in rna huang/ephedra (Ephedra sinica) can have Not Reliable." Regarding "Older Data from clinical testing of tonic or prophylactic a synergistic effect with amphetamines, and Studies," Temple said that older data can be herbs-a point of considerable interest since over-the-counter cold medications such as reliable but it is difficult to know. hi s firm manufactures a leading standardized phenylpropanolamine. He focused on herbal Wayne B. Jonas, M.D., Director, Of­ ginseng extract. He noted that sometimes it safety and noted that there are problems in fice of Complementary and Alternative is difficult to carry out placebo-controlled, assessing adverse reactions, e.g., difficulty Medicine, NIH, spoke about "What Level of double-blind clinical trials for some herb in detecting slow-developing chronic prob­ Scientific Confirmation Should be Re­ because, depending on the dosage form (e.g. lems, in detecting accumulative problems (of quired?" He said that science in the West is tablet, liquid extract, tea), organoleptic con­ the total dose), and in detecting low fre­ hypothesis driven, requiring a reductionist siderations (taste, smell, etc.) sometimes quency events, even if they are serious, also approach. "Perhaps we are sacrificing rel­ make it difficult to keep a product blinded there is still no system for accumulating in­ evance for the rigor." Unlike illnesses plagu­ from the placebo. formation of this type. ing people 100 years ago (influenza, tuber­ Axel Brattstrom, M.D., Ph.D., Medi­ A jocular historical perspective by culosis, epidemics, pneumonia), serious dis­ cal Director, Zeller AG, Switzerland, dis­ John M. Riddle, Ph.D., Professor and Chair­ eases today are more of a chronic degenera­ cussed the subject of "Pharmacokinetics/ man, Department of History, University of tive nature and necessitate new approaches Pharmacodynamics and Botanicals." He North Carolina, dealt with "Pros of Using to looking at the di sease model. Jonas dis­ noted that while these considerations are Historical 'In-Use' Data and 'Older' Re­ cussed problems and limitations of placebo­ important in the evaluation of conventional search Data." Riddle reviewed the history controlled trials which do not estimate the single-chemical entity drugs and can be use­ and use of aloe (Aloe spp.) which he said was overall clinical effectiveness of the treatment. ful for individual components of botanicals, never used as a stand-alone herb (simple) He said that there needed to be a balance there are limits to what significance should when used in Classic Greco-Roman times as between effects testing (e.g., RCTs) and use be placed on these types of studies for bo­ an abortifacient. Aloe, he said, was always testing (e.g., epidemiological and outcomes tanical preparations. Pharmacokinetics and combined with other herbs. Thus, "history information), which sometimes may be suffi­ pharmacodynamics refer to the actual mecha­ of aloe would suggest that it would have a cient for some patients. He made the distinc­ ni sm of action of a particular compound in deleterious effect on pregnancy" when used tion between efficacy as noted in clinical tri­ the human body, to which cellular receptor internally. According to Riddle, "We look als and effectiveness as noted in actual use. sites it binds, how it decomposes into other to the ancients for models for ethics, for Hopefully, this conference was ex­ compounds, the length of time it stays in the beauty, and for other ideas. Why don't we tremely useful for the numerous FDA offi­ body, and other related metabolic informa­ look to them to learn about science too? cials in attendance who are grappling with ti on. With herbs, he says, there are some There is much in the historical record to show the scientific and policy challenges associ­ useful data and some difficulties. For ex­ the safety and efficacy of herbs. No one ated with creating appropriate regulations to ample, for St. John's Wort (Hypericum per­ should market a botanical until they have deal with botanical dietary supplements. foratum), pharmacological studies revealed done a rigorous historical study." Also, members of the herb industry who were reasonable plasma levels of the compound One of the last presentations was given present also benefited from the ideas and in­ hypericin. However, thi s compound is no by Robert J. Temple, M.D., Director, Office formation. As the herb industry becomes longer considered the active ingredient; the of Drug Evaluation I, Center for Drug Evalu­ more sophisticated and research oriented, full extract is now seen to be active, so re­ ation and Research, FDA. He presented the conferences like thi s become essential to the search on an individual component, although other side of Dr. Riddle's argument in "Cons maturation of the industry. No doubt future useful , will not reveal the entire picture. of Using Historical 'In-Use' Data and 'Older' conferences will amplify the topics discussed Research Trials." Temple discussed the Drug in this one. 0

46 • HERBALGRAM No. 40 CONFERENCE REPORT

The Son Francisco Conference of 1996 on Entheogens The Chemical ond Phormocological Actions of Ayohuosca ond lbogoine by Gabrielle Mathieu

HE 1996 CO FERE CE ON E THEOGE S the words of Bl ake, qu oted by Ott, "True reli­ they conquered. However, there was such a (botani cal hallucinogens) was held gion is ecstasy. Everything that li ves is holy." diversity of people that the entheogeni c TOctober 18-20, 1996, at the beauti fuI The lore of the "pl ant teachers" had know ledge was somewhat sheltered. There Fine Arts Palace in San Francisco. The theme different guardians on vari ous continents. In were so many accounts of entheogen use by of the conference on entheogens could be Europe, Christi anity, itse lf originall y a creed Indians of the Americas at the confe rence that summed up in the words of Wade Dav is, based on mysti cal experi ences, evolved into I shall refer to onl y a few. In the Trans-Pecos author of eight books and a fel rmer student a socio-political force inimical to the con­ region of Texas, according to Dr. Peter Furst, of Ri chard Schultes of Harvard, one of the cept of entheogens and self-enlightenment. Professor Emeritus of Anthropology at world's most re nowned ethnobotani sts. In The repression by the Catholic chu rc h was SUN Y, Albany, ew York , ancient tribes the concl uding lecture of the confe rence, mani fes ted histori call y in the attempts of the used the seeds of Sophora secundiflora L. Wade Davis, in a quote fro m his latest book Inquisiti on to eradi cate all other systems of (Ortega) DC Legumin osae, common ly One Rive r, states "Science and myth are beli ef. Thus, the herbal lore of Europe went know n in the south west as the Mountain one." [For more on this book, see cover story underground , kept largely by women, them­ Laurel, in in itiation ritu als. Peyote in HerbalGram No. 38.] selves a di senfranchi sed part of historical (Lophophora williamsii (Lem.) J. M. Co ul t., The study of entheogens is a fasc inat­ Europe. The El ys ian mysteri es of ancient Cactaceae), was also in use, although what ing and intricate venture, demanding a multi­ Greece, alluded to by several of the present­ is know n as th e "peyote cult" in North di sciplinary approach in volving psychology, ers at the conference, were lost, and all that America started much later, in the late 1800s. anthropology, chemjstry, pharmacology, and remain ed of entheogens and communi on Professor Furst showed a slide of a 2,000- botany. Matters are further compli cated by with the spirit world was un fo rtunately at­ year-old ka lima (Indian statue) figurine: it the politics of entheobotany. "Entheogen," tributed to witches who allegedl y worshipped was a hunch-backed dwarf holding peyote. a term coined by Jonathan Ott, organi zer of Satan. (It is interesting to note that what is Dr. C. Manuel Torres, Professor of Art Hi s­ the conference, whose speciality is myco l­ repressed, in this case Paga ni sm, usuall y re­ tory from Florida Intern ational Uni versity in ogy, replaces the more fa miliar term, "hallu­ emerges again in a much less innocous or Miami , stud ies the use of Anadenanthera cinogen," whi ch is politicall y charged. The palatable form .) spp., Fabaceae, a tree that has its pods ground "theo" in entheobotany, the Greek root word In his lecture Professor Josep Fericgla, up to be used in a snu ff. Anadenanthera s for "god," is appropriate. For while the sci­ direc tor of th e In stitut de Pros pec tiva principal ac ti ve ingredient is bufo tenine, ences of anthropology and pharmaco logy Antropologica of Spain , di scussed the uses which has gained notori ety due to its all eged explain the entheogens, it is spirituality that of entheogens in hi storical Europe. Witches presence on th e skin of certain toads. The imbues the traditional use of hallucinogens, used ointments which they said transported oldest ev idence for the use of Anadenanthera and the myths of the cultures that use them them to the Sabbath . Henbane (Hyoscyamus is at a site in the Andes from 2130 B. C. , speak to us in an entirely di ffe rent fashi on niger L. , Solanaceae), was one of the pl ants where it was fo und in a pouch next to a pipe than a chemical diagram. used in the ointments th at witc hes applied made fro m jaguar bones. This is in addition, Traditionall y, in pre-Christi an cultures, directl y onto their sk in or via a wooden of course, to the more commonl y known shamans used entheogens to commune with handle to the mucosa of the vagina with the entheogens such as psil ocybin, used in the gods. As Jonathan Ott points out, the types cl aim th at they could then fl y. Henbane does Oaxaca, and ayahuasca, the potent brew used of cultu res that used entheogens were di ffe r­ produce a feeling of great corporeal li ght­ by many tri bes of South America. Dr. Den­ ent from cultu res with an organized, hierar­ ness, although in actuality the ingestor lies nis Mc Kenna, consultant in ethnopharma­ chical reli gion that in volved a priesthood. in a stupor without movement. Other pl ants cognosy, disc ussed the use (by the Bora, Dr. Lui s Eduardo Luna, professor of in the fami ly Solanaceae such as Bell adonna, Witoto, and Muinane Indi ans of Peru ) of a anthropology at th e Uni versid ad do (A tropa belladonna L. , So lanaceae), were Virola spp., Myristicaceae, which was made Flori anopolis, Brazil , discussed elements of also added. There is even some ev idence, in into a paste. the mystical experience in his presentati on the form of a personal adornment recovered Although most of the presentations on the use of ayahuasca, a traditional me­ fro m this time peri od, th at Psilocybe spp., concerned the Americas or Europe, other dicinal, psychoacti ve blend of herbs in the Strophariaceae mu shroom were used by continents sho ul d not be presumed to have Amazon, whi ch includes the ayahuasca vine witches. no entheogeni c usage. Dr. Giorgio Samorini, (Banisteriopsis caapi (Gri seb.) Morton, In the Ameri cas, where Chri sti anity a research assoc iate fro m the Museo Civici Malpi ghi aceae). A mys ti cal ex peri ence, was not introduced until the Spani sh in vaded in Rovereto, Italy, showed slides taken in which can be ac hi eved through drumming, the New World, there is a ri cher and less oc­ Southern Indi a in the Kerala state region de­ fa sting, and chanting, is facilitated by cult heritage to study, although the repres­ picting stone works erected in the image of entheogens-our "plant teachers." Thus, in sion of the Spaniards did affect the people HERBAL GRAM No. 40 • 47 CONFERENCE REPORT

the fl y agaric mushroom, Amanita muscaria ti cator of the other world ," he also is the one fessor Stacy Schaeffer, Assistant Professor Fr., Amanitaceae. For example, the "hood," who will communicate with other cultures, of Anthropology at The University of Texas as it is call ed in th e Malaylamam language, which are other worlds unto themselves. Pan Ameri can in McAll en, who learned is a stone that resembles the cap of the mu sh­ Luna said the Barquinhas, the third order, are Huichol weaving techniques in order to bet­ room, pl aced over an excavated grave site. very monasti c and fo llow all the prescrip­ ter understand the culture she was studying. Clearl y, the amanita mushroom has reli gious ti ons of the shamans. Dr Ott says that to view the entheogen as a signi ficance in this region as well as in parts Much as these reli gions incorporate trinket, "dope," is debasing to the nati ve sha­ of Europe. Chri sti anity, they are in turn in fl uencing man. But how can we honor entheogens in Western culture again. There are shamans our own culture, given the negative conno­ OW HAVE ENTHEOGENS REMAI NED A in Europe who claim to fo llow the doctrine tati ons of "drugs?" part of the cultures they were fo und of Diame, although there are some questions Several presenters at the conference, H in as those cultures became West­ about their integrity. UDV is a very open although certainly not all of them, seemed erni zed? Often, they have survived in ritu­ religion, built around "nucleos," which seem to feel that they had received insights and als that incorporate Christi anity as well. For loosely equivalent to pari shes. Not all creati vity through their use of entheogens. example, several of the mycologists at the "nucleos" are in Brazil. Some felt that there were "pl ant teachers" conference alluded to the work of R. Gor­ It seems plain that despite the war of who had guided them, others just wanted to don Wasson, who wrote Soma: Divine Mush­ the U.S. government on illicit drugs, a war have fun, most. just chose to give a scientific room of Immortality. Wasson was the first alluded to bitte rl y by ma ny of the presentation and detach themselves from outsider to participate in the shamanistic ritu­ conference's attendees and speakers, the use controversy. For me, a speech by Professor als of the Mazatec Ind ians of Oaxaca, of entheogens continues to exert a fasc ina­ Escohotado of Spain had the most to offer in Mex ico. According to Wasson, the Mazatec ti on on a sector of the popul ation which may the way of insight. shaman ingests Psilocybe mushrooms, and not be enthralled with drugs overall. (I saw Dr. Antoni o Escohotado, Professor of then begins to speak. The Mazatecs consider very little smoking or drinking of alcohol in Socio logy and P olitical Sc ie nce at the sacred mushroom the fl esh of the Gods the th ree days I attended the conference.) Uni versidad Nacional, Madrid, and author with whi ch they take their communion. The Like Richard Evan Schultes, the pioneering of a three-volume treatise on the history of Gods then speak to them. When the shaman Harvard botanist whom many had come to drugs, spoke with wisdom and dignity about eats the mushrooms, he or she recites the honor in their speeches, the speakers them­ the practi ce of taking entheogens. He made names of saints and in vokes the Holy Vir­ selves were a host of contradictions, from a di stinction between inebriety and gin. The "speaking" of mushrooms is Logos, the polite and professori al Dr. McKenn a, clad drunkeness. Inebriati on is a state of exalta­ the expression of the spirit through language in a gray suit, to anthropologist Christian ti on and joy. In ritual inebriation, there is a referred to in the Scriptures, wrote Wasson. Ratsch from Germany, who wore leather distinction between possession and vision­ In Brazil , according to Professor Luna, pants and had long, fl owing hair. ary states. "Possession" is mediated by drugs there are now three religious organi zations Several, such as Ratsch and Jonathan such as alcohol and those in the family Solan­ that use ayahuasca: Diame, UDV, and Ott, seem to think that entheogens are the aceae. "Vi sionary states" are differentiated Barquinh as. They consider themselves future of culture. Dr. Ratsch pointed out in from those by the fact that the participant still Christi an churches, although the use of the press conference preceding the confer­ retains lucidity. Though he or she may have ayahuasca indicates strong Indian beli efs as ence that he thinks the European police have visions, the memory serves as an anchor to well. The churches have been working with so many serious problems on their hands that remind him or her of the distinctions between the Brazilian government to establish the the persecution of people w ho take right and wrong. In heathen cultures, incon­ credibility of taki ng ayahuasca. Professor entheogens will not be a pri ority. He feels veni ence in associati on with inebriants is to Luna recounted hi s experiences in Brazil that participati on in entheogenic rituals ac­ be avoided. Inconvenience consists of clum­ with ayahuasca. While he was with the UDV, tuall y strengthens a sense of community. Dr. siness, insensibility, and greed, all the things (Uni on of the Vegetal, vegetal being one the Ott thinks that "Assuming civili zati on con­ we consider characteristic of an addict. The names used for ayahuasca in Brazil ), he ob­ tinues," Christi anity and other dogmatic re­ preferred state, Escohotado says, is to have served them to have a peri od of strenuous li gions will prosper onl y if they embrace a "sober inebriation," in which the innocence training before ayahuasca ingesti on. There entheogeny. He feels the marri age of "scien­ and playfulness of a person can be released. is fasting and segregati on of the sexes. UDV ti fic hyperm ateri ali sm" and "Judea-Christi an Whether or not we agree with the tak­ has many members drawn fro m the middle dualism" will result in a danse macabre. ing of entheogens by Westerners, it seems class, according to Dr. Dennis McKenna, These are harsh words, but many of we could all respect the moti vati on behind who was a part of a multi-nati onal research these presenters have li ved among the indig­ it: to experience the spirit revealed to us in project in Brazil. The second organization, enous peoples they studied, or, li ke Robert the fo rms from Nature and to feel once again Diame, still has ties to the primeval idea of Montgomery, a speaker and organi zer of the the laughter of our inner child. 0 the forest, but at the same time, the mem­ confe rence, collected rare plants from a re­ [Tapes of 10 presentati ons are avai lable. bers are interested in many modern innova­ gion soon to be deforested. Those who have For more in formati on co ntact Entheo botany, tions, such as the World Wide Web. As Luna li ved among the nati ve populati ons feel pro­ P. 0 . Box 311 , Sierra Madre, CA 91025-03 11 , U.S .A. Phone/fax 818/355-9585.] points out, since the shaman is the "domes- tective of them. This is the case with Pro-

48 • HERBALGRAM No. 40 MARKET REPORT

One-Third of Nation'sAdults Use Herbal Remedies Top Herbal Sources Morket Estimated of $3.24 Billion Pharmacist A. by Barbara Johnston Television A third of the nation's adults (32 percent) NBC Today:Weekend Edition on Saturday, spend an average of $54 per year on herbal March I . Varro E. Tyler, Ph .D., Sc.D., Dean Doctor remedies to treat more common health co n­ Emeritus of the Purdue University School of ditions. According to a national survey co n­ Pharmacy and Pharmacal Sciences and mem­ Health Food Store ducted by Prevention magazine, herbal al­ ber of the ABC Board of Trustees, appeared ternatives have become mainstream. as a part of the presentati on. Dr. Tyler said, That's almost 60 million Americans "I personally am convi nced that so many of over age 18 who use herbs to treat colds, these plants can be very useful products. My burns, headaches, allergies, rashes, insom­ ambition is to see sensible regulations, prop­ ni a, PMS and depression. erl y implemented, that would control herbal The resulting herbal boom has created drugs in thi s country." a $3.24 billion market for botanicall y based Survey results indicate that the major­ health remedies, redefining the herbal user ity of consumers who use herbal remedies 0% 10% 20% 30% 40% from the popular misconception that herbal think they are just as effecti ve, safe, and cost remedies are used by agi ng hippies or fo und efficient as non-herb al remedies. Among onl y in grann y's kitchen cupboard. Botani­ consumers who use herb al remedies, the formation about herbal treatments. The call y based health treatments are becoming majority think they are just as good or better health food store is a source for 13 percent part of a social "norming." th an nonherbal remedies in the areas of effi­ of the nation 's adults, followed by doctors This growing use of herbal remedies cacy (53 percent), safety (65 percent) and (9 percent), television (5 percent), and phar­ was the subject of a segment on television's cost (58 percent). Two in five Americans macists (4 percent). (42 percent) think that herbal rem­ This information is based on a nation­ edies can effectively treat ill nesses wide telephone survey conducted for Preven­ like cancer. tion magazine by International Communica­ Friends and family, and not tions Research (ICR). Interviews were com­ necessaril y the health food store, are pleted with a full probability sample of I ,008 Over$ 100 t:3] the sources most people use to learn adu lts age 18 or older fro m February 7- 11 , about herbal remedies. Forty-one 1997. The margin of error is plus or minus percent of Americans hear about 3.3 percentage points. 0 $51.1 to $1 00 herbal remedies through the grape­ [Prevention. 1997. Survey on Use of Herbs in vine, 37 percent turn to magazines, America. Rodale Press, Emmaus, Pennsylva­ $20.1 to $50 and 35 percent consult books for in- nia.]

$20 or less Leading Uses of Herbal Remedies Zero 21% menopa use 0% 10% 20% 30% 40% diarrhea -u::::==:::/1

Herbal Remedies Better or Same in Consumers' Eyes 1 v Safety ~ a I I l {'

v 7 CosI ~ / I ~~ i '_ -o v Effectiveness ' v ,r ·~ a / 0% 10% 20% 30% 40% SO% 60% 70% 0% 10% 20% 30% 40% 50% 60% HERBALGRAM No. 40 • 49 MARKET REPORT

Today's Proactive Consumer and Herbal Supplements

by Leonard Wood

To truly understand the dynamic growth in "food ingredi ent avoidance" as the way to thritis. And just like other leaps in attitudi­ herbal supplement use that has taken place improve health. Since the leap, fats have be­ nal change, we are in the early phases of over the past several years, it is important to come the focus of avoidance and remain so learning. Vitamins, particularly antioxidant understand the broader context of how con­ today, although there are signs of change. vitamins and herbal supplements, have been sumer attitudes toward the relationship be­ The late 1980s and early 1990s saw consum­ the focus of today's "proactive consumer." tween health and diet have been evolving ers becoming much more knowledgeable It is important to understand that we are in and the sea changes that have been taking about nutrition and the relationship between the early stages of learning and that Ameri­ place in these attitudes during the 90s. Our diet and health. The food pyramid and the cans are likely to take action now and sort Gallup studies have been monitoring Ameri­ concept of a balanced diet have been par­ out the details later. This is undoubtedly the can nutritional attitudes and food habits since ticularly important in this transition. case driving the recent surge in herbal supple­ the 1970s. The food pyramid has become a ment use. For the herbal supplement indus­ The late 1970s and early 1980s were well-known symbol of balanced eating. In try, the devil is likely to be in the sorting out dominated by avoidance behavior-what our 1993 Gallup Changing Food Prepara­ of the details and I am afraid that herbal food should we try not to eat-and much of tion & Eating Habits study, about one-fourth supplement marketers are not off to a good thi s early "avoidance behavior" was focused were aware of the pyramid, doubling to one start. on preservative ingredients in processed food in two (51 percent) in the 1996 study, and it Our 1996 study of herbal supplement that were potentially carcinogeni c. In our is a good example of a more nutritionally users found that most of the growth in herbal first Gallup Study of "Changing Food Prepa­ knowledgeable consumer. supplement use was coming from "first time ration and Eating Habits," conducted in A more nutritionall y savvy consumer, tryers" and compared to the more traditional 1977, the ingredient meal preparers most aging baby boomers coming to grips with users, they were frequently mentioned as a concern was red their own mortality, and publicity about the • more li kely to have purchased their dye No.2. Today few consumers think about potential of antioxidant vitamins to possi­ supplements in a supermarket or drug red dye No. 2 or any other additive. Con­ bly prevent cancer, heart disease, and slow store vs. a health food store; cern soon moved on to other ingredients such aging, have been the catalysts for the next • more likely to be light users of herbal as salt, sugar, and cholesterol, triggering the evolutionary leap-a shift in focus from supplements and less likely to also be food industry's development of low salt, "What foods can do to me to what foods can taking vitamins; sugar-free, and cholesterol-free products. It do for me." (Fig. I) • Ginseng is the most popular supple­ was during this time that the vitamin and With thi s shift has also come "new ment among new users. mineral supplement industry experienced expectations" of what food and nutrition can significant growth. do for consumers, ranging from more en­ Changes in American attitudes and ergy and stress re li ef to eliminating the behavior have hi storicall y taken place symptoms of menopause and help with ar- through what can best be described as a process of "leap and learn," and this fiGURE certainl y appli es to evolving nutritional atti- tudes and habits. Con- su mers became increas- ingly aware of the rela­ tionship between diet and health in relation to heart disease, cancer, hi gh blood pressure, etc., and at least in concept if not in practice, embraced

SO • HERBALGRAM No. 40 MARKET REPORT

Perhaps more importantly: lations for food and supplements and is look­ readily available. As use becomes wide­ they are less likely to be knowledgeable ing for specific benefits (e.g., more energy, spread and new users buy their herbal supple­ about herbs than long-term users and pain relief, etc.). In many ways the expecta­ ments from supermarkets and drug stores they are concerned about the effective­ tion bar has been raised and supplement where knowledgeable advice is less avail­ ness and safety of the supplements marketers have responded. Unfortunately the able, the need for education becomes even they are trying. less knowledgeable and skeptical new users more important. can be easily disappointed if near-term re­ While the likelihood of benefit claims Recent publicity and product advertis­ sults do not live up to expectations and leading to disappointed consumers and other ing has been successful in attracting new claims. marketing mistakes is high, it is also likely users and expanding the market, but can In a recent series of focus groups con­ that use of herbs, whether from supplements, supplements li ve up to expectations? ducted on Positive Nutrition, I was surprised the fortification of foods and beverages, or Our annual Gallup studies of the vita­ to hear the extent of the strong negative re­ from fresh produce, will grow in the years min and herbal supplement markets have actions to the cost of herbal supplements. As ahead. These products fit so well with the shown growing consumer interest in both vi­ one man in Chicago put it, "It's as expensive proactive approach to nutrition and health ob­ tamins and herbal supplements, with vita­ as can be! I went to a health food store, and served today, that they are likely to be with mins showing steady growth in usage dur­ someone showed me a bottle. It was s us for some time in the future. The aging ing the 90s, while the growth in herbal month's supply and it was forty bucks. I said baby boomers could be a strong potential supplement usage has been more dramatic, 'forget it. ' I'm just going to buy better food market in the years ahead as they cope with particularly over the past year or so. Pres­ at the grocery store." age-related health problems and their quest ently, about one adult in five is using an The perception of herbal supplements for ways to slow the agi ng process. 0 herbal supplement-about half the propor­ as expensive tends to raise the expectation tion of adults that are currently taking vita­ bar even higher. Leonard Wood, President ofMulti- sponsor mins. Among herbal supplement users, about Several observations from the group Surveys, In c. , in Princeton, New Jersey, has over two thirds (54 percent) are also taking vita­ sessions may identify key factors affecting 25 years experience in assessing public behavior mins and mineral supplements. (Fig. 2) herbal supplements' future growth: and altitudes concerning food and nutrition. Multi-sponsor Surveys, Inc., conducts the Gallup Vitamins and mineral supplements Of the barriers to future growth, the syndicated surveys in the food and nutrition ar­ have traditionally been viewed as helpful for need for more information may be most im­ eas under a licensing agreement with The Gallup long-term health benefits and general over­ portant. The traditional herbal users took the Organization, In c. all nutritional benefits. As discussed, today's time to study and typically shopped at a more proactive consumer has greater expec- health food store where advice was more ... today's fiGURE 2: VITAMIN USE AMONG HERBAL SuPPLEMENT UsERS more proattive

Take herbal supplements only tonsumer has 36% greater expettations for food and supplements and is looking lor 64% spedlit benefits. Take herbal supplements and vitamins

HERBALGRAM No. 40 • 51 MARKET REPORT

Whole Foods Magazine's2nd Annual Herb Market Survey for U.S. Health Food Stores

The results of the second installment of the beauty care products. standardi zati on in herbal products" each at Whole Foods Natural Herbal Products Sales The top five herbs accounted for 33 5 percent, and "prices of herbal products" at Survey are in ; 1996 was a wonderful year percent of herb sales, with the top ten ac­ 2 percent.- Barbara A. Johnston for herbs, with herb sales up significantl y counting for 49.7 percent, or nearl y half, of [Ri chm an, Alan, and James P. Witkowski. A since the survey was first conducted in 1995. herb sales. Newcomers to the top ten list Wonderful Year for Herbs. Whole Foods, Oc­ Approximately 200 natural foods/ were psyllium and cascara sagrada. Beyond tober 1996, 52-60.] products stores responded to this survey. the top ten are cayenne at 2.5 percent, aloe Overall sales at the "typical" natural foods/ at 2.4 percent, valerian at 2.2 percent, eat's products store have continued to increase claw at 2.1 percent, grape seed extract and since 1995, with virtually all the growth primrose oil tied at 2.0 percent each, dong Herbalife Tops $1 Billion emanating from the strength of the herbal quai at 1.8 percent and each of the following products category. Respondents to the 1996 herbs at 1.7 percent: pau d' arco, ginger, cran­ The Los Angeles-based Herbalife Intern a­ survey report that herbal product sales are berry, milk thistle, and yo himbe. tional Inc. (Nasdaq:HERB) reported in Feb­ up from 20.5 percent of total store sales to Asked to name three herbs that they ruary that it ac hieved record retail sales of 27 percent of total sales. This includes herbal thought would have "significantly increased $1,200, 144,000, net sales of $63 1,935,000 supplements, herb-content food and bever­ impact in 1997 ," respondents noted eat's and significantly improved earnings for age products, and herb-content health and claw as the most promising "up-and-com- 1996, which more than doubled from I 995. ing" herb. Interestingly, despite the Net income for the 1996 fourth quarter in­ fact that it was also elected the num­ creased to $ 13,830,000, or $0.42 per share Sales Of Herbs in Health Food Stores -1996 ber one up-and-coming herb for (fully diluted), up 175 percent from 1996, this herb actually went down $5,037,000, or $0.17 per share, in the corre­ Percent of Ranking in rank of herbal supplement sales sponding period a year ago. toto/sales in 1995 during that year. The other nine top Net income more than doubled in 1996 1. Ech inacea 9.6 % 1 ten up-and-coming herbs named for to $44,791 ,000, or $1.38 per share, from 2. Garlic 7.2 2 1997 are, in descending order: $19,728,000, or$0.65 per share, in 1995. Net 3. Ginseng 6.4 4 echinacea, ginkgo, kava kava, saw sales for the year rose 29 percent to 4. Ginkgo 5.1 5 palmetto, bilberry, elderberry, gold­ $631 ,935,000, over $489,004,000 in 1995, 5. Goldenseal 4.7 3 enseal, grape seed, and wild yam. while retail sales advanced to a record 6. Mahuang 3.8 8 In the area of obstacles that $1,200,144,000, compared with 7. Psyllium* 3.5 not listed stand in the way of greater herb $923,644,000 in the prior year. 7. Siberian ginseng* 3.5 9 sales success, the number one re­ 8. Saw palmetto 3.1 6 Major factors contributing to the 9. Cascara sagrada 2.8 not listed sponse (41 percent) was "lack of company's full-year results include retail consumer education about herbal sales in the Asia/Pacific Rim region, princi­ *tied products," and in second place (23 pally Japan, of $378,785,000 in 1996 vs. percent) was "government restric­ $143,494,000 in 1995, an increase of 164 tions on information available to percent. Sales in Europe in 1996 were consumers." After these two came $43 1,347,000, 15 percent increase over 1995 the following: "scare stories about sales of $373,946,000, reflecting strong re­ herbs in the consumer media" at 18 tail sales in Russia and Poland. The Ameri­ percent, "competition from mass­ cas region was down four percent from 1995. market outlets" at 6 percent, "in­ Herbalife International markets sufficient manufacturer promotion weight-management products, nutritional, of herbal products" and "lack of food and dietary supplements, and personal care products in 34 countries worldwide. Herbalife products are available only through a network of independent distributors and di stributor supervisors who purchase the Echinacea, Echinacea products directly from the company. 0 purpurea. Photo © 1996, [Press release. Business Wire. Feb. I 8, 1997 .] Steven Foster.

52 • HERBAlGRAM No. 40 MARKET REPORT

by Peter Landes

SPICES: Except for the tropi cal spi ces, addition, will certainly start to mold within there anyone out there not growing which are generall y harvested during the 48 hours. The Mace, whi ch surrounds and Echinacea?) It is easy enough to figure out North American winter, markets have turned protects the Nutmeg, will , of course, be af­ where the particular herbal ingredient you dull in the previous quarter. Tropical spices, fected first so, as a con equence basically of seek is in the market cycle by price, quality, such as Black & White Pepper, have contin­ a price that is too low for too long, utmeg and amount of suppliers desperately trying ued their upward price march, seemingly is available, Mace is not. Temperate cli­ to sell it. without relief from a normal-sized Indian mate spices, Oregano, Basil , Marjoram, As an effect of burgeoning demand, crop which came on stream in November/ Mints, etc., are just coming on at this time. even the "regul ar" botanicals are very ti ght December. The White Pepper crop comes on Crops are predicted to be normal, so prob­ in supply and will remain so fo r the foresee­ in July/August in Indonesia and may have a ably another year of incredibly cheap spices able futu re. Early and regular coverage is moderating effect on the rapid rise in price is in the cards. Fennel Seed, on the other necessary to obtain good-quality supply on seen during the past year, but no major relief hand, was short last year from Egypt and a timely basis and good communication be­ is expected since the crop is rumored to be while the March crop from India provided tween sales/marketing and purchasing de­ low normal in size and other origins like Ma­ some relief it is just not as clean as the Egyp­ partments are key to anticipating increased laysia, China, and Brazil are uncompetitive. tian because of a lack of color-sorting ma­ demand. The real key is to maintain good We have noted increased demand for Tur­ chinery in India. The Egyptian crop coming contact with reliable suppliers. meric, which has risen in price due to the in June/July is anxiously awaited. More on usage of Curcumin as an antioxidant. Gin­ thi s in our next exciting Market Report. POTPOURRI INGREDIENTS: Very ger, too, has seen price increases from its very dull markets. Lots of good material avai l­ low levels at new crop time (February/ BOTANICALS: In Spices, demand is able at very advantageous prices. Will the March). Nutmeg is up about 10-15 percent hardly ever a price factor since people won 't "too cheap for too long" rule prevail here'1 in price and is in somewhat short suppl y. use more Pepper, for instance, if it's "cheap," Let's wait and see! (These markets are so dull Mace remains extremely scarce­ or less if it 's "expensive" (at least not in the that this is an exact repeat of last Market mostly unavailable and exceedingly expen­ First World). In Botani cals demand is very Report comments!) 0 sive. This is odd since, as botanicall y savvy much the major factor and market mover and readers will remember, both spices are made demand has exploded in the last few years. from exactly the same fruit of the Nutmeg This has led to many boom-and-bust cycles tree-so how could one be so much scarcer in the cultivation and marketing of these eso­ than the other? Well , it seems that Nutmeg teric, problematic items. Demand comes on has been too cheap to bother much about for very strongly and very suddenl y, sometimes quite a while. The Nutmeg fruit looks very in response to an article in a major publica­ much like a peach; the Nutmeg is the seed, tion like the one on St. John 's Wort in or pit, and the Mace is a seed covering which Newsweek, or a TV feature on the evening surrounds the utmeg-like tendrils. There news, or an infomercial on TV or radio, or are, of course, two ways to harvest a ripe even Blumenthal's shameless promotional fruit: climb the tree in the tropical heat and efforts on the industry's behalf-who humidity of Indonesia and pick the fruit knows? Good-quality supplies are generally (whi ch is how it's done when there's good limited and the market is emptied out in days, money in Nutmeg), or wait until the fruit falls sometimes hours. The scramble begins. to the ground from its own weight and then Prices for even low-quality goods skyrocket go pick it up. This second way is how it's and companies end up paying hi gh prices for been done now during the previous period poor material. Next, lots of specious or ba­ of low price and oversupply. The fruit falls sically valueless material comes on the to the ground, splits open, and laborers then market and even that is scooped up by unso­ separate the Nutmeg from the Mace. Unfor­ phisticated users. Growers/gatherers are Black Pepper, Piper nigrum . tunately, anything sitting on the ground in encouraged by the extremely high prices and Photo © 1994 Steven Foster. Indonesia (including you) will soon be in­ seemingly limitless demand and good mate­ fested by the astoundingly huge and healthy rial is oversupplied just as consumers move insects of the Indonesian archipelago and, in on to the next "hot" herb. (By the way, is

HERBALGRAM No. 40 • 53 BOOK EXCERPTS

Plants, People, and Culture: The Science of Ethnobotany by Michael J. Bolick and Paul Alan Cox

Walk into any pharmacy in the United States, Canada, or Western Europe and ask to examine any bottle of prescription medicine chosen at random. There is a one-in-four chance that the medicine you hold in your hand has an active ingredient derived f rom a plant. Most of these plant-derived drugs were originally discovered through the study of traditional cures and folk knowledge of indigenous peoples-the ethnobotanical approach.

HIGH MEAT CONSUMPTION, LOW almost exclusively on the meat, mil k, and they are di ssolved in water. The implicati ons CHOLESTEROL LEVELS, AND blood prov ided by their cattle, a nutritional of th is research are profound: if new INDIGENOUS PLANTS: NEW LEADS regi me that the New Scientist has call ed "the cholesterol-lowering substances can be iso­ FROM KENYA world 's worst di et." Although the Batemi , lated fro m these wild-gathered plants, mil ­ The Masai and Batemi are cattle- herding as agropastorali sts, do not depend on meat li ons of people could reduce their ri sk of car­ peoples of Kenya and Tanzani a, numbering as heav il y as the Masai, average members di ovascul ar illness, th e gravest health over half a million in the most recent cen­ of these tribes ingest up to 2,000 milligrams th reat in th e Western world. sus. ln traditional settings, the Masai li ve of cholesterol a day- well over the max i­ As the Akimel O'odham Indians, th e mum recommended da il y intake of 300 mil­ Au strali an Abori gines, and the Masai and li grams. Yet, remark abl y, their blood cho­ Batemi of East Africa have demonstrated, a lesterol levels are low- about one-third the Western di et poses a grave threat to more th an cholesterol level of the average Ameri can. Western ers. Throughout the worl d, indig­ Researchers have long argued th at these enous peoples are increasing their consump­ peoples must have speciali zed genes that ti on of Western foods. In some societi es, prevent them from succumb ing to what oth­ such as Samoa, imported foods such as erwise appears to be a sure prescription fo r canned corned beef have acqui red significant arteri osclerosis and res ul tant cardi ac di sease. soc ial presti ge, but we now know that the The supposition of a geneti c respon se hi gh fat and sodium levels of Western diets to a hi gh-cholesterol diet does not, however, are con·elated with increased tri glyceride lev­ account fo r the hi gh cholesterol levels found els, coronary disease, obesity, and diabetes. in Masai and Batemi who move to Nairobi and switch to a Western diet. Ti moth y John s, an ethn obotani st at ISOLATION OF THE ANTI·HIV DRUG McGill Uni ve rsity, has studi ed a vari ety of FROM A SAMOAN TREE wild-gathered tree barks that the Batemi and Samoan medicine diffe rs signi,ficantl y fro m Masai people add to their meat. Typicall y Western medi cine in its descriptions of dis­ they boil meat slow ly in milk , stirring the ease eti ology. Many di seases recogni zed in bark of Acacia goetzei [Mimosaceae Samoa are not directly translatable in to West­ The American botanist John W. Leguminosae] and Albizia anthelmintica ern terminology. Samoan healers refu se pay­ Harshberger coi ned the term [Mimosaceae Leguminosae] and other trees ment fo r their services, arguing that the pl ants "ethnobotany" in 1895 to describe into the broth . They do not use these barks are a gift of God. Yet their kn owledge is stud ies of "plants used by primitive and as fl avorings in other foods, so Johns began formidable: a typical healer can identify over aboriginal people." His 1896 200 spec ies of pl ants by name, recogni ze publ ication, The Purposes of to suspect that the barks might play a more Ethnobotan y, is generally accepted as a sophisti cated role: perhaps they serve to over 180 disease categori es, and compound starting point for thi s field as an lower blood cholesterol. With hi s coll eague more than I 00 remedies. academic disci pl ine. Photo by the Laurie Chapman, Johns tested the barks and When a healer di agnoses a di sease that Marceau Studios, Ju ne 20, 1913. Ph oto fo und ev idence that they do reduce blood req uires an herbal treatment, she immedi ately courtesy of The University Arch ives and cholesterol, possibl y because they contai n begins to co ll ect the necessary plant materi ­ Records Center, The University of unique saponins, organic compounds with a als, since onl y fresh plants are used. Most Penn sylvania , Philadelphia, PA. sugarlike core that fo rm a soapy foa m when treatments are prepared using a combinati on

54 • HERBAL GRAM No. 40 BOOK EXCERPTS

of several species of plants gathered in the Cox then carried the freeze-dried wild, but some remedies are prepared from samples to the NCI in Maryland, a single species. where a team including Mi chael Consider the treatment that Epenesa Boyd, John Carde llina, Kirk Maui goa uses for fiva samasama (fiva = fe­ Gustaffson, Peter Blumberg, John ver; samasama =yellow), the clinical mani­ Beutl er, and oth er researchers festati on of ac ute hepatiti s. After confirm­ tested them fo r acti vity against the ing a diagnosis of fiva samasama, Maui goa HI V- 1 virus- the viru s associated has one of her children journey to the forest with acqui red im munodeficiency fo r the wood of the mama /a tree sy nd rome (A IDS ). ( Homalanthus nutans [Euphorbi aceae]). But The NCI team soon fo und not any type of mama/a will do; botani sts th at the stem wood extrac ts ex hib­ recogni ze one species of Homalanthus, but ited potent in vitro ac ti vity again st Maui goa recognizes two. "Only the mamala the HlY -1 virus, both stopping the with long white petioles is used," she ex­ virus fro m infecting health y ce ll s pl ain s. The mama/a with red peti oles on the and preventing in fected human cell s fro m Top : Jul ie Chinnock, an ethnobotanist w orking w ith a Ke kc hi Maya shama n in leaf is reserved for abdominal complaints dying. Bioassay-guided frac ti onati on re­ the Punta G orda reg ion of Belize, prepares called tulita saua. sulted in th e iso lati on of pros tratin pla nts used to treat diabete s. Th e shaman Maui goa scrapes away the outer cork ( 12-deoxyphorbol 13-acetate). had desc ribed the preparation and use of and epidermal ti ssues of the wood and ex­ The identi ficati on of prostratin , which the plants to a med ical doctor working as tracts the "inner bark," or cambial ti ssue, by belongs to a group of compounds known as part of a team w ith Chinnock. scraping it with a kni fe . She pl aces the ph orbol s, as the ac ti ve co mponent in H. Above : The interior of an Ayurvedic scrapings in a cl oth, ties it like a tea bag, and nutans caused some concern : phorbols are med icine sh op-in th e town of Kottakkal, immerses the bag in boiling water for half kn own tumor promoters. Research co n­ Kerala State, in southern India-shows the an hour. After remo ving the bag and di s­ ducted by a team led by Peter Blumberg at vast array of products available for thi s carding its contents, she filters the liquid NCI demonstrated that prostratin does not system of traditional medicine . Photos courtesy of M ichael J. Bo lick, New th rough a cloth and gives it to the pati ent to promote tumors, even th ough it ac tivates pro­ York Botan ical G ardens, Bro nx, NY. drink. tein kinase C, a typical indicator of tumor promoti on. Indeed, the NCI team fo und that In 1984 Epenesa Maui goa and other AVAILABLE FR~ - -~-~ healers told Paul Cox about thi s remedy fo r prostratin functi ons as an anti promoter: it fiva samasama. Gordon Cragg of the Natu­ stops mutant cells from developing into tu­ ABC'S HERBAL ~. .'.::,',' ;,-:=::' ral Products Branch of the Nati onal Cancer mors. The NCI is currentl y so li citing bids EDUCATION CATALOG -·-- Institute had ag reed to evaluate th e pharm a­ from drug companies to li cense prostratin for PLANTS, PEOPLE, AND CULTURE cological efffi cacy of medicinal pl ants th at drug development. Since prostratin stops by M. Bolick and P. Cox. 1996. Beginning Cox mi ght find in Samoa, and among the cell s from becoming infected with the HIY -1 with the prehistoric use of plants by materi als he coll ected were stem wood viru s and prolongs the li fe of infected cell s, hunter-gatherers and the development of samples of H. nutans. Attempting to simu­ it may pro ve to be etlec ti ve as part of a com­ agriculture, the authors reveal how studies of plant use by late traditi onal preparati on techniques, he binati on therapy in tandem with proteases indigenous peoples is the key to understanding the history of human civilization . Intriguing firsthand stories of fie ldwork in chose not to use the standard method of air and other anti viral compoun ds. Yet toxicity remote villagesdeep in the rainforests of South America, drying to prepare samples for analysis, but may be a problem. Although prostratin has Africa, and the islands of the South Pacific reveal the vast in stead re turned to hi s laboratory in the give n no signs of promoti ng tumors, as a amount of knowledge indigenous peoples possess that United States with the samples preserved in phorbol it is a member of a ve ry tox ic group warrants preservohon . Hardcover. 228 pp. $32.95 . #B196 aqueous alcohol in aluminum bottles. In hi s of chemi cals. Onl y careful tox icolog ical See th e center of th is issue for order lab he removed the alcohol in a rotary evapo­ studies will determine if prostratin can be form and over 300 other books, or rator and pl aced the extracts in a freeze drier. safely adv anced to human clinical trials. 0 phone 800/ 373-7 105

HERBALGRAM No. 40 • 55 IN MEMORIAM

D r. E. H. Bronner 1913-1997 Dr. E. H. Bronner, an 84-year­ 1960s. He was jailed after speaking against communism and fluori­ old, third-generation soap­ dation, and has spent small fortunes in support of rain forests as well maker passed away from ad­ as sending long telegrams to world leaders, and helping the needy. vanced Parkinson's disease in He was blind for over 25 years, but did not feel it was a handicap. March 1997. Dr. Bronner is Dr. Bronner's story was featured on many talk shows and in articles famous for hi s Peppermint 18- in many publications including Esquire Magazine, the Wall Street in-1 Pure-Castile Soap as well Journal, and Gentleman s Quarterly. A portion of profits from his as 25 other products esteemed business goes to planting trees, helping homeless shelters that assist by backpackers and ecologi­ people to find work, and a fresh water well project in Ghana. An cally minded folks . The soap excerpt read at his funeral expresses his life perfectly. "It will prob­ carries on the label a 3,000- ably never be clear whether it is the soap or the message on the word philosophical message bottle which has made Dr. Bronner's more than a product, but a with print so small that it takes symbol of an ideal, an ideal product. The doctor himself might say a magnifying glass and half an it was faith in his loving God of all mankind and all the good karma hour to read. Dr. Bronner billed accrued from fighting the good fight. Whatever the reason, Dr. himself as a senior Rabbi and master chemist amo ng other things. Bronner's soap business is testament to the fact that upstanding ideas Fans were delighted to learn that, unlike Dr. Pepper, he was a real and pure and natural ingredients can indeed ensure success. Dr. person, a persistent man who endured the lean years until hi s home­ Bronner will leave this world a better place." - Barbara A. Johnston made soap bloomed into a multimillion-dollar business in the late

EnJoot onty 2 COimltiCI,IftOUgh siHp I Dr. Brannlr's 'MifiC Dr. Bronner's PEPPERMINT 18-in-1 So1p' to clean body-mind-soul· Cottll~• : ~"~••111m Solvlloll, Cato!IIII.Ohe.J.tt-.~ 1 111 Ols spmt instantly uni1ing Qnet All­ One ! Absolute cleanliness tS GodVne ss1For lacialpacks. scatp PURE-CASTILE SOAP & soothtng body rub. add Cash Always dilute IDJ Shne·SIIIIflpOO ·MISIIGI·Dentii·SOIP 81th! onDathtOolo'elinsir»:olholwater. Peppermtnt •s nature 's own unsurpa ss ed fragrant deodorant! Wong out lay over face & scalp. 1% & 99% hot wate r "' tacill p.ck, s~mpoo, hair condllionef1 Massage with fingertips. Repeat 4 A aash in glass water = breath frnhenlng Pepper mmt Soap! 3or4times 'trl arms. l.egs &alt 5 For muuge, Chlute 1 part tn 10 pa rts hot water• Not oill are rubbeO. always towards the 6. Apply Peppe rmmt Soap dry. to cle an anl·mosqwlto·lltk·flyl heart Rmse to.wl m plitn hOI 7 Otl ute with hot water to t itan & lreslle• lrtm ftlad to 1111 water ana massage again. 8. Peppermmt Otl Soa p for Dtspennrs·Un itorms-hllly-Bncht Breathe deep!~ Health is Wealth. 9 3 Cashes m wa ter 11 ose most Sprrys ott lryit & YIQIIIblest Within9mtnutes)'OUietl1resh. 10. 2% soap m water spr1ys -cluns flowers & fruit trees! mrnt-clean . saving 90% ol your hOI water & soap. ready to help teach the whOle Human race the Moral ABC ol All-One -God ­ faith! Forwe"re AI-OneOfnone! All-ON E1 All·ON E1 All-O NE'

56 • HER BALGRAM No. 40 IN MEMORIAM

Christopher Hills, Jr. 1927-1997 Microbiologist and visionary Christopher Hills, Jr., who helped pio­ A self-made millionaire neer the health food and human consciousness movements, the from hi s early entrepreneuri al founder of "Life Force" Spirulina, died at hi s home in January after days, Hills moved to Boul der a long illness. Creek in 197 1, where he be­ Hills was co-discoverer of the protein-ri ch pl ankton spirulina, gan to expl ore human con­ the base for many natural food products, and fo unded the Uni versity sciousness. In 1973 he of the Trees in Boulder Creek, Califo rni a. founded the Uni versity of the "He wanted to reach out and solve the Earth 's problems and at Trees in Boulder Creek, an al­ the same time, he wanted to promote higher consciousness," said tern ati ve education and re­ hi s wife, artist Penny Slinger Hills. "He was a dreamer of impos­ search center for the social sci­ sible dreams but he made a lot of those dreams come true." ences speciali zing in the study Hills, a nati ve of Grimsby, England, co-discovered spirulina of the laws of nature and how in 1966, then traveled the world touting the plankton as a superfood they re late to human con­ capable of solving the world's hunger problems. scio us ness. He wrote 30 In 1965, the Hills family moved to London and founded the books, selling mi ll ions of copies worldwide. spiritual community known as Centre Housem and, in 1970, Chris­ Hills is surv ived by his wife, two sons, and three grandchil­ topher organi zed and became President of the first World Confer­ dren. - Barbara A. Johnston ence on Scientific Yoga, in Delhi.

William McKinley Klein, Jr. 1934- 1997 William McKinley Kl ein, Jr., the dynamic botani st who made a ca­ run-down garden into a bustling reer of leading and transforming botanical gardens from quiet gar­ showplace with a budget of $2 dens to centers of ac ti vity, died of heart failure in Coral Gables, million. Florida, Wednesday, February 12, 1997. He was 63. A fervent collaborator, For the last three years, Dr. Klein had been president and chief Klein organized Philadelphia gar­ executi ve officer of the National Tropical Botani cal Garden of four dens into the Philadelphia Gar­ gardens in Hawaii and one in Coconut Grove, Florida. From 199 1 dens Collaborative fo r joint mar­ to 1993 he had been director of the Fairchild Tropical Garden in keting and publicati ons. A gifted Miami and director of the Morris Arboretum of the University of and prolific writer, Klein also was Pennsyl vani a in Philadelphia from 1977 to 199 1. the author of Gardens of Phila­ Klein and his wife, Janet, moved to the island of Kauai in delphia and the Delaware Valley, Hawaii in 1994, where he set about the task of opening the a comprehensive and poetic guide organizati on's gardens-closed due to extensive damages from Hur­ to the gardens of the region. ri cane Ini ki in 1992. Within two years, Allerton and Limahuli Gar­ When Hurricane Andrew deci­ dens on Kauai were open to public tour. Lawai Garden was sched­ mated Fairc hild Tropi cal Garden ul ed fo r tours thi s spring, Kahanu Garden on Maui opened in Janu­ in Mi ami in August 24, 1992, ary by appointment, and The Kampong was draftin g plans for pub­ while he was director, Kl ein led li c programs. Dr. Kl ein also increased the scientific staff from two restorati on efforts, in vited sc ientists from around the world to capi­ to seven Ph.D.s, because he was emphati c about the need for the tali ze on the opportunity to take samples from fe ll ed rare trees, Garden to emphasize research in the biology of tropical plants. and even sold the harvested rare woods for fund-raising. He re­ Dr. Kl ein received his bachelor's degree in range science for­ opened Fairchild on October 3, 1992, although 60 to 70 percent of estry from Colorado State Uni versity in 1955, and hi s master's de­ the garden's coll ections had been severely damaged. gree in botany, also from Colorado State, in 1957, and hi s Ph.D. Dr. Kl ei n's ability to make others see hi s vision of the im­ from Claremont Graduate School. Hi s career started in academi a, portance of plants and research was one of his greatest strengths. as an associate professor of the Department of Botany at Colorado He is survived by his wife, fou r children, hi s mother, and State Uni versity. two sisters. The fami ly requests that contri butions be made in hi s In 1972 he became assistant to Dr. Peter Raven, the promi­ memory to th e ati onal Tropical Botani cal Garden (P.O. Box 340, nent botanist and director of the Missouri Botani cal Garden. In 1977, Lawai, HI 96765) and the Morri s Arboretum ( I 00 Northwestern Dr. Klein was appointed director of the Morri s Arboretum in Phila­ Avenue, Philadelphia, PA 19 11 8). - Brad Bennett, Ph .D. delphia, which was transformed under hi s directorship from a quiet,

HERBALGRAM No. 40 • 57 IN MEMORIAM

James Chester Raulston 1940- 1996 Benny Simpson James C. Raul ston, Ph .D., director of th e arboretum at North Carolina 1928- 1996 State Uni versity in Raleigh, died Benn y Simpson, a researcher at in an automobile accident in De­ Texas A&M Uni versity's Re­ cember 1996. Raulston was one search and Extension Center in of the university 's leading teach­ Dall as, di ed in December 1996. ers and , 20 years ago, was in stru­ Simpson , a frequent lecturer at mental in the transformation of an th e National Wildflower Re­ eight-acre patch of campus into a search Center in Austin, was born coll ecti on of 7,000 woody pl ants, creating one of the nation 's out­ in th e Texas Panh andl e and standing arboretum s. "''d say about 3,000 of the plants in our gar­ graduated in agronomy at Texas den came from the arboretum ," said Tony Avent, a former student of Tech Uni versity. He was legend­ Dr. Raul ston. Mr. Ave nt owns a rare pl ant nursery that was one of ary fo r hi s pl ant in vesti gati ons in the many beneficiaries of Dr. Raul ston's generosity. "Hi s mi ss ion the wild , calling himself a "pl ant was to find out what pl ants to grow and how to get th em to people." hunter" and co ll ecting seeds and cuttings that he th en devoted years Dr. Raul ston was always on the road, cri ssc rossing North Caro­ to adapting fo r use in home landscaping. Simpson felt th at it was lina, lecturing, and giving away pl ants. Three years ago he rece ived necessary to use drought-resistant native pl ants in urban Texas land­ the Thomas Roland Medal given by the Massachusetts Horticulture scapes as a method of water conse rv ati on. "It's getting to be impor­ Soc iety. He was nominated by Peter Del Tredici, the director of tant th at we save as much water as we can and grow the kind of li ving co ll ecti ons at th e Arnold Arboretum of Harvard University. pl ants th at can survive on very littl e when they have to," he said . Hi s Said Del Tred ici, "He was a selfless advocate for broadening and work at the extension center began by supervising years of futile improving th e selecti on of horti cultural pl ants and he di stributed cotton root rot studi es on th e Bl ac kl and Prairi e. Perhaps thi s spurred quite literall y milli ons of cuttings and seedlings to the nursery in­ more full y hi s interest in nati ve pl ants of th e area . He began estab­ dustry and botani c gardens." li shing field tri als for some of hi s co ll ection at the center. In the Dr. Raul ston coll ected seeds and pl ants from locations as dis­ earl y days he had to defend hi s work and the ever-growing arbore­ tant as China and as near as the North Carolina roadsides. "He would tum from being plowed under for, at th at time, Texas A&M did not bring this materi al in for trial and immedi atel y begin propagating it see the value in studying native pl ants. through his classes," Mr. Del Tredici said . "The students would bag Tim Davis, director of the center, said that Simpson was a up the cuttings and dri ve around to trade shows and nurseries. He walking encyclopedia of native plants who was "a visionary in know­ never enri ched hi s own pocket. He was like a ball of fire. He would ing how much we would come to need native plants that tolerate get hi s hands on some things and before you knew it, he would have drought and resist insects and di sease." I ,000 of them." In 1982 he helped found th e Native Plant Society of Texas. Dr. Raul ston grew up on a wheat farm in Oklahoma. He re­ He was honored in June 1996 by the Dall as Horticulture Center's ceived a bachelor's degree from Oklahoma State Uni versity in 1962 dedi cati on of the Benn y J. Simpson Native Plant Coll ecti on- 354 and a doctorate in horticulture fro m the Uni versity of Maryland in pl ants in 84 genera representing more th an 20 years of hi s research. 1966. He received dozens of honors for hi s work, including th e In th e fa ll of 1996, the Research and Ex tension Center fin all y estab­ Outstanding Public Garden Program Aw ard from the Ameri can As­ li shed the Benn y Simpson Outdoor Learning Center. Hi s book, A sociati on of Botani c Gardens and Arboreta in 1992. He was th e Field Guide to Texas Trees, was published in 1990. He coll aborated author, with Kim E. Tripp, of Th e Year in Trees: Superb Woody Plants on a number of oth er books, including Nati ve Texas Plants, Land­ for Four-Season Gardens. - Barbara A. Johnston scaping Region by Region, and How to Grow Native Plants in Texas and the Southwest with Jill Nokes. "Hi s idea was to look around you and find things of va lue instead of trying to make your land look like somewhere else," said Nokes. The famil y requests that contributions be made in hi s memory to th e Nati ve Pl ant Society of Texas, P.O. Box 891 , Georgetown , TX 78627, 51 2/238-0695. - Barbara A. Johnston

58 • HERBALGRAM No. 40 BOOK REVIEWS

erence books and ori ginal arti cles dealing excessive or long- term use; may potenti ate with various areas of safety on spec ific bo­ pharmaceutical MAO inhibi tors). Other no­ tanic als, including an earl y draft of the ti ces fo r caution and spec ific dosages are in ­ Ameri can Botani cal Co un cil 's Engli sh trans­ cluded for Ma Huang. However, Morm on latio n of the German Commission E Mono­ tea (Ephedra nevadensis) is listed as a Class graphs. I due to the fact th at thi s part icul ar variety Each herb is classified according to of ephedra contai ns li tt le or no ephedra al­ four cl asses of safety: Class I: "Herbs whi ch kaloids. The Chinese herb He Shou Wu, also Michael McGuffin can be safely consumed when used appro­ referred to in U. S. Commerce as "Fo-ti" Christopher Hobbs priately." Class 2 are herbs for whi ch the fo l­ (Polygonum multiflorum) is li sted as Cl ass Roy Upton lowing use restricti ons appl y, unless other­ 20 : Contraindicated with di arrhea; prepared Alicia Goldberg wi se directed by an expert quali fied in the root and stem may cause gastri c di stress; raw appropriate use of the herb. 2A: For exter­ root is catharti c. The common herb Purslane nal use onl y. 2B: Not to be used during preg­ (Portulaca oleracea), whi ch Jim Duke of­ Botanical Safety Handbook: Guide· nancy. 2C: Not to be used while nursing. ten recommends as an excell ent source of lines for the Safe Use and Labeling No other use restricti ons appl y, unl ess noted. essential fatty ac ids, is classed both as 2B for Herbs in Commerce by Michael 20 : Other spec ific use restri cti ons, as noted. (pregnancy) and 20 (i ndividuals wi th a hi s­ McGuffin, Christopher Hobbs, Roy Upton, Cl ass 3 herbs are those for which significant tory of kidney stones should use cautiously.) and Alicia Goldberg (eds .). 1997. CRC data ex ist to recommend the fo ll owing la­ There is also a note regarding potenti all y Press . 256 pp. Softcover. ISBN 0- belin g: "To be used onl y under the supervi­ hi gh levels of oxali c acid. 8493167 58. Price $39.95. Available from sion of an ex pert quali fie d in th e appropriate Class 3 incl udes the herb Bell adonna ABC Catalog #B27 5. use of thi s substance." The labeling must (A tropa belladonna), an herb seldom fo und This book is destined to have a sig­ in clude proper use inform ati on, dosage, in the U. S. market; it is appropri ately rel­ nifi cant impact on the labeling of thousands contraindicati ons, potential adverse effects, egated to statu s to be approved and ad min­ of herb products in the U. S. marketpl ace. drug interacti ons, etc. Finall y, Class 4 herbs istered by a quali fied hea lth professional. Secti on I 0 of the Dietary Suppl ement Health are herbs fo r whi ch "in signi ficant data is Every page of thi s book includes a and Educati on Act of 1994 (OSHEA) now ava il able fo r classification." section at the bottom of a page whi ch re­ all ows manufac turers of herbal products and For exampl e, the fo ll owing herbs are peats the defi ni tions of each of the classes phytomedicines to include dosage info rma­ classified as Class I: Bu rdock (Arctium in orde r to ensure that the reader is clear re­ ti on and, where appropriate, warnings that lappa); Cayenne (Capsicum annuum var. garding the cl assifica ti on of the particul ar guide consumers toward the proper and re­ f rutescens) with the editori al note, "The clas­ herb. Thi s fea ture has been added by the sponsible use of medi cin al pl ant prepara­ sificati ons and concern s for thi s herb are editors as a measure of responsi bility to help ti ons. Such data include contraindi cations, based upon therapeutic use and may not be the reader understand the appropri ate clas­ side effec ts, and special warnings, informa­ relevant to its consumption as a spice." -a sification. ti on not previously allowed on herbal prod­ note that accompanies a number of herbs that The book contains three appendices: ucts. The liberali zati on of thi s situati on is a are used both medicinall y an d as food fl a­ The first contains profi les on various herbal great step fo rward toward assisting consum­ vorin g: Gotu kola ( Centella asiatica); Gi n­ const ituents often considered a tox ic. e.g., ers in appropri ate and responsibl e use of ger (Zingiber officina/e); Valeri an (Valeriano cardia glycosides, oxalates, pyrrolyzidi nes, these products and reducing the possibility spp .); American Gi nseng ( Panax safrole, thuj one. Appendix 2 defi nes vari­ of adverse events. Since the safety of herbal quinquefolius). ous actions of herbs whi ch may have poten­ products is a major concern of health pro­ A signi ficant number of th e herbs tial or actual safety im pli cati ons, e.g., fess ionals, consumers, regul ators, and even li sted in thi s book have a rating in vari ous abortifac ient s, laxati ves, emetics, the herbal industry, it is important th at herbal subsets of th e category. For example, Asian emmenagogues/uterine stimulant s. gas­ products di sclose potenti al adverse effects Ginseng (Panax ginseng) is cl assed as 20 trointestinal irritants, MAO interactions, and warn certain specific groups (e.g., di a­ (contraindicated fo r hypertension). Jun iper CNS stimul ants. Appendi x 3 li sts herbs by beti cs, people with hypertension, pregnant Berry (Juniperus comunis) is classed as 2B classificati on and constitutes a cross-refer­ and lactating women) that they should avo id (contraindicated in pregnancy), as we ll as 20 ence show ing all the herbs in each of the an herb or seek professional advice, as the (not to be used exceeding 4 to 6 weeks in cl asses for easy reference. The book also case warrants. Now, for th e firs t time, a succession and contraindicated in infla mma­ has 30 pri mary references (e.g., ABC's fo rth­ group of industry-based herbali sts have re­ tory kidney di sease). The controversial herb co min g Commission E Monographs, the viewed th e 540 herbs previously published Ma Huang (Ephedra sinica) is classed as 2B British Herbal Compendium Vo lu me I, Pe­ in AHPA's Herbs of Commerce (1992) and (pregnancy), 2C (contrain dicated in nursing), ter DeS met's Adverse Effects of Herbal have prov ided safety data on th ese herbs as and 20 (contraindi cated in anorex ia, bulimi a, Drugs, Volume I and II , Leun g and Foster's guidelines for product labels. The herbs were and glaucoma; persons with thyroid imbal­ Encyclopedia of Common Ingredients Used reviewed according to an extensive li st of ref- ance should avoid use; not recommended for in Foods, Drugs, and Cosmetics, Herbal

HERBALGRAM No. 40 • 59 BOOK REVIEWS

Drugs and Phytopharmaceuticals, Hager's the intoxicating plants, and the customs as­ Hanbuch, and numerous other books on Chi­ sociated with their use, that he was to de­ nese medicine and poisonous plants. Addi­ scribe in Die narkotischen Genussmittel und ti onally, approximately 200 additional ref­ der Mensch, published in 1855. It is this erences are provided. work, the most widely known of Von Bibra's An important point about this book is prolific writings, that has been rendered into that it deals with the relative safety of herbs English under the title Plant Intoxicants. based on their common usage within recom­ Von Bibra's book was an example of mended dosage ranges and in product for­ the style of popular scientific writing of the mulations commonly found in the market­ time that included Alexander von place. The book specifically excludes and Humboldt's Cosmos, Justus von Leibig's is not relevant to data, conditions, and sub­ Chemical Letters , and Carl von Voit's Physi­ stances a) taken in excessive quantities, b) ological Letters. Published in an era when dealimg with the safety or toxicity of iso­ Plant Intoxicants-A Classic Text on the notion of experimental pharmacology lated plant constituents, c) or safety data the Use of Mind-Altering Plants by was still a novel concept even to the scien­ based on intravenous or intraperitoneal ad­ Baron Ernst von Bibra. Translated by Hedwig tifically educated, Plant Intoxicants contrib­ ministrati on, additional Chinese and Schleiffer; Foreword by Martin Haseneier; uted significantly to the rise of scientific Ayurvedic contraindications, gastrointestinal Technical Notes by Jonathan Ott. Healing materialism, and in its matter-of-fact, de­ disturbances, potential drug interactions, id­ Arts Press . 7995 . 269pp. Softcover, $ 76. 95. scriptive tone, was clearly the literary pro­ iosyncratic reactions, allergic reactions, con­ IS BN 0-89281-498-5. Available fro m ABC genitor of Lewis Lewin's Phantastica: Die tact dermatitis, and well-known toxic plants Catalog #B 191 . Betaubenden und erregenden Genussmittel: not found in the herb trade in the U.S. (e.g., The author of Plant Intoxicants, Fiir Arzte und Nichtiirzte (Phantastica: The aconite, hemlock, henbane, autumn crocus). Baron Ernst von B ibra (1806-1878), was Sedative and Stimulating Pleasure Drugs: for We commend the authors for their ini­ born into a Bavarian family of lesser nobil­ Physicians and Nonphysicians) which did not tiative and for the range and scope of their ity and modest fortune, and in many respects appear until nearly 70 years later. work. This publication surely will become his life and work typify that of the 19th-cen­ In the 17 chapters of Plant Intoxicants, a vital part of every herb and dietary supple­ tury gentleman-scientist. Von Bibra's earli­ Von Bibra summarizes and comments upon ment manufacturer's library, as well as an est years passed in the family's castle in the the current (as of 1855) state of scientific important and dispensable guide for all types village of Bibra in Northeastern Bavaria; knowledge of most of the important psycho­ of health practitioners, including phys icians, following his father's death when Ernst was active drug plants that were well-known at pharmacists, dieticians, naturopaths, herbal­ not yet two years of age, he was raised by a the time, including coffee, tea, Paraguayan ists, acupuncturists, and the like. It would family friend residing in Wiirzberg, Baron Tea (yerba mate), Guarana, chocolate, coca, also be useful for journalists, consumers, Christoph Franz von Hutton, a treasurer to opium, hashi sh, thornapple, tobacco, and regulators, and others interested in the safety the Archduke Ferdinand. As a young man, betel; the book also includes chapters on of herbal products. von Bibra studied law, chemistry, and medi­ some psychoactive intoxicants rel atively As the herb market continues to mush­ cine at the University of Wiirzberg. At the obscure at the time, and that remain more or room at unprecedented rates in the U. S. and age of 18, he inherited the family estate at less obscure today. Thus, there are chapters many other pl aces worldwide, additional Schwebheim, and the income from this ru­ on coffee leaves as a beverage, Fahan Tea authoritative information becomes increas­ ral property afforded him sufficient means (the orchid Angraecum fragrans Thouars), ingly valuable regarding the appropriate safe to pursue a life as a scholar, traveler, inde­ Khat, Fly Agaric (Amanita muscaria), the and responsible use of many of these prod­ pendently funded scientist, and man of let­ opiate derived from the "poison lettuce," ucts. Any guidance that can reduce the ters. Von Bibra published works on art his­ Lactuca virosa L., and arsenous acid or ar­ chances of a person misusi ng or abusing an tory, forensic chemistry, and forensic medi­ senic trioxide (As )- the latter was cus­ 20 3 herbal product is welcome and timely. This cine and achieved recognition and awards for tomarily consumed in minute amounts by book makes a significant contribution to the hi s contributions from various scientific some Victorian girls at the time as a sort of herbal literature at the close of this century academies; however, he became most famjJ­ cosmetic tonic; it gave a rosy glow to the and will no doubt become a seminal and of­ iar to a wider audience for hi s travelogues, skin due to capillary damage and transduc­ ten cited work well into the next. -Mark novels, ethnographies, and works in natural tion of hemoglobin into the skin . Little in­ Blumenthal and cultural hi story, produced following a formation was available on some of these year-and-a-half sojourn in South America. It materials at the time, and the brevity of the was there that he first encountered many of chapters on these topics in Plant Intoxicants

60 • HERBALGRAM No. 40 BOOK REVIEWS

reflects this paucity of knowledge. Von Bibra such, Plant Intoxicants belongs on the book­ devotes a few pages to each of these intoxi­ shelf of any scholar with an interest in the cants, reporting on their botani cal origins, scientific, cultural, ethnographic, and histori­ their customary manner of usage, and com­ cal aspects of psychoacti ve drug plants. - ments on the effects of the preparati ons and Dennis McKenna, Ph.D. their chemical composition; although in many cases, he is led into speculati on on that topic since the acti ve constituents, even of relati vely well-known drug plants such as coca, had not been thoroughl y in vesti gated. (Cocaine, for example, was not isolated and definiti vely characteri zed until 1860, five "XOCHI SPEAKS" POSTER years after the publicati on of Von Bibra's AND BOOKLET ity at once, hinting at the panascopic experi­ book). In this respect, the Technical Notes "Xochi Speaks" is a bold introduction ence that psychi c "travelers" descri be. For provided by Jonathan Ott are a useful adden­ to the benefits and hazards of psychoactive anyone contemplating inner space travel , dum to the main text, for they provide the substances of both plant and synthetic ori­ Xochi pi lli is a competent silent gui de. In reader with a summary of the scientific gin . The 24- x 36-inch full color poster by our culture where excesses have taken a dev­ knowledge regarding these plants that has LordNose! depicts Xochipilli, Aztec prince astating social toll , Xochipilli 's teaching re­ accumulated in the 140 years since Plant of fl owers, seated in eternal "stoned" bliss, fl ecting the ancient wisdom of traditi onal Intoxicants was first published. his gaze directed upwards towards internall y culture, as well as the modern tenet of phar­ In other instances, however, items dis­ generated wondrous images. LordNose! pro­ macology- that dosage counts-is conveyed cussed in the book, particul arl y opium, cof­ vides us with a glimpse of the revealed mys­ in an inspired, aestheti c, and unequivocal fee and tea, hashi sh, chocolate, and tobacco, teries-Xochipilli here looks upon his "flow­ format. were already in widespread use around the ers," an arc or rainbow of mul ticolored mol­ "Xochi Speaks" has been thoroughly world, were fami li ar to many Europeans, and ecul es. The message, that chemistry mat­ researched and referenced. The artist, Marc were economicall y important agri cultural ters, seems clear. The artist, not intimidated Franklin, has assembled an impressive array commodities. A considerable body of prac­ by chemistry, represents the molecul es that of expert consultants, coll ecti vely known as tical and scientific kn owledge regarding the supply these visions with three-dimensional LordNose! Dr. David Nichols and Dr. Rob­ botani cal origins, varieties, commercial pro­ clarity. In fact, the molecul es (appropriately) ert Pfaff created the computer-generated ducti on, customary methods of use, nutri­ have more substance and corporeality than three-di mensional molecular structures. tional compositi on, pharmacological effects, th e god, who appears from afar to be made Douglas Trainor and John Labovitz are the and chemi cal properti es of these more "main­ of stone but on closer inspecti on is di sinte­ computer specialists who assisted the artist stream" psychoacti ve plants was already ex­ grating into pi xels of cyberspace, suggestive in reali zing hi s vision. The entire project was tant at the time Von Bibra wrote, and he was of the "surreality" and evanescence of psy­ proofread by Dr. Alexander Shulgin . Other careful to summarize this corpus of knowl­ chi c experience. Xochipilli, the Aztec god contri butors wish to remain anonymous. The edge in each of the relevant chapters. Much intent upon the molecul es, attests visuall y to poster contai ns "at-a-glance" ethnobotanical, of thi s materi al is still info rmati ve fo r many th e sacred nature of ritual uses of psychoac­ pharmacological, and chemical information, contemporary readers, with the exception of ti ve subtances in traditional societi es. These including dosage, anti cipated reactions, ad­ those who have already conducted an in­ molecul es are to be treated with great rever­ verse reacti ons, and contraind ications that are depth study of the varietal forms, post-har­ ence and respect and are not to be taken easil y explained for the layperson. Sugges­ vest processing, and cultural and economic li ghtl y. ti ons for maximizing one's psychoacti ve ex­ hi stories of these important commercial Psychoacti ves may not be the onl y way perience are included. The poster is accom­ drugs. to arrive at a deeper understanding and fee l­ panied by a sixteen-page bookl et, A Guide In summary, Von Bibra's book is a ing of connectedness with the inner and outer to the Psychedelics, that gently in troduces cl assic of the genre, and at the time of its cosmos, but they are a conveni ent and quick, the molecul ar structu re of psychoactive sub­ publication was a valued compendium of though potenti all y toxic, way to get there. stances, li sts further readings, and contains knowledge for scientific professionals and Against a dark blu e background of deep info rmati on on nu tritional support, metabo­ educated laymen alike. It was a seminal work space and a pervasive cloud -like atmosphere, lism, and cross tolerances. The attractive in many respects, the forerunner of later clas­ the fo ur miniature images of Xochipilli that poster graces Dr. Richard Evans Schultes's sics in the fi eld of ethnopsychopharmacog­ fl ank the central figure show the vari ous per­ home and my own. "Xochi Speaks" is avail ­ nosy that achi eved far wider recognition. As specti ves of Xochipilli's multidimensional- able fo r $20 post paid, domestic; $25 fo r-

HERBALGRAM No. 40 • 61 BOOK REVIEWS

eign from LordNose! Box G473, San Fran­ sourcebook. I feared this new book would for infants, chewed upon to alleviate teeth­ cisco CA 94117. - Janna Weiss, M.S. be largely a bibliographic echo of that clas­ ing problems. Under Other Medicinal Us­ The reviewer is an acupuncturist and sic. But no!!! Even the cover tells me that age, the glumes [chaffy basal bracts on the herbalist currently working on a Ph.D. in one-third of the species treated were not in­ spikelet of a grass] are used for medical ethnobotany, Department ofBotan y, cluded in WBB. I was pleasantly surprised cholecocystosis and nephrosis in China and University of Texas at Austin. when I dug in for an evening to peruse this Japan, and for bronchitis, cystitis, and ure­ new classic. This fact-full book reports Zulu thritis in Europe. Roots are used for gonor­ uses on more than I ,000 species, roughly 25 rhea in the Phi Ii ppi nes, for dysmenorrhea on percent of the flora of KwaZuliu-Natal, South the Indian Peninsula, and for worms in Ma­ Africa. laysia. Plants are used as diuretics in Viet­ There's a lot of good new data. For nam, the stem juice used to alleviate irrita­ example, I was pleased to find that the book tion from wounds in Liberia. In Mauritius, had more on the chemistry of Pygeum the fruit decoctions are gargled for sore africanum (with updated nomenclature to throats and taken for dysentery and urethri­ Prunus africana), now being promoted for tis . Roots of the Chinese variety ma-yuen benign prostatic hyperplasia (BPH), than I are used for neuralgia and rheumatism. Un­ had in my files. I was not excited by the der Physiological Effects, we learn that the non-quantified comment "The wood, flow­ glume decoction or tincture is reputedly cool­ ers and fruits all contain sterols." I suspect ing, depurative and diuretic, the root anthel­ that's true of all living plants. As early as minthic. Under Chemical Constituents and 1970, the sterols were found in patent medi­ Biological Properties, there's a long listing cines for treating BPH. And in 1986, bark of chemicals, many the ubiquitous amino and was used in patented hair tonics. But the only fatty acids that occur in all living species. I Zulu medicinal uses reported were for witch­ was pleasantly surprised to find that the ac­ craft and intercostal pain, neither reported in count added nearly a dozen compounds to Zulu Medicinal Plants: An Inventory. the earlier classic. Four Zulu names are my Father Nature's Farmacy (FNF) Data­ A. Hutchings, A H. Scott, G. Lewis, and given, that make the Latin look elementary: base. A Cunningham. 1996. University of Natal lnyazangoma-elimnyama, umdemezulu, We also find bioactivities, e.g., the Press. 450pp. $114. 95 paper; ISBN # 0- undumzula and umkhakhazi. There's an antiinflammatory, antitumor, CNS-depres­ 86180-8931. Available from ABC Cata­ equal array of Afrikaans, Dutch, and English sant, and immunomodulatory activities, re­ log #B247. names: bitter almond, bitteramandelboom, ported for coixenolide. "Germanium com­ Packing for my first African Rainfor­ nuweamandelhout, red stinkwood, and pounds from the seeds have been found use­ est Pharmacy ecotour, I was more than rooistinkhout. ful in the treatment of muscular pain and ar­ pleased to accept an invitation to review this Taking a look at just one of the grass thritis (Sugmito, 1987). Two benzoxcanoid rather expensive book. Having just given a species, the Job's tear (Coix lacryma-jobi L.), compounds from the roots have anti-inflam­ talk on what I call the millennia) medicines whose seeds, drilled and strung on strings, matory properties and inhibit histamine re­ (empirical folk medicines) and the centen­ are all too frequently brought back to the lease." Under Notes, we read that the seeds nial (synthetic) medicines, I treasure the fron­ USA illegally by tourists (since grass seeds of this exotic plant are ground and made into tispiece quote from the late Dr. M.Y. may harbor viruses, it is technically illegal beer or flour. Concisely, under Selected Fur­ Gumede, medical practitioner: to bring them in without going through the ther Reading Abstract Numbers we find per­ "What is little appreciated is that there permitting process). For the Job's tear entry tinent abstract citations. is no conflict between the two systems, viz. on p.l7, there's a code number, K20, which I dare say that going through the book the old and the new (my millennia) and cen­ will be wasted on most of us. It's a coding systematically, as I hope to do someday, will tennial) or the traditional and modern sys­ telling us where the species is placed phylo­ add more than 2,000 chemical activities and tem of medicine. The two apparently con­ genetically in the herbarium. Then there's I ,000 biological activities to my FNF data­ tradictory systems are only complementary. the scientific name and the usual generic and base. This Zulu book turns out to be an in­ Where one fails, the other takes over. Each specific names, with the authority of this spe­ teresting source also for English common needs to understand the working of the other cies. Then there are common names in En­ names I haven 't found elsewhere, not to one." (Gumede, 1990). glish and South African, Job' s tears, mention the fabulous repository of local Zulu For years I have treasured my classi­ Jobskrale, tandkrale, transgras, then the uses, beverages, dyes, food , medicine, and cal Watt and Breyer-Brandwijk Poisonous Zulu name ilozisi. witchcraft. Thus I can heartily recommend and Medicinal Plants of Southern and East­ Under Zulu Medicinal Usage, we learn it to fact-finders and readers interested in ern Africa ( 1932) [WBB] as a very useful that the seeds are worn as good luck charms anthropology, botany, conservation, medi­ cine, and phytochemistry. -Jim Duke 62 • HER BALGRAM No_ 40 BOOK REVIEWS

food, shelter, and medicine. Westerners these detailed monographs opens with use who have collected information have only from the Maori tradition, combinmg myths, gathered a mere fraction of the rituals, origins, history, sayings, and practical uses. practices, and healing methods of the Many monographs contain a subsection, individual native groups. Collecting data " relationships," which describes how from manuscript and literature sources, the related species are used in other cultures. author has compiled the most extensive External and internal uses are enumerated treatise on the use of New Zealand's flora in separate sections. These sections are a by its native groups. The book is divided chronology of the travel, nature, botanical, into two parts. Part one details Maori and historical literature on New Zealand, healing and health topics, with an consisting largely of direct quotes from the alphabetical listing of 86 topics from cited works. Complementing each Maori Healing and Herbal. Murdock abortion to yeast infections, with notations monograph are color photographs by Brian Riley, Photographs by Brian Enting. Viking on how the condition was perceived and Enting, representing as fine a photographic 5evenseas N.Z. Ltd. 1994. 528 pp. Hard­ treated by the Maori as viewed from feast as there is to be found in any medicinal cover. $65. 15B50-85467-095-5. Available historical reports by Westerners, with plant book. from ABC Catalog #B222. occasional ethnobotanical observations. Maori Healing and Herbal is limited Physically isolated in the vast ocean Cultural context is sometimes diluted by to one geographical location. However, this expanse of the South Pacific, New Zealand the ethnocentric prejudices of the early herbal is a world-class, exceptiona I is an island paradise in the truest sense, observers. However, the author has contribution to ethnobotanical literature, offering everything from hauntingly attempted wherever possible to supply the and will be a welcome addition to any beautiful black sand beaches to subtropical view of the Maori, intertwining rich herbal library.- Steven Foster rainforests to alpine meadows in the young knowledge of medicinal plants with snow-capped peaks of the South Island. If NOTICE: Due to its technical nature, the spiritual and practical applications. one had the opportunity to choose a climate publication of the English translation of the Part Two, Maori Herbal Remedies, is and location perfect in all its diversity for German Commission E Monographs has been an encyclopedia on 200 important delayed. We expect to ship all prepublication human habitation, you would be medicinal plants of the Maori, arranged orders for the book by the end of September. hard-pressed to make a better choice than alphabetically by Maori names. Each of We greatly appreciate your understanding the New Zealand archipelago. From a and patience.-ABC staff botanical standpoint, New Zealand is rich. There are at least 4,162 vascular plant species in the New Zealand flora of which ToP I 0 SELLERS FROM THE nearly 2,284 species (54.9 percent) are native. Of the native species, I ,524 (66. 7 ABC CATALOG percent) are endemic. Much of New January through April I 997 Zealand's present vegetation is dominated Previous standing shown in () by an additional l ,878 species of adventive vascular plants introduced to the islands by I. German Commission E Monographs: Blumenthal, Gruenwald, Hall , Riggins, and Rister eds., humans. Early explorers were interested Klein & Rister (t rans) (in press) ( I) in native timber such as the enormous 2. Herbal Prescriptions for Better Health: Brown (new listing) evergreen kauri trees (Agathis australis 3. Herbs of Choice:Tyler (3) Sted., Hort. x Lindley, Araucariaceae), the 4. Herbal Prescriber Database: Hobbs (new listi ng) gum of which has been used as an 5. Cancer and Natural Medicine: Boik (5) antiseptic. 6. Herbal Medicine:Weiss (6) 7. Herbal Medicines: A Guide for Health-Care Professionals: Newall, Anderson, and Ph illipson From the time that Sir Joseph Banks (new listing) first stepped ashore during Captain Cook's 8. Encyclopedia of Herbs and Their Uses: Bown (2) first visit to New Zealand 1769-70, 9. Encyclopedia of Herbal Medicine: Bertram (new listing) Westerners have been recording uses of I 0. Cat's Claw: Healing Vine of Peru: jones (new listing) plants. The indigenous groups of New Zealand, known collectively as the Maori, See ABC's Herbal Education Catalog in the center of th is issue for th ese and over 200 relied on the flora for hundreds of years for books on herbs and phytomedici nes, or call 800/ 373-7105 for more information.

HERBALGRAM No_ 40 • 63 LETTERS ,_--...,. ...-.. -. __.,., ...... --- -l ~ ~ ~ ~ WHAT'S IN A NAME? neric name-even though the discoverer I would like to offer a suggestion. If Monroe Wall considers that an ugly sound­ you do not already publish literature under ing name. I think we should give BMS the the name, "Journal of the American Botani­ "weenie of the week" award, but I hear that cal Council," you might consider giving that that phrase may be trademarked too. title to your HerbalGram publication. I sug­ Madeleine conceded that BMS owns the gest this because many of the libraries and trademark on the drug, even though Monroe medical personnel I asked about locating named it taxol in 1967, 25 years before BMS copies commented that it wasn't a "signifi­ ~ got the trademark on Taxol ( 1992). cant enough" publication for placement in JYrOCI\ABJ.fJA As editor of Chemical & Engineering general or medical libraries. If it truly con­ l! ___ _..------~ News, she asks on the editorial page, "What's tains authoritative material by specialists in Crataegus monogyna in a Name?" the area of botanical medicinals, etc., this title "Take, for example, the case of the an­ might help convey that aspect to a broader ticancer compound originally isolated from readership. the Pacific yew tree. I'm not allowed to use B. Mishkin the name without capitalizing it, but you Skokie, Illinois TRADEMARK TIRADE know what I mean. (T)hat universall y fa­ The title isn't what lends significance At my old USDA office in Beltsville miliar name is now off limits." to a periodical; it's the content. HerbalGram is a dusty old file from the sixties, when Bob Maureen Rouhi (1996) adds that Mon­ is a magazine, not a scientific journal, though Perdue and Art Barclay were arranging for roe Wall was "basically surprised but not it is a magazine with scientific information, collections of yew for the National Cancer resentful , and, to some extent, amused" that such as Current Science. A scientific jour­ Institute in the so-called NCI/USDA Cancer the name taxol which he had created "could nal is a periodical in which original research Screening Program, a program which lasted indeed be trademarked." I've used the term is reported. A few review journals summa­ until 1982. Yes, even the USDA was in­ Herbal Vineyard for my farmette and have rize ori ginal research as well. HerbalGram volved in this tedious 30-year process of incorporated the name as Duke's Herbal isn't and shouldn't attempt to be a journal. moving taxol from the yew to the pharmacy. Vineyard, but that does not keep someone Many scientific libraries subscribe to maga­ Taxol was finally approved for ovarian can­ from trademarking the name. I have also zines which they consider relevant to their cer in December of 1992. And today, I'm referred to my database as Father Nature's interests. Unfortunately, there really isn't a told, it may be illegal for me to even use the Farmacy, but it sounds as though anyone scientific journal specializing in the content name taxol which Monroe Wall applied to could trademark that and take it away from of HerbalGram. the drug he discovered. (I suppose it's legal me, unless I trademark it myself. John Buetler, Ph.D. as I stress that by taxol , I am talking phy­ James A. Duke, Ph.D. Natural Products Chemist tochemical history and I mean the compound Herbal Vineyards National Cancer Institute that Monroe Wall found and named, and not Fulton, Maryland the trademarked name that Bristol-Myers KUDO Squibb (BMS) co-opted for their anticancer I've been a longtime subscriber to drug.) U.S. FUNDRAISER REQUESTED HerbalGram (since its beginnings actually, A great deal of effort was put into this The Foundation for the Preservation and have a complete set of the earliest is­ di scovery by the USDA, much more by the of Tibetan Medicine is seeking a U.S. sues!) and can't believe how much the maga­ NIH and their contractors but as far as I know, fundraising coordinator to work in conjunc­ zi ne has grown. It seems hardly possible, none of the profits go to the USDA; maybe tion with the foundation's directors to de­ but each issue seems to get better. The ar­ some go to NIH; most profits go to BMS who velop and implement fundraising programs. ticles are terrific, the artwork superior, the now tell us that the original name taxol Current projects include the establishment of layout and design, etc., etc., etc. Thanks a "should only be used to refer to the antican­ two traditional Tibetan medical schools and lot for a quality publication. I am one among cer preparation sold by Bristol-Myers Squibb a medicinal herb garden-project sites are many who deeply appreciate the quality of Co.," according to the attorney Madeleine in some of the most breathtaking areas of work you are doing. Jacobs (C & EN 1996) quotes. Nepal and Ladakh, India. Rosemary Gladstar "Chemists, and C&EN, are coming Tibetan Medicine is a 2,300-year-old East Barre, Vermont around to using paclitaxel, the approved ge- comprehensive medical system that seamless I y blends science and spirituality. MOVING? It is also called "Amchi Medicine" from the Our mail permit does not allow us to forward HerbaiGram. If you move or change your mailing Mongolian word for doctor. address, please notify us immediately so you will not miss any copies. Send your change of address notice to Margaret Wright, Circulation Manager, American Botanical Council, P.O . Box 201660, Austin, TX 78720-1660. 512/33 1-8868, Fax: 512/33 1-1924.

64 • HERBALGRAM No. 40 LETTERS

ABC NEWS In many remote villages the amchi or NEBRASKA VS. MA HUANG traditional doctor is the only medical practi­ continued from page 8 tioner providing treatment free of charge to I hope you will be able to answer or University of Houston College of Phar­ fellow villagers. These traditional doctors print all or any part of the following: macy Continuing Education Program, Hous­ live in remote high-altitude areas close to the In regard to the HerbalCram No. 38 ton, Texas, "Herbal Medicine, Homeopathy and medicinal plants. Amchis learn about the [page 31] letter on Nebraska criminalizing Phytomedicinals: Phytomedicines, Regulatory plants in a direct, experimental way, gaining Ma huang, please clarify the issue in regard Agencies and Reform in the United States" knowledge not available through books. A to non-residents who may be traveling University of Texas Contemporary Is­ master herbalist will traditionally mentor a through the state. It mentions possible felony sues Course, Department of Pharmacy Prac­ young amchi in the use of plants for healing. prosecution for "possession." Does this tice and Administration, Austin, Texas, "Phy­ The mentorship usually lasts over twenty mean if one legally purchases the herb or tomedicine" Lecture Western States Chiropractic College, years. Many of the practitioners are in their even ephedrine in another state and is stopped Botanical Medicine Program, Portland, Oregon, late fifties and early sixties and, except in with it in the car while passing through the "The German Commission E Monographs: A rare cases, they have no students. In the next state [Nebraska], one is committing a felony? Model for Regulatory Reform?" five to ten years these practitioners will ei­ Since this appears to be the case, interstate Continuing Education Program for ther become too old to teach or will simply travel is prohibited. Therefore, as an officer Chiropractors and Pharmacists; Austin Di­ pass away. With them a reservoir of ancient and director of many professional societies etetic Association, St. David's Hospital, Aus­ knowledge will vanish. and social clubs, I will make sure we do not tin, Texas" An Overview of Herbal Medicines in We have an opportunity to create hold any seminars/meetings in Nebraska. U.S. Selfcare and Healthcare schools for this knowledge to be passed from What happened to our constitutional ri ght to National Nutritional Foods Association­ the old to the young. These students will interstate travel? Please address thi s issue. North West Featured Speaker, Seattle, Wash­ ington, "Perspectives on Evaluation and Regula­ become the teachers of the next generation Dan La Valley ti on of Herbal Medicines" ensuring that this ancient healing tradition Ruskin, Florida Bastyr University Class Presentation, does not disappear. [Ed note: According to attorney An­ Bothell, Washington, " Perspectives on Evaluation The foundation has been created with thony Youn g of Piper & Marbury, "Nebraska and Regulation of Herbal Medicines" the support of prominent traditional doctors apparently treats Ephedra as a controlled New Jersey Dietetic Association Meet­ who have been working independently to substance. Possession of a controlled sub­ ing, Rutgers Cooperative Extension, sustain and renew traditional Tibetan medi­ stance is unlawful. You can travel in Ne­ Flemington, NJ , "Assessing the Safety and Effi­ cine in remote areas. They realized Tibetan braska, but not with Ephedra. There is no cacy of Herbs & Phytomedicines: The German medicine is at a critical juncture in its trans­ prohibition on travel in Nebraska-just on Commission E Monograph System: A Model for mission and no individual working alone can possession of Ephedra. [This is} no different Regulatory Reform for Herbs and Phytomedicines in the U.S. ?" ensure its survi val. than the fact that your right to possess can­ Rutgers University, New Brunswick, For over two decades these doctors nabis (marijuana) in California gives you no ew Jersey, "Standardization of Nutraceuticals" have been working with very limited re­ right to possess it in a state where possession is Alternative Therapies Conference, "Ex­ sources. Each is confident the communities a crime." ploring the Forces of Healing," Orlando, Florida, they work with will support a traditional In a letter to Dr. Mark Horton, Depart­ "Plants that Heal: A Review of the Therapeutic practitioner. ment of Health, Nebraska, Senator Kermit Aspect of Leading Herbal Medicines as Approved However, neither the doctors nor the Brashear, author of LB 1232, "written to in­ by the German Commission E" communities have the resources necessary clude all products that contain ephedrine Conference for Health Professionals, to create the schools, hospices, and medici­ with a few exceptions," said, "as the law has "Scientific Validation of Natural Medicine," nal plant cultivation sites needed to train a taken effect, I have been informed that some Green Bay, Wisconsin, "The Rational Use of new generation of practitioners. products that contain small amounts ofephe ­ Herbal Therapies" Pharmacist's Continuing Education, Applicants should have fundraising drine may not be subject to abuse. It is un­ Sponsored by Pharmavite, Nashville, Tennessee; experience and be willing to work hard at a fortunate that such dialogue did not take Drugs, Chemicals and Allied Trades Associa­ difficult task. Applicants should send a cover place during the legislative process .... "] tion Vitamin & Nutritional Supplements Semi­ letter and resume to: Joseph Chinnock, GPO KUDO nar, New York, New York, "The Herbal Supple­ Box 5741, PCN 243, Thamel, Kathmandu, I want to congratulate you on your fine ments Industry: Both Sides of the Atlantic" Nepal. Phone/fax 977-1-428-578. Mem­ 1997 PhytoPharmica Conference for publication, HerbalGram. I recently re­ bership information: The Foundation for the Health Professionals, " Rational Use of Herbal ceived my first copy earlier this month after Preservation of Tibetan Medicine, 30628 Therapies," Chicago, Illinois; Philadelphia, Penn­ attending the Botanical Medicine certifica­ Detroit Rd., #300, Westlake, Ohio 44145. sylvania; and Atlanta, Georgia tion program sponsored by Western States Email: joseph @frontier. wlink.com.np. Chiropractic College. I'm looking forward Jos. Chinnock to future issues. Thanks for the additional enlightenment and for opening my door a little wider. Michael McCullough, D.C. HERBALGRAM No. 40 • 65 ACCESS

In this department of Herba/Gram, we li st resources such as publications, organizations, seminars, and networking for our readers. A listing in this section does not constitute any endorsement or approval by Herba/Gram, ABC , HRF, or the HRF Professional Advisory Board.

A World of Plants Discovery Series at the Enid dealing with research, management, policy mak­ Review ofAromatic and Medicinal Plants, an ab­ A. Haupt Conservatory Series, New York Botani­ ing, and conservation. Key journals and databases stract journal covering the literature on cultivated cal Garden. Tropical Lowland Rain Forest, Au­ in the field are highlighted. $12. Contact: Ameri­ and wild species of culinary herbs and spices and gust 2-3 ; Aquatic Plants, September 6-7; Tropi­ can Botanical Council, 512/331-8868. Fax: 512/ essential oil , medicinal, and pesticidal pl ants, cal Upland Rain Forest, October 4-5 ; Deserts of 331-1924. Emai l [email protected]. available from CAB International. Topics include the Americas, November 1-2; and Deserts of Af­ Catalog #B-253 . biodiversity, ethnobotany, botany, horticulture, rica, December 6-7. Conservatory Exhibition : economics, phytochemistry, biotechnology, phar­ The Tropical Rain Forest and Medicinal Plants Journal Watch, published semimonthly by the macognosy, herbal drugs, perfumes, cosmetics, through November 19. New York Botanical Gar­ Massachusetts Medical Society, 1440 Main Street, botanical pesticides, pharmacology, toxicology, den, Bronx, NY, I0458-5126. Ph: 718/817-8616. Waltham, MA 02154-1600. Subscription price and more. Also available on floppy disk. For Fax: 718/562-8474. $89/year, student rate $55. Ph: 800/843-6356. information, contact CAB International, 198 Fax: 617/893-0413. Madison Avenue, New York, NY 10016-4314. Bed and Breakfast for Garden Lovers, a guide Ph: 2121726-6490. Fax: 212/686-7993. to properties offering accommodations where Medicinal Plant Conservation Bibliography, Vol­ guests and hosts share a common love of gardens ume 1, compiled by Dr. Uwe Schippman. In­ Robyn's Recommended Reading, a quarterly re­ and gardening. The 1997 edition features 82 cludes 774 references published in monographs, view of literature relating to herbalism and members in England, Scotland, Wales, and north­ journals, serial publications, and grey literature, phytotherapy, edited by herbalist Robyn Klein. ern France. Homes vary from cottages and farm­ primarily from 1990-1996. Short reviews of 71 Stay on top of important information concerning houses to rectories and manors. Includes infor­ 1996 papers. References indexed by general, geo­ herbalism and the use of plants for health and mation on residential garden courses, tours of pri­ graphic, and taxonomic keywords. $12. Con­ healing. Subscriptions $1 5/yr. Publi shed quar­ vate homes, and some places to stay in other parts tact: American Botanical Council, 512/331-8868. terly by Sweetgrass Herbs, Inc., 1627 W. Main, of the world. Send three international reply-paid Fax: 512/331-1924. Email: Ste. 116, Bozeman, MT 59715. coupons with a self-addressed envelope to: custserv @herbalgram.org. Catalog# B-254. BBGL, Handywater Farm, Sibford Gower, The Thomas Jefferson Center for Historic Banbury, Oxfordshire OX I 5 5AE, England. Fax : "Return to the Amazon," Margaret Mee Exhibi­ Plants, established at Monticello in 1987, collects, 44 1295 780990. tion at the Museum of Natural Science, Houston, preserves, and distributes historic plant varieties TX, through September 21 , 1997. One of the fore­ and strives to promote greater appreciation for the Directory for Medicinal Plants Conservation, most botanical artists of all time, Margaret Mee's origins of garden plants. Jefferson 's horticu ltural jointly published by the German Federal Agency paintings of Amazon plants have done much to interests are highlighted, along with varieties for Nature Conservation and the IUCN/SSC Me­ alert public attention to the need for conservation documented up to the early twentieth century and dicinal Plants Specialist Group. Providing infor­ of the Amazon Forest. The exhibition includes choice North American plants. For a copy of mation for policy makers, scientists, and techni­ her paintings, sketch books, a reconstruction of Twinleaf, the annual newsletter, send $1 to Tho­ cal experts in the management of medicinal plant one of her "fie ld base huts," and three video mas Jefferson Center for Historic Plants, resources. Information on more than 200 net­ screens with Margaret talking about aspects of her Monticello, P.O. Box 316, Charlottesville, VA works, organizations, and projects world wide art and conservation beliefs. 22902. Ph: 804/984-9822. Fax: 804/977-6 140.

CALENDAR

July 10-13: Herbs '97: International Herb and levels of experience. Herbal educators in­ july 26-30: 38th Annual Meeting ofthe Ameri­ Association's 12th Annual Conference, Danvers, clude authors Rosemary Gladstar, Colleen K. can Society of Pharmacognosy, University of MA. Hands-on workshops and demonstrations Dodt, and Dorie Byers. Contact Herb Gatherings Iowa. "Diversity in Natural Products Chemistry: cover a wide range of topics designed to meet the 2000, I0949 East 200 South, Lafayette, IN 4 7905- Sources and Applications" and "B iocatalys is and professional needs of the herb business owner. 9453. Ph:. 317/296-4 116. Biosynthesis of Natural Products" are the primary Network, meet new sources, get new ideas and themes. Three symposia with 10 outstanding sci­ marketing tips. Speakers include Linda Ligon and july 22-23: The Health Benefits of Natural entists, and a large number of oral presentations Mark Blumenthal. Contact: IHA, 847/949-4372. Phytoceuticals: Examining the Health Benefits and posters sessions. Contact Ms. Jo Dickens, and Pharmaceutical Properties of Natural An­ Iowa Memorial Union, University of Iowa, Iowa July 11 : Herbs, Exercise, and Change: Alter­ tioxidants and Phytochemicals, Montreal, Que­ City, lA 52242. Ph: 319/335-3231. Fax: 3 19/ ing the Faces ofAging, Con dell Medical Center, bec, Canada. Join the leaders in the field as they 335-3533. Email: [email protected]. Libertyville, IL. The mission of this conference share the botany, chemistry, and pharmacologi­ is to empower change with aging. Keynote lec­ cal properties of the phytoceuticals that exhibit August 1-3: Cultivation and Preservation of ture "Herbs for Health" by Mark Blumenthal. the most promise for a healthier lifestyle. Topics Medicinal Plants, Sage Mountain Retreat Cen­ Contact: Craig Dean, M.D., 719 Stonegate Ct., include health conditions to prevent and control, ter, East Barre, VT, hosted by the United Plant Libertyville IL 60048. Ph: 847/362-2900. antioxidants and phytochemicals in foods and bo­ Savers. Join Rosemary Gladstar, Kate Gilday, tanicals, and the future of phytoceuticals. Con­ Don Babineau, Paul Neidhart, Mark Cohen, and july 19: 1st National Herb Gatherings 2000 tact International Business Conferences at 508/ Andrea and Matthias Reisen on this 500-acre na­ Conference, West Lafayette, IN. A day of fun 481-6400. Fax: 508/481-7911. Email: tive plant preserve and herbal retreat center for a and education for herb enthusiasts of all interests inq @ibcusa.com, Website: http:// weekend of workshops, planting projects, and www.ibcusa.com/conf/phytoceuticals. other herbal activities. Contact United Plant Sav-

66 • HERBALGRAMNo . 40 CALENDAR

ers, Box 420, East Barre, VT 05649. Ph : 802/ Rosemary Gl adstar, and many more. Sage Moun­ Carolyn DeMarco, M.D. , Jan de Vries. Ph .D. , Alan 4 79-9825. Fax: 802/4 76-3722. Emai I: tain Herbs, P.O. Box 420, E. Barre, VT 05649. R. Gaby, M.D., and Michael Janson, M.D. Con­ [email protected]. Ph : 802/479-9825. tinuing Education Credits offered by Bastyr Uni­ versity. Contact Shelly Petska at IMPAKT Com­ August 3: Natural Business Financial & In­ August 24-27: Bioassay Methods in Natural munications. P.O. Box 12496. Green Bay, WI vestment Symposium, at the Organi c Farming Product Research, Uppsala, Sweden. The latest 54307-2496, 800/477-2995. Fax: 414/499-3441. Research Fou ndati on's Third "Organic" Business developments in methods fo r the screening of and Regu latory Leadership Conference, Oak land, plants fo r biologicall y act ive substances and new September 26-28: Green Nations Gathering, CA. The symposium features se minars, breakout discoveries. Ph ytochemical Society of Europe. wi th special guest, Dr. Rosi ta Arvigo. This long sessions, and Q & A opportunities for marketers Contact: Professor L. Bohlin, Di vis ion of Phar­ weekend includes an herbal emporium, sweat and investors in organic food s, natural products, macognosy, Biomedic al Centre, Uppsala Univer­ lodges, and workshops by several lead ing herb­ herbal medicines, and dietary supplements. Con­ sity, P.O. Box 579, S-751 23 Uppsala, Sweden. ali sts inc luding Dav id Hoffmann , Susun Weed, tact: OFRF, P.O. Box 440, Santa Cruz, CA 9506 1. Ph:461 8 174492. Fax:46185091 0 1. Email : Amanda McQuade Crawford, Ryan Drum , Doug Ph : 408/426-6606. Fax: 408/426-6670. Ema il: Lars.Bohlin @pharm acog. uu .sc. Elli ott. Dav id Winston, Chri stopher Hobbs, Ed research @ofrf.org. Smith, James Green, Janice Longboat. Eli ot September 5-7: 14th Annual Breitenbush Hot Cowan, Gail Ulri ch, Kate Gilday. Dr. Michael August 3-5: The International Mint Symposium, Springs Herbal Conference, Detroit, Oregon. Tierra, and others. Nestled hi gh in the Catskill at the Westin Hotel in Seattle, WA. Dealin g wit h Three days of herbal workshops taught by some Mountains of New York at the beautiful Phoenicia all aspects of mint production, thi s sy mposium of the finest herbalists in the country in a settin g Pathwork Center. Come together to learn, net­ brings together processors, traders, dealers, buy­ of green forests, wild ri vers, and healing mineral work , play. and honor the earth. Contact Pam ers, and users of peppermint and spearmint prod­ hot sprin gs . Teachers include Amanda McQuade Montgomery. P.O. Box 266. Milton. Y 12547. ucts from all over the world . Topics include grow­ Crawford, Ryan Drum, Cascade Anderson Geller, Ph : 9141795-5238. ing, processin g, analysis, use of mint oil s in con­ James Green, Ed Smith, Kathi Kev ill e. and Mark sumer products, trade stati sti cs, and the latest sci­ Blumenthal. Over 40 workshops for all levels of September 27: Chinese Herbology, Connecticut entific research and commercial production tech­ interest and expertise. Contact Autumn Summers In stitute for Herbal Studies. A five month, one nology. Tour mint farms and distilleries in Wash­ at P.O. Box 2 131 , Sebastopol, CA 95473. Ph : weekend a month intensive designed to teach the ington and Oregon on August 6-7. Registrat ion 707/579-6209. Emai l: autumnsu@aol. co m. therapeutic uses of over I 00 herbs. formula struc­ is $395. Co ntact Allured Publishing, 362 South ture, preparation, and diagnosis of co mm on dis­ Schmale Rd ., Carol Stream, IL 60 188-2787. Ph: September 5-8: Third Annual Jntemational harmonies. Tuition $875. Call CIHS at 860/666- 630/653-2 155. Fax: 630/653-2192. Congress on Alternative and Complementary 5064. Therapies, at the Crystal Gateway Marriott in August 6: Traditional Chinese Medicine Theory, Arlington, VA . Sponsored by the bimonthly pub­ September 27-28: Power of Herbs, 6th Annual Connecticut Institute of Herbal Studies. Learn li cati on, Alternative and Complementary Thera­ Weekend of Healing Plants Workshops, ew the terminology and principles of Chinese medi­ pies, th e meeting fo r alternati ve and mainstream York Botanical Garden, Bronx, NY. Learn abo ut ci ne. A six week, one ni ght a week class, and practiti oners focu ses on proven strateg ies for trad itional herbal therapi es an d healing arts in prerequi site fo r the Chinese Herbology class in "Delivering Pat ient-Centered Complementary these workshops on the power of plants to pro­ Sept. Tuition $259. CIHS , Newington, CT. Ph: Healthcare." Designed to meet th e growing in­ mote health and we ll-being. Call Continuing 860/666-5064. formation and educational needs of the full spec­ Education at 718/8 17-8747. trum of today's healthcare providers. Contact August 15-17: HerbFest '97, Preserving the Susan Vega at BioConferences International, 800/ September 29-30: Dietary Supplements: Inno­ Balance-Body, Spirit, Earth. Hosted by Fron­ 5-B IOCON, 914/834-3100. Fax: 9 14/834-3689. vative Marketing and Promotion Strategies, tier Herbs, thi s sixt h annual weekend conference Watergate Hotel, Washington. D.C. Learn to meet will explore how herbs can bring balance to our September 6-7: First Annual Congress on Natu­ regulatory and legal challenges head on. Speak­ li ves. Semin ars, workshops, herb walks, herbal ral Pharmacy, Arlington , VA. Contact atural ers include Loren lsraelsen and Mark Blumen­ bazaa r. Camping ava il able and special program s Pharmacy at 914/834-31 00. thal. Contact: IBC Conferences, 508/481-6400. for kids. Contact Frontier Herb Fest '97, 302 1 78th Fax: 508/481-7911 . St. , P.O. Box 299, Norway, lA 523 18. September 12-14: Applied Ayurvedic Medicine, a practical course for li censed health profession­ October 5-15: Herbal Seminar in Greece. Join August 20-24: American Association of Naturo­ als, Calistoga, CA. First of three sessions for a Cascade Anderson Geller on this unique Med i­ pathic Physicians' Annual Convention, total of 54 hours. Dr. Vivek Shanbhag, N.D., M.D. terranean adventure. Seminar highlights incl ude Scottsdale, AZ. Contact AANP, 206/298-0 126. (Ay urved), in structor. In stitute of Medical herb identification, Hippocratic and Greek medi­ Fax : 206/298-0129. Emai I: Herbalism . Ph : 707/942- 1250. cine. local cu linary and medicinal herbs. and [email protected]. herbal healthcare for trave lers. Meet local people. September 20-21: Clinical Applications ofNa tu­ exchange ideas. and experience village life on the August 22-24: lOth Annual Women's Herbal ral Medicine, a Co nference for Healthcare Pro­ Aegean islands Ikaria, Samos, and Patmos. Con­ Conference: A Celebration of Women 's Health, fessionals, Chicago. Presented by The American tact Traditional Tours at 800/639-2693. Herbs, and Healing, in the Monadnock region Journal ofNat ural Medicine, the co nference goal of southern New Hampshire. Leading women is to educate healthcare professionals about the October 6-7: Hemp industries Assoc. Conven­ herbalists and healers share their wisdom of plants practical applications of natural medicine, includ­ tion, Sonoma Count y, CA. Contact HIA at 500/ and natural healing methods. Teachers include ing the latest, most inn ovative advancements in 442-4367. Dr. Ros ita Arvi go, Amanda McQuade Crawford, th e field. Speakers incl ud e Mark Blumenthal ,

HERBALGRAM No. 40 • 67 CALENDAR

October 14-15: Cardiovascular Nutraceuticals: November 10-15: Second World Congress on 1998 Their Proper Role in Health and Medicine, Medicinal and Aromatic Plants for Human Wel­ January 8-10: Antitumor Products from Higher Eighth Annual Nutraceutical Conference, Wash­ fare (WOCMAP II), Mendoza, Argentina. This Plants, Paris, France. Biosynthesis and activity ington, D.C. Sponsored by The Foundation for symposium will focus on medicinal and aromati c of anticancer compounds extracted from hi gher Innovati on in Medicine, 411 North Avenue East, plants as biological resources, developments in plants. Phytochemical Society of Europe. Con­ Cranford, NJ 07016. Ph: 908/272-2967. Fax: 908/ agri cultural methods, searches for novel com­ tact: Professor F. Tillequin, CNRS URA 1310, 272-4583. pounds, pharmacology and toxicology, industrial Faculte de Pharmacie, Universite Rene Descartes processing, quali ty control, marketing, and con­ - Paris V, 4, rue de l'Observatoire, 75270 Paris October 14-I8: The Power of Healing: Science, servation. Contact WOCMAP II , Jose Hernandez cedex 06, France. Ph: 33 I 43 29 12 08. Fax: 33 Nature & Spirit, Boston. Four-day intensive 162 1, 6th fl oor A, 1426 Buenos Aires, Argentina. I 40 46 96 58. seminar with Dr. Christiane Northrup and Dr. Ph: 54 I 786-6528. Fax: 54 I 78 1-6907. Email: Andrew Wei!. Learn costs and benefits of tradi­ time@ starnet. net.ar. February 16-20: International Conference on tional and natural medicine, how to prevent dis­ Medicinal Plants Conservation, Utilisation, ease and promote health, nature's healing wisdom November 10-20: Medicinal Plants of the Holy Trade & Biocultures, Bangalore, South India. and power, herbs everyone should know, and Land, Biblical Botany Tour. Join renowned eth­ Hosted by the Foundation for Revitali sation of more. Contact Feathered Pipe Foundation, PO. nobotanist Dr. James Duke and hi s artist wife Local Health Traditions, bringing diverse bio-cul­ Box 1682, Helena, MT 59624. Ph: 406/442-8 196. Peggy as they update their Medicinal Plants of tural concern s related to medicinal plants together Fax: 406/442-8110. Email: [email protected]. the Bible book. A ten-day eco-tour of Israel vis­ under the 1998 theme "Medicin al Plants for Sur­ iting the most important sceni c and scientific vival. " Contact FRLHT, No. 50, 2nd Stage, 3rd October 17-19: Applied Ayurvedic Medicine, a sights. Daily lectures in a biblical setting on bib­ Main, MSH Layout, Anandnagar, Bangalore - practical course for li censed health professionals, li cal botany (with checklist of 175 plants of the 560024, India. Email: [email protected] Calistoga, CA. Second of three sessions for a to­ Holy Land), medi cin al herbs, and nutritional ap­ tal of 54 hours. Instructor, Dr. Vivek Shanbhag, proaches to better health. Call Evelina at Valley March 13-15: 1998 international Conference .D., M.D. (Ayurved). Insti tute of Medical Travel Group for information and brochure. Ph: on Phtyotherapeutics, sponsored by the National Herbalism. Ph: 707/942-1250. 800/348-7865. Herbali sts Association of Australia, Sydney, Aus­ tralia. Herbal medicines and their appli cati ons. October 17-20: EighthAnnualAmerican Herb­ November 14-16: Synergia '97, an International Contact Conference Coordinator, 1998 Interna­ alists Guild Symposium, cosponsored by the John Conference and Trade Show on Education and tional Conference, P.O. Box 403, Morisset, Aus­ Uri Lloyd Library and Museum and the Ameri­ Research in Aromatherapy. Sponsored by the tralia 2264. Ph: 61 49 734107. Fax: 61 49 can Botanical Council. Over 25 teachers, 40 semi­ American Alliance of Aromatherapy, the Aromatic 734857. Email : [email protected]. nars, 4 panel discussions. Academic poster ses­ Thymes, and the Natural Oils Research Associa­ sion, bookstore and herbal exhibits, plus seven tion. Contact Jade Shutes, 604/267-7433 or August 2-7: XXV International Horticultural scheduled one-hour tours of the John Uri Ll oyd Charl a Devereoux, 9 14/838-4340. Congress, Brussels, Belgium. Scientists will ad­ Library and Museum. Contact Rebecca Briggs/ dress state of the art horticultural research. Con­ AHG Symposium Coordinator, 328 1/2 Liberty November 14-December 29: Travels to China, tact H. Wilcox, Secretary 25th !HC, c/o Ministry St., Ashland, OR 97520. Ph: 54 1/488-6260. Fax: Chengdu University ofTraditi onal Chinese Medi­ of SME and Agriculture, Bolwerklaan 2 1, 15th 54 1/488-6459. E-mail: A HG97@aol. com. cine, the most traditi onal Oriental Medical school Floor, B-1 2 10 Brussels, Belgium. Fax: 32 2 206 Website: http://www .healthy. net/herbalis t/ in China. Training for the practitioner or advanced 7209. Email : 25 [email protected]. Website: http/ ahg97.ht. student in Oriental Medi cine, with courses ori ­ /:www.agr.kuleuven. ac.be/ishs/ishshome.htm. ented in clinical practice and herbal training. October I8-25: 4th Annual Peruvian Amazon Contact Academy of Oriental Medicine, P.O. Box Rainforest Ethnobotanical Expedition. Explore 9446, Austin, TX 78766. Ph: 512/454- 11 88. CLASSIFIED the 1/4-mil e Canopy Walkway over 115 feet above the rainforest floor. Workshop leaders include Dr. November 21 -23: AppliedAyurvedic Medicine, CORRESPONDENCE COURSES Jim Duke, Dr. Varro Tyler, Christopher Hobbs, a practical course for li censed professionals, AND SEMINARS Dr. Larry Wilson, and Mark Blumenthal. Con­ Cali stoga, CA. Final session for a total of 54 Aromatherapy Studies Course/Jeanne Rose. tact the American Botanical Council, P.O. Box hours. In structor, Dr. Vivek Shanbhag, N. D. , Corresponde nce, certificati on, in-person 20 I 660, Austin, TX 78720. Ph: 512/331-8868. M.D. (Ayurved). In stitute of Medical Herbal ism. intensives. 160 CEU provided, California Board Fax: 5 12/331- 1924. Ph : 707/942- 1250. of RN Provider #CEP11659. In fo: 2 19 Carl St., San Francisco, CA 94117 or FAX 4 15/564-6799. November4-6: International Workshop on Pros­ December 11-12: 4th Annual Symposium on pects of Medicinal Plants in Providing Health Complementary Health Care, University of Green Terrestrial offers herbal and earth aware­ Care by 2000A.D. and Beyond, Solan, Himachal Exeter. A forum for researchers in all areas of ness workshops, quality herbal products, and ap­ Pradesh, India. Sponsored by the International Complementary Medicine to present new data. prenticeships in an atmosphere of co-creative Union of Forestry Research Organizations Contact Mrs. E. Stewart, Symposium Secretary, partnering with the Earth. Pam Montgomery, P.O. (IUFRO). Contact Dr. P. L. Gautam, Organisin g Dept. of Complementary Medici ne, Postgraduate Box 266, Milton, NY 12547. 914/795-5238. Secretariat, DRYS Parmar Un iversity of Horti ­ Medical School, University of Exeter, 25 Victoria culture & Forestry, Nauni 173230 Solan (HP), Park Road, Exeter, Devon EX2 4NT, UK. Email : Grow Gourmet & Medicinal Mushrooms. India. Fax: 91 1792 6 2242. [email protected] Shiitake, Reishi , Morels, Oysters .... Seminars on culti vation. Free brochure. Commercial catalog $4.50. Fungi Perfecti , P.O. Box 7634HG, Olym-

68 • HERBALGRAM No. 40 CLASSIFIED

A listing in th is classified section does not constitute any endorsement or approval by Herbo/Grom, the American Botanical Council, the Herb Research Foundation, or the HRF Professional Advisory Board. Herbo/Grom Classified ad rates: $1.25 per word; $35 minimum . Contact Margaret W right, P.O. Box 201660, Austin, TX 78720. 512/331-8868. Fax 512/331-1924.

pia, WA 98S07. Call 8001780-9126. Fax 360/ The Business of Herbs - Comprehensive report­ inspire, and advance the field of aromatherapy. 426-9377. ing, business news, marketing hints, sources, and Offering the following publications to keep you resources. Subscription $24/yr. Brochure/SASE updated with aromatherapy developments world­ Institute of Chinese Herbology has been teach­ from Northwind Publications, 439 Ponderosa wide: The Alliance News Quarterly, Th e Aromatic ing courses in Chinese Herbal Medicine since Way, Jemez Springs, NM 87025. Thymes, Th e International Journal of 1986. Our 130-hour audiotaped program (includ­ Aronwtherapy, The Aromatherapy Guide - 2nd ing extensive notes and herb samples) is excel­ Foster's Botanical and Herb Reviews- Infor­ Edition, and The Aromatherapy Records. For in­ lent for anyone who wants to gain a working mation resources, book reviews, new periodicals, formation, including a complimentary issue: 800/ knowledge of Chinese herbs. Free brochure: etc. Quarterly, $1 0/yr from Steven Foster, P.O. 809-98SO, Fax 800/809-9808. Admissions 2HG, 3871 Piedmont Ave., #363, Box 1343, Fayetteville, AR 72702. SO IIS21- Oakland, CA 94611. Ph./Fax 510/428-2061 . 5887. Fax 5011521-6369. Journal of Herbs, Spices & Medicinal Plants­ A comprehensive quarterly forum filled with re­ The School of Natural Healing was founded in HerbalGram - Quarterly journal published by cent research and valuable information about 1953 by Dr. John R. Christopher, M.H., N.D., and the American Botanical Council and the Herb herbs, spices, and medicinal plants. Special rates: continues in his time-tested modalities. The SNH Research Foundation. $25/yr., $4S/2 yrs, $60/3 $3611 volume (save $4); $64/2 volumes (save offers Master Herbalist (M .H.) training in 18 yrs. P.O. Box 201660, Austin, TX 78720. 800/ $ 16); $84/3 volumes (save $36) (4 issues per vol­ course levels at $100 each. This full spectrum of 373-7105 or fax Sl2/331-1924. Includes center­ ume; U.S. individual subs only). Pharmaceutical courses is taught by expert instructors, in the con­ fold pull-out Herbal Education Catalog with or­ Products Press, IOAiice Street, Binghamton, NY venience of your own home, on professionally dering information. 13904- 1580, Tel: 800/HAWORTH , Fax: 800/895- produced video and audio tapes. Books, work­ 0582. Free sample issue also available. books, and home assignments are also provided. HerbalVoices: The Journal of Self-Reliant Upon completion of the 18 courses, students are Herbalism. Sample Issue $3. Yearly subscrip­ Medical Herbalism - Subtitled "A Clinical eligible to attend the intensive certification semi­ tion $ 12. Published Quarterly. 3936 Mt. Bliss Newsletter for the Herbal Practitioner." Edited nar held at our own beautiful retreat in the majes­ Rd., East Jordan, MI 49727. by Paul Bergner. $24/yr, $42/2 yrs. Canada $29/ tic Wasatch Mountains. For free information, call yr. Overseas $39/yr. Sample/$4. Medical 11800/372-8255 or write to the School of Natural Herban Lifestyles - Bimonthly newsletter with Herbal ism, P. 0. Box 33080, Portland, OR 97233. Healing, P.O. Box 412, Springville, UT 84663. entertaining, eclectic, and sometimes esoteric re­ ports on how we li ve, work, and play with herbs. Robyn's Recommended Reading- A quarterly Money-back guarantee. Sample $3. $ 18/yr. Free review of literature relating to herbali sm and PUBLICATIONS brochure. Stone Acre Press, 84 Carpenter Rd., phytotherapy. Keep up to date with books, jour­ American Herb Association Quarterly Newslet­ Apt. 78711-1, New Hartford, CT 06057. nal s, newsletters, magazines, web pages, and other ter-$20/yr. AHA, P.O. Box 1673, Nevada City, sources of information. $ 15/yr for 4 issues, $20/ CA 95959. The Herb Growing and Marketing Network­ yr International. U.S . funds only. RRR, 1627 W. An information service for herb businesses and Main, Ste. 116, Bozeman, MT 59715. Aromatherapy Quarterly Magazine - Presti­ serious hobbyists. Includes The Herbal Connec­ g ious English journal, the longest-running tion, a 36-page bimonthly trade journal, Th e Washington Insight - A qu arterly newsletter aromatherapy magazine in the world; read in over Herbal Green Pages, annual resource guide with designed to keep natural products scientists SO countries by aromatherapists, herbalists, mas­ over 5,000 li stings, free classified advertising for abreast of important happenings in Washington, seurs, and medical practitioners. A world-class subscribers, and more. Entire package $60/yr. D.C., that may affect them and their institutions. resource for the latest developments in (Higher outside North America) Sample news­ Read interviews with Congressmen, Senators and aromatherapy; beautifully crafted, filled with prac­ letter, $4. The Herbal Connection, P. 0. Box 245, government officials; reports on key Congres­ tical information. Subscriptions $30. 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Regular Sample issue $5; introductory subscription (5 is­ eign: personal/$52; institutional/$95. Contact: features include Australian medicinal plants, con­ sues) $ 19.95. P. 0. Box 689, San Anselmo, CA Washington In sight, II 000 Waycroft Way, North ferences, conference reports, book reviews, rare 94979. 11800/371-HERB. Bethesda, MD 20852. 3011881-6720, Fax: 30 II books, case study and medicinal plant review. 984-7372. Aus/$40 plus Aus/$15 if required by airmail. Join the Aromatherapy Revolution! - The National Herbalists Association of Australia, American Alliance of Aromatherapy, a non-profit Wildflower - North America's only popular Suite 305, 3 Smail St., Broadway, NSW 2007, organization, has been established to strengthen, magazine devoted solely to the study, conserva- Australia.

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70 • HERBALGRAM No. 40 EDIBLE WEED

~ 0i111g111g Xeiile ~ Urtica dioica L. (Urticaceae}

· UTILITY: I am probably the only forager you'll read about in Urtica, U. charrwedryoides Pursh., the Southern Nettles; U.lyallii who has eaten the stinging nettles raw, although most foragers have Wats., the Lyall Nettle; and U. urens L., the Burning Nettle. enjoyed them cooked. (Julie Summers may have reported a raw nettle repast somewhere in the pages of Coltsfoot.) The raw nettles DISTRIBUTION: Rich, alluvial meadows and forests, espe­ quit stinging by the time they get to the throat, at least in my trials. cially common in disturbed areas, often forming dense stands, spread­ The nettles are easy enough to secure in summer as ing by underground rootstocks, flowering from May to July in North vitamin-rich potherbs. Once you know where the solid stands are, Carolina, from June to July in Maryland, the fruits ripening from you can try an old Scots trick. Go dig up the roots when the ground July to September. Range: Washington east to Maine; south to New is thawed in winter, taking them to a dark cellar. It won't be long Mexico, east to Florida. From central Alaska south and east; Hardy before you have blanched nettle to mix with your blanched pokeweed. in zones 1-8, temperatures from -40° to 20°. I hardly need to do that in Maryland, at least under global warming. MynettlespersistedintoJanuaryl99l,onthesouthsideofthebarn DESCRIPTION: Perennial herb to nearly 6 feet tall. at Herbal Vineyard, and new shoots were up the following months, LEAVES: 2 at the node, opposite each other on the stem, the lower in a warm winter of the warmest year on record. Nettle juice can be leaves 2-5 inches long, 13 inches wide, broadly egg-shaped, broad­ used to coagulate milk. est below the middle, with a point drawn out at the tip, coarsely I have read that different ethnic groups, scattered all over the . toothed along the margin, with a heartlike notch where the leafstalk world, use the stinging hairs as a counterirritant in arthritis. Several attaches to the blade, with 3-5 nerves arising where the leafstalk people I know who tried this now keep nettles in their kitchen win- joins the blade, the upper leaves smaller and proportionately oar­ dow beside the aloe. The mother v•-·1UJ¥.lLIUUl "--l-".. -J.:,L..uJ. •..J.j .~"' -~·««1ll<>1l,...1Ju...... ,,.f'" '· "'' in the angle formed by the needs the nettle, though it is now a the leafstalks, the male and arthritis went away. My flowers with 4 sepals and 4 not seem to respond. 4 sepals and a !-celled ovary Heinerman (1988) suggests . FRUIT: a small, !-seeded Nettle Ale, boiling down 2 gallons by 2 expanded sepals. fresh nettle greens, 2 lemons, 3 A. Duke. ounces ginger root, 2 cups brown by Peggy Duke from a little nutmeg and mace, primed Peggy Duke's Green Pharrrwcy, a cake of active yeast. Euell Press, Emaus Pa. 1997 (Aug.) recommended nettle for ob (Heinerman, 1988). Elias, T and P. Dykeman. Most medical doctors would Edible Wild Plants. A North vise against self-diagnosis and"'"'"""'~ Field Guide. Sterlip.g tion, let alone self urtication. But I ~ull<>l.ll.l•e,Co ., New York. 288 pp. centl y learned that the sting of the simulates the effect of acupun This article is part of a se­ electrostimulation, or ultrasound in of excerpts from The Hand­ leviating the cramps and pain of Edible Weeds, 1992, CRC ated with a herniated disk. Any of Inc., and is presented with three will cause twitching in modifications with perrnis­ cramped muscles and numb limbs of CRC Press and James and have accompanied my slipped­ Duke. The Handbook of problem. The Weed Science Society Weeds is available from the America (WSSA) lists 3 other Catalog, #B024.

HERBAtGRAM No. 40 • 71 7/ie

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