ETHNOPHARMACOLOGY OF MEXICAN ASTERACEAE (COMPOSITAE

P1: ARS/VKS P2: NBL/DAT QC: NBL/anil T1: NBL

February 17, 1998 16:48 Annual Reviews AR053-20

Annu. Rev. Pharmacol. Toxicol. 1998. 38:539–65Copyright c© 1998 by Annual Reviews. All rights reserved

ETHNOPHARMACOLOGYOF MEXICAN ASTERACEAE(COMPOSITAE)

Michael HeinrichInstitute of Pharmaceutical Biology, Albert-Ludwigs University, Schaenzlestrasse 1,79104 Freiburg, Germany

Mario RoblesDepartment of Pathology, Room D440, Medical Science I, College of Medicine,University of California, Irvine, California 92717-4800

Jan E. WestDevelopmental and Cell Biology, School of Biological Sciences, University ofCalifornia, Irvine, California 92717

Bernardo R. Ortiz de MontellanoDepartment of Anthropology and Center for Chicano-Boricua Studies, Wayne StateUniversity, Detroit, Michigan 48202

Eloy RodriguezL. H. Bailey Hortorium, Division of Biological Sciences, Cornell University, Ithaca,New York 14853-2703

KEY WORDS: Mexico, sesquiterpene lactones, natural products toxicity, natural productpharmacology, ethnobotany

ABSTRACT

Traditional herbal remedies have increased in popularity in Europe and the UnitedStates in recent years but have always been important to people living in ruralMexico and to their Mexican American/Chicano descendants in the United States.Mexican American patients will often be ingesting herbal teas at the same timethat they are being treated for their ailments with antibiotics or antiinflammatoryagents. The plant family Asteraceae (Compositae) has contributed the largestnumber of plants to this pharmacopoeia; the reasons for the importance of thisfamily include its large number of species in Mexico and its wide array of natural

5390362-1642/98/0415-0539$08.00

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540 HEINRICH ET AL

products that are useful in the treatment of the maladies that have afflicted theinhabitants of rural Mexico. These natural products include sesquiterpene lac-tones, polyacetylenes, alkaloids, monoterpenes, and various phenolics such asflavonoids. In this review, we emphasize the sesquiterpene lactones, a largegroup of compounds with antiinflammatory properties and the ability to relaxsmooth muscles and thereby relieve gastrointestinal distress. These compoundsalso readily form adducts with glutathione or free thiols and can thereby af-fect the metabolism, activity, and toxicology of a wide array of pharmacologicalagents.

INTRODUCTION

The principal reason for focusing a major review on Mexican Asteraceae (Com-positae) is the enormous importance of these plants in the popular medicineof Mexicans and Mexican Americans/Chicanos in the United States. Mem-bers of this botanical family, such as wormwood (Estafiate,Artemisia ludovi-cianassp.mexicana), zoapatle (Montanoa tomentosa) and Mexican arnica (Het-erotheca inuloides), are frequently sought by people who have health problemsfor which they do not want to consult a doctor or a health center. Therefore, itis important to the health of these peoples that the medical community have asummary of the pharmacological effects and potential side effects of theseplants. This review is necessarily limited by the relative paucity of knowledgeof the total chemical constituents of these plants and the diverse effects of thesenatural products. Although thousands of scientific articles have been publishedon natural products, each plant has several hundred different natural products,the great majority of which have not been studied. Many of the plants usedin folk remedies are potentially hazardous and have chemical constituents thatcan elicit allergic contact dermatitis (e.g.Parthenium hysterophorus) or liverdamage (from pyrrolizidine alkaloids) (1). The review is limited to speciesnative to Mexico and is divided into two major parts: (a) an initial descriptionof the major types of chemical compounds and their major pharmacologicaleffects; (b) nine summaries of existing information about plant genera usedmost widely in popular medicine of modern and historic Mexico.

Many of these plants have no popular name that is consistently used inEnglish; in other cases the English name may refer to two or more botanicallydistinct species (e.g. arnica). Therefore, the species are grouped alphabeticallyaccording to their botanical name. We use the current taxonomic names wher-ever possible. If other names were used by the authors of previous papers, theyare given as synonyms. English, Spanish, and Native names are given in thetitle of each summary whenever possible.

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MEXICAN ASTERACEAE 541

Ethnobotany of the AsteraceaeThere are about 380 genera with 3000 species currently (1994) recognized inthe Asteraceae in Mexico (J Villase˜nor, unpublished data). The Asteraceaehave yielded an astounding number of medicines for the native and mestizopopulations of Mexico, and numerous studies have been conducted on the usesof these plants in the various regions of Mexico. An important prerequisite forthese studies is a detailed knowledge of which plants are of major ethnobotanicalimportance and which are used only by a few people of a community and/orby only a few indigenous or mestizo populations. While there are numerousreviews of plants traditionally used in North America and Europe (2, 3), nomodern comprehensive treatment is available for Mexico. This review is partlybased on a review on the ethnobotany of Mexican Asteraceae prepared byHeinrich (4). He used data from both historic and modern sources to selectthe most widely used plants for this review. The Asteraceae is subdivided intoseveral “tribes,” or subgroups, which have characteristic differences in theirphytochemistry (e.g. Senecioneae-pyrrolizidine alkaloids).

Asteraceae in Mexico, Historical and Modern UsesThe most important source of our knowledge about indigenous plant use inhistorical Mexico is the Florentine Codex compiled by the Franciscan monkFray Bernardino de Sahagun. Also important are the work of the Spanishphysician Francisco Hernandez and a herbal guide written in Nahuatl by theAztec healer Martin de la Cruz from Tezcoco that was translated into Latin byJuan Badiano and sent to the King of Spain, Philip II, in 1552.

In the past 20 years, numerous studies have examined the traditional uses ofplants in many parts of the highlands of Mexico and also, though less frequently,in the deserts and the tropical parts. Such studies were conducted not only inareas with large indigenous populations but also in the markets where medicinalplants are sold. These studies are rather diverse in methodology (5, 6); some arebotanically oriented with little ethnographic information (7), while other havea strong ethnographic background (8). Other studies do not focus specificallyon medicine and plants, but yield relevant information (9).

MAJOR CLASSES OF CHEMICAL COMPOUNDSREPORTED FROM THE ASTERACEAE

Sesquiterpene LactonesSesquiterpene lactones (SQLs) are a large and diverse group of biologicallyactive plant constituents that have been reported from 10 families of floweringplants; however, the greatest number are derived from the Asteraceae, with

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542 HEINRICH ET AL

over 3000 reported structures. Some of the important medicinal plants fromthis family, such asArnica montana, Artemisia annua, andTanacetum parthe-nium, contain SQLs as the active constituents. SQLs are commonly present inlarge quantities (>2% dry wt of leaves); these SQLs are usually comparativelynontoxic but have an intensely bitter taste that presumably deters herbivores.A few SQLs are highly toxic (e.g. repin, helenalin), but many have antiinflam-matory activity and relax smooth muscle in vitro. Previous major reviews byRodriguez et al (10), Fischer et al (11), Seaman (12), and Picman (13) discussedthe chemistry and taxonomic significance of SQLs; Stuppner & Rodriguez (14)and Picman (13) reviewed recent aspects of the biological activity. An im-portant research objective of the laboratory at Cornell has been the study ofthe biochemical mechanism of action of SQLs. These studies have suggestedthat cytotoxicity is mediated by the interaction of the active moiety (exocyclicdouble bond conjugated with carbonyl carbon of lactone ring) with enzymesbearing a sulfhydryl group (10). This interaction inhibits enzyme activities andmetabolism, and interactions with glutathione (GSH) (15). Common proper-ties of many of the pharmacologically active SQLs are antiinflammatory effectsmediated by inhibition of prostaglandin synthesis and a stimulation of smoothmuscle contractions. Recently, it was also shown that SQLs are potent andspecific inhibitors of the antiinflammatory transcription factor NF-κB (15a–c).One of the potential sites of action of antiinflammatory drugs is this transcriptionfactor. It is essential in immune-, inflammatory-, and acute-phase responses,where rapid activation of defense genes following exposure to pathogenes suchas bacteria and viruses is necessary for the survival of the whole organism(15b). Activation of the factor leads to gene expression of several interleukingenes, which then produce the inflammatory response. Both of these proper-ties could explain the popularity of SQL-containing herbal remedies to treatgastrointestinal distress.

ANTITUMOR ACTIVITY Kupchan et al (16) demonstrated that SQLs have bothcytotoxic and antitumor activity. To date, few data have been published on thein vivo antitumor properties of SQLs. In 1982, Towers et al (17) reported thatnonlethal doses of parthenin have a significant effect on the survival of micewith tumors derived from either L1210 or P815 tumor cells. Hladon & Chodera(18) revealed that eupatoriopicrin can prolong the life expectancy of mice aftertransplantation of the tumors Sa180, EAT, and L1210. In 1987, Woerdenbaget al (19) reported that eupatoriopicrin possesses potent antitumor activity inthe Lewis Lung tumor system in mice, an experimental solid tumor systemderived from a malignant and poorly differentiated epidermoid human carci-noma. They concluded that eupatoriopicrin had a cytostatic effect against thesolid tumor growth when injected intraperitoneally (i.p.) to C57Bl/6j mice (19).

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The methanolic flower extract ofParthenium hysterophorushas been foundto have in vivo antitumor effects against P388 lymphocytic leukemic cells inmice. Biochemical markers such as reduced GSH, cytochrome P450, GSHtransferase, and UDP-glucoronyl transferase in the liver of host cells showedsubstantial alterations leading to slow development of tumors and an increase inthe survivability of the mice bearing the lymphocytic leukemia. More researchon the in vivo antitumor properties of SQLs is needed.

ANTIULCER ACTIVITY Plants containing SQLs have been used as herbal reme-dies in different cultures. In Argentina, leaves ofArtemisia douglasianahavebeen used to prepare an infusion called “matico” that is used to treat peptic ul-cers and external sores and ulcers. The in vivo gastric cytoprotective propertiesof matico were investigated by Giordano et al in 1990 (20), who demonstratedconsiderable protective effects in rats against ulcerogenic agents such as ab-solute alcohol. The crude chloroformic extract (containing SQLs) ofA. dou-glasianaexhibited significant protective activity, and upon chromatographicpurification, a sesquiterpene lactone, dehydroleucodin, was isolated. Furtheroral testing demonstrated that this lactone was the antiulcer agent inA. dou-glasiana, and the protective effect was shown to be dose dependent. Giordanoet al (20) speculated that the antiulcerogenic activity is related to the induc-tion of endogenous prostaglandin release. They observed a reduction in theprotective effect when rats were pretreated with indomethacin, a prostaglandininhibitor.

Giordano et al (20) investigated the activity of other SQLs with ludartin, aguaianolide, hymenin, mexicanin I, helenalin, and 9-O-desacetylspathulin-2-O-angelate and showed protective activity similar to that of dehydroleucodin,while the lactone desacetoxymatricarin lacked protective effects. Giordano et alconcluded that theα-methylene-γ -lactone moiety is required for the protectiveeffect. In 1992, Giordano et al (21) revised the proposed mode of action andspeculated that the protective effect was mediated by more than one mechanism.Aluminum hydroxyl, a commonly used ulcer medication, exerts its protec-tive effect in a similar fashion by both stimulating prostaglandin release andforming adducts with the thiol constituents in the gastric mucosa. These thiolconstituents are also capable of reacting with the lactones. Structure-activitystudies with 18 SQLs led Giordano et al to conclude that the presence of a non-sterically hindered Michael addition acceptor,α-methylene-γ -lactone moiety,is a requirement for the cytoprotective activity (21).

CARDIOTONIC ACTIVITY The presence of the azulene skeleton in many SQLsstimulated researchers to investigate the effects of azulene-containing SQLs onisolated heart muscle. Strips from the left atrium and papillary muscles from

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the left ventricle of the guinea-pig heart were used to examine the effect ofhelenalin, a sesquiterpene lactone isolated fromHelenium autumnale, on theircontractility. Helenalin was shown to produce a positive ionotropic effect (PIE)on both. This PIE is dose dependent, with concentrations effective on the atrialstrips in the range between 10−5 and 3× 10−4 M, and on the papillary musclein the range between 3× 10−4 and 10−3 M. Furthermore, in this system thePIE is persistent and does not return to control after washing the preparations.The dependency of PIE on catecholamines in atrial but not in ventricular mus-cles was shown in reserpinized guinea-pigs. Studies to investigate the modeof action of helenalin concluded that helenalin increases cAMP by inhibitingphosphodiesterase (22). This increase of cAMP causes Ca2+ influx and therebyenhances the contractility of the myocardium.

NEUROTOXICITY Several plant toxins have been associated with neurodegen-erative changes in both brain and spinal cord. Until recently, no SQLs have beendirectly associated with neurological disorders. However, in 1954, a specificneurological disease of horses commonly known as “chewing disease” was ex-perimentally linked to the ingestion of large amounts ofCentaurea repens(23),a member of the Asteraceae with large quantities of SQLs. Neuropathologicalexamination of the brain from an intoxicated horse revealed bilateral necrosisof the anterior globus pallidus and zona reticulata of the substantia nigra. Topursue the hypothesis that SQLs might produce neurotoxic effects, Stevens &Riopelle (24) conducted an in vitro neurotoxicity study. They observed thegrowth of the neurites in the presence of the different SQLs fromC. repensandestimated the 50% toxic dose (TD50). On a molar basis, repin was 3–4 timesmore toxic than its C-17 isomer subluteolide and 4–10 times more toxic thanacroptilin and the other SQLs tested. In 1991, Wang et al (25) studied the neu-rotoxic effects of SQLs from yellow star thistle (Centaurea solstitialis). Theyreported that solstitialin cynaropicrin exhibited toxicity to cultured rat fetal braincells in a concentration-dependent manner and suggested that these compoundscould cause neurodegenerative disorders. In the laboratory, Robles, Choi, andcolleagues have demonstrated cytotoxicity to different cell lines, specificallyto brain cells (26, 27). They also demonstrated that repin can deplete levels ofintracellular GSH in mice both in vitro and in vivo. Depletion of GSH reducesthe protection from oxidative stress; therefore, repin neurotoxicity could bemediated by the depletion of intracellular GSH.

ANTIMIGRAINE ACTIVITY Tanacetum parthenium, commonly known as “fev-erfew,” is widely consumed in England and other regions of northern Europeas a remedy for arthritis and migraine headaches. Several reviews ofT. parthe-nium have been published recently in which the botany, phytochemistry, and

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pharmacology are highlighted (28–31). Heptinstall et al (32) reported thatparthenolide (a SQL) was the active constituent in feverfew. Parthenolide hasbeen shown in vitro to inhibit prostaglandin synthetase, thereby relieving in-flammatory conditions such as arthritis (33). Clinical evidence has demonstratedthe efficacy of feverfew in 17 migraine patients (34). Other clinical studies havedemonstrated that parthenolide reduces the incidence and severity of migraines(34, 35). Because of the beneficial effects of feverfew in clinical settings,parthenolide’s biological properties have been extensively investigated in thepast 10 years in an attempt to understand its prophylactic activity. Parthenolidecan inhibit platelet aggregation and serotonin secretion in vitro when presentat micromolar concentrations (34). A decrease in serotonin levels in plateletsis the most consistent of the biological alterations observed in migraines (34)and is common to other drugs effective against migraines. Commercial prepa-rations of feverfew are available through pharmacies and health food stores inEngland. No serious side effects were reported in the clinical studies.

ALLERGIC CONTACT DERMATITIS SQLs have frequently been shown to causecontact dermatitis. This is presumably due to Michael addition reactions be-tween skin proteins and exocyclic double–bond present in SQLs. Several in-vestigators (36–39) have reported that the genusPartheniumcauses dermatitis,rhinitis, and hypotension. The contact allergen identified fromPartheniumisparthenin.

Pyrrolizidine AlkaloidsExtreme caution should be used if pyrrolizidine alkaloid–containing plantsof the Asteraceae are taken; species of the generaSenecio, Packera, andPsavaliumare used by Mexicans and Chicanos, and the pyrrolizidine alka-loids make these plants extremely toxic, producing liver necrosis and cirrhosis(40). The pyrrole metabolites, produced in the liver, are alkylating agentsthat can cross-link macromolecules and produce carcinogenic and mutageniceffects. Pyrrolizidine alkaloids have been reported from three unrelated flow-ering plant families: Boraginaceae, Fabaceae, and Asteraceae. In the case ofAsteraceae family, only theEupatoriaeaeandSenecioneaetribes have been re-ported to contain pyrrolizidine alkaloids. Representative pyrrolizidine alkaloidsreported fromSenecioandPackerainclude: senecionine (1), integerrimine (2),retrorsine (3), usaramine (4), and senkirkine (5) (Figure 1).

PolyacetylenesThe polyacetylenes are a large group of compounds that have been reportedin numerous species of the Asteraceae, Apiaceae, Campanulaceae and spo-radically in other plant families. The polyacetylenes are most often found inthe root tissue but are also reported at lower concentrations in the leaf tissue.

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546 HEINRICH ET AL

Figure 1 Representative pyrrolizidine alkaloids.

The polyacetylene compounds most frequently reported from the Asteraceaeof Mexico include trideca-ene-pentayne and the epoxides, epoxisulfones, dithi-ins, and polythiophenes derived from this compound. Rodriguez et al (41)investigated many of the properties of the dithiin-type compounds; the dithiincompounds are also called thiarubrine compounds because of the intense redcolor of these compounds. Their laboratory studies have demonstrated thatthe thiarubrine compounds have extremely potent cytotoxic, nematocidal, andfungicidal properties. Similar studies were conducted at the University ofBritish Columbia (41).

Falcarinol (Figure 2), a linear polyacetylenic compound found inPanax gin-seng, a plant used extensively in East Asia for medicinal purposes, has been

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Figure 2 Falcarinol.

investigated (42) and demonstrates antimicrobial, antifungal, and antibacterialactivities at 6–200 ppm. Hansen & Boll (43), Muir et al (44), and Kemp,Baba, and colleagues (45, 46) reported that falcarinol inhibits the formationof 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and thromboxane B2 inplatelet cells at concentrations of 2–200 mg/ml. This inhibition of arachido-nate metabolism and platelet aggregation was further confirmed by Teng et al(47). Lee & Huemer (48) studied falcarinol’s antineoplastic activity. The etherextracts ofP. ginsengwere injected i.p. (500 mg/kg per day) into mice inocu-lated with murine tumor sarcoma (S 180), adenocarcinoma 755 (CA755), orleukemia 1210 (L1210). The extracts were found to actively inhibit S180 andCA755 tumors, but they did not significantly prolong the mean survival timeof the mice inoculated with L1210 cells. A very similar compound, dehydro-falcarinone, occurs in many of the Asteraceae of Mexico.

GENERIC SUMMARIES

AchilleaTheAchilleagenus is distributed in temperate regions of the Northern Hemi-sphere, especially in Europe and Asia.Achillea millefoliumis a species fre-quently used in Europe and America alike. Many species of this genus are richin essential oil, SQLs, and flavonoids (48a).

ACHILLEA MILLEFOLIUM L. (ANTHEMIDAE)/YARROW (ENGL.)/ TLAQUEQUETZAL

In the Florentine Codex,A. millefolium L. (Anthemidae)/Yarrow (Engl.)/ Tla-quequetzal is listed as an internal remedy for cough and overeating (49, p. 193)and as an external remedy for aches all over the body, together with tonalxihuitla(Stevia aliciforlia), atzitzicaztli (Urera caracasana), atzomiatl (not identified),and lampblack axin (fat from the scale insectLlaveia axin) (49, pp. 152 and157). Hernandez (50, p. 172; 51, p. 212) describes the sap as diuretic andemetic. The plant was used to relieve the stomach and flatulence. It was to beapplied locally for scabies and itching of the face mixed with acuahuitl, eheca-patli (not identified) (52, p. 24r). During this century it has been used as bittertonic for nervous disorders (nerves), hemorrhage, colic of the stomach, and

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548 HEINRICH ET AL

Figure 3 Three new sesquiterpenoids.

hypochondria. Twenty grams of the leaves and flowers are used as an infusionagainst hemorrhage. A decoction of 10 g per liter of water serves to cleansewounds (53, p. 223; 54, pp. 900–1).

The methanolic extract was found to exhibit activity against mouse P388leukemia cells in vivo. Bioassay directed fractionation led to the isolationof three new sesquiterpenoids: achimilic acids A, B, and C (55) (Figure 3).BDF1 male mice, 6 weeks of age, were inoculated intraperitoneally with 106

P388 cells. Test compounds were also injected i.p. as a single injection onthe day following the tumor inoculation. Antitumor activity was evaluated bythe increase in life span (ILS) compared with that of the control animals. Theresults showed that at the 5 mg/kg dose, all three test compounds increased thelife span (ILS%) (test compound A: 34%, B: 39% and C: 35%). Doses of 20mg/kg lost their effectiveness and doses of 50 mg/kg proved toxic to the treatedmice.

ACHILLEA NANAL. (ACHILLEA AGERATIFOLIA) In vitro inhibition of cyclooxy-genase and 5-lipoxygenase by alkamides isolated fromAchillea nanaL. andAchillea ageratifoliahas been reported. These are the key enzymes of thetwo major pathways of arachidonic acid metabolism and are thus antiinflam-matory agents. The most potent inhibitor against cyclooxygenase enzyme wastetradeca-2E,4E-10Z-triene-8-ynoic acid pyrrolidide (Figure 4), which was iso-lated fromA. nana: 50 mg/ml showed a 60% inhibition. In addition, themost potent inhibitor of the 5-lipoxygenase enzyme was trideca-2E,4E-diene-8,10,12-triynoic acid piperride (Figure 5), which was isolated fromAchilleaspinulifoliaFenzl exBoiss. A concentration of 50 mg/ml caused a 64% inhibi-tion of arachidonic acid metabolism (56).

ACHILLEA FRAGANTISSIMA Cirsiliol, a flavone isolated fromAchillea fragantis-sima, caused a concentration-dependent relaxation of rat isolated ileum. Theeffective concentration (EC50) of cirsiliol for relaxation of ileal segments was

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Figure 4 Tetradeca-2E,4E-10Z-triene-8-ynoic acid pyrrolidide.

5.2± 0.9× 10−6 M (n = 6). It is thought that cirsiliol interferes with calciumchannels and thus inhibits Ca2+ influx from the extracellular compartment (57).

ArtemisiaThe genusArtemisiacontains more than 200 species that have been reportedfrom many parts of the world and has been selected for remedies by culturesthroughout the world for its medicinal properties. The reported active con-stituents of the genus include all the types of common natural products of theAsteraceae: SQLs, polyacetylenes, flavonoids, essential oils (monoterpenes),diterpenes, triterpenes, and coumarins. We have included aspects of recent stud-ies conducted with extracts of the genus to give an indication of the range ofbiologically active compounds that could be found in the Mexican species if anexhaustive study were to be conducted. (One particular compound fromA. an-nua, artemisinin, with antimalarial properties, is not discussed since it appearsto be restricted to Chinese species.)

ARTEMISIA LUDOVICIANANUTT. SPP.MEXICANANUTT (ANTHEMIDAE)/ WORMWEED

(ENGL.)/ESTAFIATE (SPAN.)/IZTAUYATL (NAHUATL) The Badianus Codex men-tionsArtemisia ludovicianaNutt. spp.mexicanaNutt (Anthemidae)/ Wormweed(Engl.)/Estafiate (Span.)/Iztauyatl (Nahuatl) as a part of a mixture with xox-ouhcapatli and quetzalxoxouhqui (not identified) for treatment of weaknessin the hands. The treatment also included putting one’s hands into an anthill(52, p. 50r). Hernandez (50; 51 p. 190) prescribes it to cure pain from cold,flatulence, colic, or intestinal pain. The Florentine Codex (49, pp. 165–66) pre-scribes it to clean urine, relieve fever, for coughs and for anguish in the heart.Iztauhyatll, together withTagetes lucida(yahuatli), was closely associated with

Figure 5 Trideca-2E,4E-diene-8,10,12-triynoic acid piperride.

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the Aztec rain god, Tlaloc, and had several functions in medicine and ritual be-cause of it.

Modern internal uses in MexicoMexicans generally use the infusion as a bitterstimulant and the powdered flowers as a vermifuge and stimulant. Because ofits spasmolytic properties, the aerial parts are popular for colic. Ruiz Salazar(58), for example, mentions the following ailments as treatable with this plant:lack of appetite, stomach ache and parasites, stomach and liver infections.On the market of Sonora (Mexico D.F.), the plant is sold for the treatmentof dysentery and vomiting. The flowers are used as tea for colic, dysentery,diarrhea, indigestion, pain, and stomach aches (59, p. 108; 60, pp. 43–44).Only a few scattered reports on other modern internal uses are in the literaturein Mexico: treatment of colds (59, 61), bronchitis (7), chest congestion (61),heart illnesses (54), and menstrual complaints (58).

Modern external uses in MexicoThe leaves are used as a decoction for wash-ing the ear and as an analgesic by the Zoque (Chiapas). Kept in alcohol, theleaves are used for external cleansing (62). The Huastec use the leaves to treatearache, swellings, infections, and inflammations (9). In Veracruz the plant isused to treat headaches, sudden fright, and earaches (7).

The species has been studied in great detail, and the samples seem to differconsiderably in chemical composition. Jakupovic et al (63) reported on theisolation of several aromatic components from the essential oil (among themcamphor, borneol), of monoterpenes, and of sesquiterpenes (germacranolides,eudesmanolides, guaianolides, and seco-guaianolides). Ruiz-Cancino et al (64)isolated further sesquiterpenoids (especially of the eudesmanolide type) andtwo flavonoids (eupatilin and jaceosidin). The ethanolic extraction is a potentinhibitor of the antiinflammatory transcription factor NF-κB (15a, b).

ARTEMISIA ABROTANUM Four flavonols isolated fromArtemisia abrotanumre-portedly possess spasmolytic activity. These flavonols show a dose-dependentrelaxing effect on the carbacholine-induced contraction of the guinea-pig tra-chea (65, 66) (Figure 6, Table 1).

ARTEMISIA HERBA-ALBA Artemisia herba-albais widely used for the treatmentof diabetes mellitus. The compound alloxan is used to produce a hypoglycemicstate in experimental animals. Rabbits were fed daily plant aqueous extract(0.39 g/kg) for 2–4 weeks (67), and similar experiments were conducted usingmale adult Wistar rats (68). The results were similar for both rats and rab-bits: (a) protection against body weight loss; (b) maximum reduction in theblood glucose level; (c) a decrease in the elevated serum cholesterol, triglyc-eride, and phospholipids level; and (d ) a reduction of the elevated glycosylatedhemoglobin level.

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Figure 6 Four flavonols isolated fromArtemisia abrotanum.

Extract of the aerial parts of the plant seems to have minimal adverse effectswith a high LD50 value. The LD50 graded doses of the aqueous extract wereadministered intraperitoneally to mice (n = 6, albino mice, 25–30 g). TheLD50 value was observed at 4.49 g/kg body weight, which represents 20.54 gof the crude powdered aerial parts material per l kg body weight (68).

Table 1 The EC50values of four flavonols isolated fromArtemisia abrotanum

Compound EC50 (mM)

1 302 203 254 Significantly lower and only 22% relaxation

was observed at the maximum dose added(48 mM)

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552 HEINRICH ET AL

Table 2 The muscle relaxant effects of 7-O-methylinodictyol

Smooth Muscle EC50 (M)

Ileum 5.6± 0.8× 10−5

Trachea 5.0± 1.7× 10−3

Pulmonary artery 7.3± 1.7× 10−5

Urinary bladder 3.5± 1.1× 10−5

Uterus 2.9± 1.1× 10−5

ARTEMISIA VERLOTORUM Water-alcoholic extract showed a protective effectagainst experimental convulsions elicited by various agents, as well as analgesicand hypothermic actions.Artemisia verlotorumis used as an anticonvulsantand analgesic. High doses (2 g/kg) prevented the onset of electroshock (75 mA,60 Hz) and pentylenetretazole-induced (75 mg/kg, i.p.) convulsions when usingmale Swiss adult albino mice (weighing 25–30 g) (69).

Following i.p. acute administration of the plant extract (0.3 to 8.0 g/kg), theanimals showed reduced locomotor activity. Although no deaths or significantchanges in gross behavior were observed following up to 4 g/kg of the plantextract, all animals given doses higher than 4 g/kg died immediately aftertreatment (69).

ARTEMISIA MONOSPERMA The relaxant effects of 7-O-methyleriodictyol, aflavone isolated from the aerial parts ofArtemisia monosperma, on variousisolated smooth muscle preparations are shown in Table 2.

The inhibition of contraction induced by known therapeutic agents suchas acetylcholine and oxytocin are consistent with the use of this plant in thetreatment of certain gastrointestinal disorders (70) (Figure 7).

Figure 7 7-Methoxy-5,3′,4′-trihydroxy-flavonone.

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ARTEMISIA TRIDENTATA Artemisia tridentatais frequently used as an anthelmin-tic, antiseptic, and analgesic. It is also known as chamiso hediondo (stinkingsagebrush). Many of the compounds identified in this species have notablepharmacological activities, particularly the monoterpenes, SQLs, coumarins,and flavonoids.

SQLs Santonin, a potent anthelmintic, is used to treat ascaridiasis and oxyuri-asis. It acts on the ganglion cells of the worm to induce paralysis so that theparasite can be eliminated via the feces (71). Another SQL with anthelminticproperties is artemisin.

Several monoterpenes found inA. tridentatahave CNS-stimulatory effects(including camphor, cineole, and thujone). Thujone, even when consumed insmall doses, can cause convulsions and death as a result of its psychomimeticeffects (71).

Flavonoids Flavones are known to function by at least four physiologicalmechanisms. They can bind to enzymes and cell membranes and complexheavy metal ions, participate in the electron transfer of enzyme systems, andexhibit free radical scavenging activity (71). The antiinflammatory activityof A. tridentatamay result from the flavones present (luteolin, quercetin, andkaempferol).

Coumarins Scoparone exerts some antihypertensive activity through a possi-ble inhibition of cAMP-phosphodiesterase. Van Sumere & Lea (71) reported a28 to 80 mmHg decrease in blood pressure in dogs when treated with scoparone(cf 72).

BaccharisBaccharisis a large, strictly American genus with approximately 350 species.Only a few are important medicinal plants, and their uses seem to be ratherdiverse (4). Some of the principal medicinal species are discussed below.

BACCHARIS CONFERTA In the region of Veracruz, Mexico,Baccharis confertais used to treat stomach aches (7, 72a) and has been identified in the work ofHernandez (50, p. 59) as quauhizquiztli. It is also recommended for strength-ening mothers after birth, for using as a laxative, for stimulating urination, andfor topically treating baldness and insect bites.

BACCHARIS GLUTINOSA According to Hernandez (50, p. 6), axixtlacotl wasused as a diuretic, against fevers, as a diaphoretic, and to remove blotches fromthe face. Tea made from the leaves is taken to lose weight and as a contraceptive.The tea is also used to stop blood loss after giving birth. The leaves, heatedover coals, are placed on the head as a remedy for headache or on a sore areaof the body (8, p. 422; 73, p. 664).

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554 HEINRICH ET AL

BACCHARIS SALICIFOLIA The green leaves/leafy branches ofBaccharis salici-folia are applied externally as a remedy for inflammation, diarrhea, and dysen-tery.

BACCHARIS SAATHROIDESA tea made by boiling the twigs ofBaccharis saath-roidesis taken as a remedy for colds. The same tea is rubbed on sore musclesfor relief (8).

BACCHARIS SERRAEFOLIABaccharis serraefoliais a popular form of treatmentfor various gastrointestinal illnesses with the Tzeltal and Tzotzil of Chiapas(72a).

BACCHARIS MULTIFLORA, BACCHARISSPP. An infusion prepared from the leavesof Baccharis multiflora, Baccharisspp. is said to be effective against catarrhsand was used for urinary problems in nineteenth century Mexico (53, pp. 165–66; 73). Two unidentified species of this genus—quappatli and malinalli—arelisted in the Florentine Codex (49, pp. 142 and 144) as treatments for blotchedface (applied internally) and for worms in the eyes and crab lice in the eyelids(especially applied externally), respectively.

BACCHARIS TRINERVIS Baccharis trinervisis used by the Huastec in the treat-ment of high fever, edema, sores, and muscle cramps. It is also applied inthe case of dizziness and lack of blood. The Huastec regard it as effective ifone feels sleepy and if there is insufficient milk production (9, pp. 553–54).In Veracruz, a preparation made from the leaves is used for the treatment oftyphoid fever (7, p. 21). Berlin & Berlin (72b) list it as one of the most popularTzeltal and Tzotzil remedies for gastrointestinal disorders.

BACCHARIS VACCINOIDES Berlin & Berlin (72b) mentionsBaccharis vacci-noidesas one of the most popular remedies from Chiapas for gastrointestinaldisorders.

PHYTOCHEMISTRY B. salicifolia is rich in essential oil–containing monoter-penes (alpha-phellandrene is the main component), sesquiterpenes (with ger-macrene D, bicyclogermacrene and delta-cadiene as the main products), andnumerous monooxygenated sesquiterpenes (74). Typical for the genus are alsogermacrene-type sesquiterpenoids, diterpenes, clerodanes, and labdanes (74).

PHARMACOLOGY Baccharis gaudichaudianais mainly used as a treatmentfor diabetes, but other uses have been noted (75). Three new diterpenoids—gaudichaudol C (1), gaudichaudone (2), and articulin acetate (3)—isolated fromB. gaudichaudiana, exhibited significant cytotoxic activity against certain can-cer cell lines (75) (Figure 8).

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Figure 8 Three new diterpenoids: gaudichaudol C (1), gaudichaudone (2), and articulin acetate(3).

Gaudichaufol C (1) demonstrated significant activity against P388 with ef-fective dose (ED50) of 2.4 mg/ml. It also showed an ED50of 4.7 mg/ml against amulti-drug resistant KB-V1 cell line. Gaudichaudone (2) was found to be inac-tive with all the epithelial cell types tested and weakly active against P388 cells(ED50 11.7 mg/ml). However, articulin acetate (3) showed a greater activityagainst P-388 cells (ED50 1.7 mg/ml) (75).

Antiinflammatory Three different species of the genusBaccharis—crispa,trimera, andarticulata—were tested for antiinflammatory activity. These plantsare used in traditional medicine for the treatment of rheumatism, liver diseases,wounds, and ulcers (75). The aqueous extract was tested at a single dose of100 mg/kg using female Wistar rats (130–160 g). To assess the antiinflammatoryeffect, the carrageenan-induced foot edema test was performed. TheB. trimeraextract, administered intraperitoneally, produced a significant inhibition ofedema. However,B. articulataandB. crispaonly showed a weak or nonsignifi-cant effect. None of the aqueous extracts were active when administered orally.

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556 HEINRICH ET AL

Antispasmodics Leaves ofB. salicifolia, B. serraefolia, B. trinervis, andB.vaccinioideswere active in electrically induced contraction of the guinea-pigileum. The inhibition was tested in three concentrations (62, 125 and 250µg)and B. serraefoliashowed the largest inhibition of contraction of the fourspecies, 44 and 43%, respectively, for three different samples. The stemsof these species were generally inactive (76).

Bactericidal The extract ofB. glutinosais active againstStaphylococcus au-reus, Bacillus subtilis, andStreptococcus faecalis(77).

ElephantopusThis tropical genus is particularly well known because one species,Elphantopusscaber, is now a widely distributed bad herb in many countries. There areapproximately one dozen species of these herbaceous perennials in North andSouth America.

ELEPHANTOPUS SPICATUS[SYN.: PSEUDELEPHANTOPUS SPICATUSC.F. BAKER, VER-

NONIEAE] Ethnobotany The leaves ofElephantopus spicatusare used forthe treatment of cough and headache (9, p. 635). Applied topically, they areemployed as an antipyretic, for the treatment of erysipelas, skin infections, andmeasles. A preparation made from the roots is taken as a remedy for colic;the whole plant helps against diarrhea (7, p. 86). It is one of the most popularcough remedies of middle America (54, p. 961).

Pharmacology E. scaberhas been used to cause diuresis and antipyresis andto eliminate bladder stones. This genus has been reported to contain the hydrox-ylated germacranolides molephantin and molephantinin, which also possess cy-totoxic and antitumor properties (79–81). This plant also contains phantominand itscis-epoxide, which have been reported to exhibit potent inhibitory ac-tions on Ehrlich ascites carcinoma and on Walker 256 carcinosarcoma cells(80, 81).

Pharmacological experiments on the plant extract were conducted by Poli et al(82). Oral administration (30, 60, 100, 300, and 600 mg/kg) and i.p. injection(3, 10, and 30 mg/kg) failed to modify the reaction time in the hot-plate test.

Intraperitoneal injection (300 and 600 mg/kg) in adult male Wistar rats sig-nificantly reduced brewer’s yeast–induced hyperthermia 1, 2, and 3 h afteradministration of both extracts. However, oral administration of both extracts(300 and 600 mg/kg) failed to reduce edema induced by carrageenan in the rathind paw at 1, 2, and 4 h following exposure.

In addition, the aqueous (300 and 600 mg/kg, p.o.) extract significantly de-creased intestinal transit in mice. The ethanolic extract, up to 6 g/kg, didnot produce significant modifications in the behavior of mice. Intraperitoneal

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injection of both aqueous (0.03–3.0 g/kg) and alcoholic (0.1–3.0 g/kg) extractsinduced writhing, loss of muscle tone, ataxia, prostration, and death. The es-timated LD50 in adult male Swiss Webster mice was greater than 2 g/kg i.p.and after oral administration was greater than 6 g/kg. These acute toxicityexperiments reveal a low toxicity for the plant extract (83).

HeleniumETHNOBOTANY This American genus has yielded several ornamental plants(e.g.Helenium autumnale) but is also known for its toxic effects on herbivores.TheHeleniumgenus contains about 40 species of annual and perennial herbs.

Helenium mexicanum (syn.: Gomphrena decumbens, Heliantheae)/Sneezeweed(Engl.)/Ueuei itzontecon (Nahuatl) Helenium mexicanumis taken orally if aperson is very sick or to treat a stomach ache, faint heart beat, throbbing temples,quivering nerves, fever, or pus in the genital organ (49, p. 170).

Helenium quadridentatumdel Amo (7, p. 105) lists the following uses forHelenium quadridentatum: treatment of fever, catarrh, and testicular inflam-mations and as a diuretic and insecticidal. Martinez (53, p. 430) mentions theplant as a means to provoke sneezing, as a diuretic, and as a treatment of colicand fever.

CHEMISTRY AND PHARMACOLOGY SQLs isolated fromH. autumnale, such ashelenalin, mentioned earlier, possess cardiotonic properties and also exhibitantiinflammatory, hypolipidemic, antibacterial, and antitumor activity. Thelikely antitumor mechanism of helenalin is a marked potentiation of the in-crease in intracellular free [Ca2+] concentration produced by mitogens such asvasopressin, bradykinin, and platelet-derived growth factor in Swiss mouse 3T3fibroblasts. The concentrations of helenalin used by Powis et al (83) inhibitedcell proliferation. However, at higher concentrations of helenalin, the intra-cellular [Ca+2] was inhibited. Constitutive activation of intracellular signalingpathway by oncogenes can lead to unregulated cell growth in cancer cells. Theeffect of helenalin appears to result from an increase in the uptake of Ca2+

into nonmitochondrial stores and an increase of the extracellular [Ca+2] (83)(Figure 9).

MontanoaMONTANOA TOMENTOSA(HELIANTHEAE)/CIHUAPATLI Most Asteraceae areherbs or little shrubs. The trees of the genusMontanoa(tree daisy) thereforestand out as very unusual plants. They also are very showy during the floweringseason. But the genus also includes one of the most important medicinal plantsof Mexico: Montanoa tomentosa(4).

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558 HEINRICH ET AL

Figure 9 Structure of helenalin.

Ethnobotany The Azteccihuapatlior modernzoapatleis the species of theAsteraceae that has received the most attention in recent pharmacological andpharmaceutical research (84, pp. 193–223). The plant is and was used as amedicine to speed up labor and also to induce abortion. The literal translationof the two words of the namecihuatlandpatli is woman and remedy/medicine,respectively. This plant was widely cited as an oxytocic in pre-Columbiantimes (50, 2:294; 49, 6:159; 85, p. 180; 86, p. 89). De la Cruz (52, p. 217)mentions it as part of a complex mixture including quauhalahuac (whose botan-ical identification is still controversial), and the tail of the tlacuatzin (Didelphisspp.), which may itself be oxytocic (87). The herb continued to be used duringcolonial times and is still used widely, particularly in rural areas (7, 88–91).

Pharmacology M. tomentosahas been studied and reported to contain diter-penes that are responsible for its oxytocic properties (84).

PackeraThis small genus is closely related to the genusSencio(ragworts), from which itwas recently separated. ThePackeragenus contains biologically active pyrroliz-idine alkaloids.

PACKERA CANDISSIMA (SENECIONEAE)/GROUNDSEL(ENG.)/LECHUGILLA DE LA

SIERRA, CHUCACA, TE DE MILAGROS(SPAN.) Ethnobotany The whole plantPackera candissimais used as tea for kidney ailments; as a general medicine;and to cure sores, ulcers, and vaginal ailments (59). Similar uses are reportedfor Packera bellidifolia(Kunth.) [WA Weber & A Loeve (in 4) [syn.:Seneciobellidifolius Kunth., Senecio vulnerariaDC.]. At Harvard there is a voucherspecimen from WP Hewitt (in 4) with a report on its use for kidney and bladdertrouble in Mexico. The fresh plant is also ground with olive oil and appliedas a poultice for boils, tumors, and infections (92). The Florentine Codex (47,9:152) has an external use of the powdered iztac palancapatli for abscesses or

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wounds. Martinez (53) reported uses of the plant to wash skin ulcers and totreat syphilis.

Phytochemistry The aerial parts ofP. candidissimayielded four pyrrolizidinealkaloids (PAs): senecionine, integerrimine, retrorsine, and usaramine. Theroots yielded senecionine and integerrimine, as well as senkirkine and twounidentified PAs. The aerial parts have 0.06% alkaloids, the roots 0.33%.Additionally, two furanoerimophilane-type sesquiterpenes were isolated (1).Another species of this genus yielded monoterpene lactones and quinones (93).

Toxicology The users of this traditional herbal preparation are at high risk ofbeing poisoned because of the high content of alkaloids. According to Bah et al(1), the infusion of 1.3 g of the root or 2.7 g of the aerial parts contains enoughpyrrolizidine alkaloids to produce chronic or acute veno-occlusive diseases,especially in children. This amount may also produce acute liver damage.Furthermore, their pyrrole metabolites, produced in the liver, are alkylatingagents and thus have carcinogenic and mutagenic effects. Evaluation using thistraditional remedy orally can certainly not be recommended.

PartheniumPartheniumis a small genus of approximately 16 species of shrubs, herba-ceous perennials and annuals. A well-known species of this genus is guayule(Parthenium argentatum), which is considered an alternative source for rub-ber and which was an emergency rubber during the Second World War. Allspecies of this genus but especiallyParthenium hysterophorusare known tocause severe contact dermatitis (4).

PARTHENIUM HYSTEROPHORUSL. (HELIANTHEAE) SANTA MARIA FEVERFEW

Ethnobotany P. hysterophorusis used medicinally by many indigenous andmestizo groups of Mexico. Villada (94) lists the plant as a remedy for malaria,for neuralgia, and as a vermifuge. It is employed by the Mixe Indians in theform of baths to cure fever and body pain (95), and by the Huastec to treat sores,muscular aches, epilepsy, and fever (see 9 and 53 for similar uses from otherareas).

Phytochemistry The species is rich in SQLs; parthenin is the main compound(96).

Pharmacology Parthenin, the main SQL ofP. hysterophorus, was shown topossess in vitro and in vivo (hepatic amoebiasis in hamsters) amoebicidal ac-tivity. The MIC50 in vitro is 10–12µg/ml, a value comparable to that ofmetronidazole; however, in vivo parthenin (ED50 40 mg/kg) was less effectivethan metronidazole. Also, the compound was shown to be quite toxic (96).

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Toxicology In hamsters, a 40 mg/kg dose proved toxic to two out of sevenanimals. The LD50 and MLD doses in mice were established as 450 and 600mg/kg, respectively (96). The plant has now become a pantropical pest and astrong elicitor of allergic contact dermatitis (97).

TithoniaTithonia is a small genus of less than 10 species. The Mexican and CentralAmerican genusTithonia has yielded some ornamental plants (e.g.Tithoniarotundifolia), and at least one species,Tithonia diversifolia, is now a pantropi-cally distributed bad weed.

TITHONIA DIVERSIFOLIA(HEMSL.) A. GRAY. (HELIANTHEAE)/WILD ARNICA (ENGL.)/

ARNICA DE LA MONTANA, ARNICA (SPAN.) Ethnobotany T. diversifoliaisone of the most frequently seen plants in gardens of the tropical areas of Mexicoand seems to be an important, but ethnobotanically little known, medicinal plantin these regions. With the Lowland Mixe it is used orally to treat malaria andother forms of fever and topically to treat hematomas and muscular cramps(95). Morton (54) also cites its use as a liniment from Yucatan. These usesmay result from the similarity of the flower heads of this species to the onesof European arnica (Arnica montanaL.). This assumption is corroborated byits popular names: Arnica de la montana and arnica (54, 95). Berlin & Berlin(72b) list it as an important remedy for gastrointestinal complaints. del Amo (7)cites it as an antiinflammatory and as treatment for wounds and skin eruptions(72a).

Phytochemistry The genus is rich in SQLs. A large number of other SQLshave been found, especially forT. diversifolia(98, 99). Tirotundin and manyof the other SQLs isolated from this species are interesting phytochemically inthat they contain several epoxides (100).

Pharmacology The aerial parts ofT. diversifolia, which is also used in the pop-ular medicine of Taiwan, showed antiinflammatory effect in the carrageenan-induced rat paw edema test. Treatment with the water extract (1000 mg/kg)decreased the paw edema at a statistically significant level (101). The ethanolicextract is a potent inhibitor of the transcription factor NFκB (15a). An ethano-lic extract from the aerial part showed no antimalarial effect (95) but did havesome antipyretic action (YH Kim, personal communication).

CONCLUSION

In this review, we discussed aspects of recent reports of the pharmacology andtoxicology of plant extracts and recently identified chemicals from the plantfamily Asteraceae used by Mexicans and Mexican Americans/Chicanos. The

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number of plant species of this family in Mexico and the Southwest is in thethousands, and each species undoubtedly contains hundreds of untested com-pounds with biological activity. It is impossible at this point to list all of theseactivities; instead, we reviewed the most widely used Mexican and MexicanAmerican herbal remedies to give medical practitioners some idea of the pos-sible physiological effects of the herbal remedies used by their patients and toraise a warning flag whenever potential hazardous risks are present. The capac-ity of many of the natural products of the Asteraceae to form adducts with GSHand either stimulate or inhibit the cytochrome P-450–mediated metabolism ofxenobiotics is particularly relevant to medical practitioners, as these effects mayprofoundly change the physiological effects of the drugs they are prescribingfor their patients.

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Literature Cited

1. Bah M, Bye R, Pereda-Miranda M. 1994.Hepatotoxic pyrrolizidine alkaloids in theMexican medicinal plantPackera can-ditissima (Asteraceae: Senecioneae).J.Ethnopharmacol.43:19–30

2. Moerman DE. 1991. The medicinal floraof native North America—an analysis.J.Ethnopharmacol.31:1–42

3. Font Quer P. 1962.El Dioscorides Reno-vado. Barcelona: Lobar

4. Heinrich M. 1996. Ethnobotany of Mex-ican Compositae: an analysis of histori-cal and modern sources.Proc. Int. Com-positae Conf., Kew, 1994, Ser. ed. DJNHind. Biology and Utilization, Vol. ed.PDS Caligaria, DJN Hind, 2:475–503.Kew, UK: R. Botanic Gardens

5. Heinrich M, Antonio Barrera N, KuhntM. 1992. Arzneipflanzen in Mexiko: DerMarkt von Matias Romero (Oaxaca).Deutsche Apothekerzeitung.132:351–58

6. Heinrich M, Rimpler H, Antonio BarreraN. 1992. Indigenous phytotherapy of gas-trointestinal disorders in a Mixe Lowlandcommunity.J. Ethnopharmacol.36:63–80

7. del Amo RS. 1979.Plantas medicinalesdel Estado de Veracruz. Xalapa, Veracruz:Inst. Nacl. Invest. sobre Recursos Bioticos

8. Felger RS, Moser MB. 1974. Seri Indianpharmacopoeia.Econ. Bot.28:414–36

9. Alcorn JB. 1984.Huastec Mayan Ethnob-otany. Austin, TX: Univ. Texas Press. 982pp.

10. Rodriguez E, Towers GHN, Mitchell JC.1976. Biological activities of sesquiter-pene lactones.Phytochemistry15:1573–80

11. Fischer NH, Olivier EJ, Fischer HD.1979. The biogenesis and chemistry ofsesquiterpene lactones. InFortschritt derChemie organischer Naturstoffe, ed. WHerz, H Grisebach, GW Kirby, pp. 47–390. Wien/New York: Springer-Verlag

12. Seaman FC. 1982. Sesquiterpene lactonesas taxonomic characters in the Aster-aceae.Bot. Rev.48:121

13. Picman AK. 1986. Formation of parth-enin and related sequiterpene lactoneswith cysteine and glutathione.Biochem.Syst. Ecol.14:255–81

14. Stuppner H, Rodriguez E. 1987. Isola-tion, purification of major sequiterpenelactones.Phytochem. Bull.19:28–38

15. Lee K, Hall IH. 1977. Synthesis andantitumor activity of uracil and thyminealpha-methylene-gamma lactones and re-lated derivatives.J. Med. Chem.20:911–14

15a. Bork PM, Schmitz ML, Weimann C,Kist M, Heinrich M. 1996. Nahua Indianmedicinal plants (Mexico): inhibitoryactivity of NF-κB as an antiinflamma-tory model and antibacterial effects.Phy-tomedicine3(2):263–69

15b. Bork PM, Schmitz ML, Kuhnt M, EscherC, Heinrich M. 1997. Sequiterpene lac-tone containing Mexican Indian medici-

Ann

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harm

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. Tox

icol

. 199

8.38

:539

-565

. Dow

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562 HEINRICH ET AL

nal plants and pure sesquiterpene lactonesas potent inhibitors of transcription factorκB (NF-κB). FEBS Lett.402:85–90

15c. Hehner SP, Heinrich M, Bork PM, VogtM, Ratter F, et al. 1998. Sequiterpene lac-tones specifically inhibit a common stepof NF-κB activation by preventing thedegredation of IκB-α. J. Biol. Chem.Inpress

16. Kupchan SM, Eakin MA, Thomas AM.1971. Tumor inhibition: structure cyto-toxicity relationships among the sequiter-pene lactones.J. Med. Chem.14:1147

17. Mew D, Balza F, Towers GHN, Levy JG.1982. Anti-tumor effects of the sequiter-pene lactone Parthenin.Planta Med.45:23–27

18. Hladon B, Chodera A. 1975. Sequiter-pene lactones: cytostatic and pharmaco-logical activity.Arch. Immunol. Ther. Exp.23:857–65

19. Woerdenbag HJ, Lemstra J, Hendricks H,Malingre TM, Konings AWT. 1987. In-vestigation of the anti-tumor action of eu-patoriopicrin.Planta Med.53:318–22

20. Giordano OS, Guerreiro E, PestchankerMJ Guzman Y, Pastor D, Guarolia T.1990. The gastric cytoprotective effectof several sequiterpene lactones.J. Nat.Prod.53:803–9

21. Giordano OS, Pestchanker MJ, Guer-reiro E, Saad JR, Enriz RD, et al.1992. Structure-activity relationship inthe gastric cytoprotective effect of sev-eral sequiterpene lactones.J. Med. Chem.35:2452–58

22. Ivie GW, Witzel DA. 1983. Sesquiterpenelactones: structure, biological action andtoxicological significance. InHandbookof Natural Toxins, ed. RF Keeler, AT Tu,pp. 534–84. New York: Academic

23. Stevens KL, Riopelle RJ, Wong RY.1990. Repin, a sequiterpene lactone fromAcroptilon repenspossessing exceptionalbiological activity.J. Nat. Prod.53:218–21

24. Stevens KL, Riopelle J. 1993. Bioac-tive natural products, detection, isolation,and structural determination. InIn VitroNeurotoxicity Bioassay: Neurotoxicity ofSesquiterpene Lactones, ed. S Colegate.Boca Raton, FL: CRC

25. Wang Y, Hamburger M, Cheng CHK,Costall B, Hostettmann K. 1991. Neu-rotoxic sequiterpenoids from the Yel-low Star ThistleCentaurea solstitialisL.(Asteraceae). Helv. Chim. Act.74:117–23

26. Robles M, Wang N, Kim R, Choi BH.1997. Cytotoxic effects of repin, a princi-pal sequiterpene lactone of Russian knap-weed.J. Neurosci. Res.47:90–97

27. Robles M, Aregullin M, West J, Ro-driguez E. 1995. Recent studies on thezoopharmacognosy, pharmacology andneurotoxicology of sequiterpene lactones.Planta Med.61:199–203

28. Warren RG. 1986. Feverfew partheno-lides.Aust. J. Pharm.67:475

29. Heptinstall S. 1988. Feverfew—an an-cient remedy for modern times.J. R. Soc.Med.81:373

30. Hobb C. 1989. Anti-migraine prophy-laxis.Herbal Gram20:26

31. Awang DVC. 1989. Parthenolide contentand bioactivity of feverfew.Can. Pharm.J. 122:266

32. Heptinstall S, White A, Williamson L,Mitchell JRA. 1985. Extracts of fever-few inhibit granule secretion in bloodplatelets and polymorphonuclear leuco-cytes.Lancet1(843):1071–74

33. Pugh WJ, Sambo K. 1989. Prosta-glandin synthetase inhibitors in feverfew.J. Pharm. Pharmacol.40:743–45

34. Johnson ES, Kadam NP, Hylands DM,Hylands PJ. 1985. Efficacy of feverfewas prophylactic treatment of migraine.Br.J. Med.291:569–73

35. Murphy JJ, Heptinstall S, Mitchell JRA.1988. Randomized double-blind placebocontrolled trial of feverfew in migraineprevention.Lancet2(8604):189–92

36. Fisher AA. 1996. Esoteric contact der-matitis, part IV: devastating contact der-matitis in India produced by Americanparthenium weed (the scourge of India).CUTIS5:297–98

37. Sriramarao P, Prakash O, Metcalf DD,Rao PV. 1993. The use of murine poly-clonal anti-ideotypic antibodies as surro-gate allergens in the diagnosis of Parthe-nium hypersensitivity.J. Allergy Clin.Immunol.92:567–80

38. Gupta N, Sriramarao P, Kori R, RaoPV. 1995. Immunochemical characteriza-tion of rapid and slowly released aller-gens from the pollen ofParthenium hys-terophorus. Int. Arch. Allergy Immunol.107:557–65

39. Sriramarao P, Rao PV. 1993. Allergeniccross reactivity between Parthenium andragweed pollen allergens.Int. Arch. Al-lergy Immunol.100:79–85

40. Mattocks AR. 1986.Chemistry andToxicology of Pyrrolizidine Alkaloids.London: Academic. pp. 158–271

41. Rodriguez E, Aregullin M, Nishida T, Ue-hara S, Wrangham R, et al. 1985. Thiaru-bine A, a bioactive constituent ofAspilia(Asteraceae) consumed by wild chim-panzees.Experientia41:419–20

Ann

u. R

ev. P

harm

acol

. Tox

icol

. 199

8.38

:539

-565

. Dow

nloa

ded

from

ww

w.a

nnua

lrev

iew

s.or

gby

Way

ne S

tate

Uni

vers

ity o

n 09

/17/

11. F

or p

erso

nal u

se o

nly.




42. Kim H, Lee YH, Kim SI. 1988.Korean J.Toxicol.4:95–105

43. Hansen L, Boll PM. 1986. The poly-acetylenic falcarinol as the major allergenin Schefflera arboricola. Phytochemistry25:529–30

44. Muir AD, Cole ALS, Walker JRL. 1978.Antibiotic compounds from New Zealandplants.Planta Med.44:232–36

45. Kemp MS. 1978. Falcarinol: an anti-fungal polyacetylene fromAegopodiumpodagraria. Phytochemistry17:1002

46. Baba K, Tabota Y, Kozawa M, Kimina Y,Arichi S. 1987. Studies on Chinese tradi-tional medicine Fang-Feng.ShoyakugakuZasshi41:189–94

47. Teng CM, Kuo SC, Ko FN, Lee JC,Lee LG, et al. 1989. Antiplatelet actionsof panaxyone and guisenosides isolatedfrom ginseng.Biochem. Biophys. Acta990:315–20

48. Lee KD, Huemer RP. 1971. Antitumoralactivity of Panax ginseng extracts.Jpn. J.Pharmacol.21:299–302

48a. Hansel R, Keller K, Rimpler H, Schnei-der G, eds. 1994.Hagers Handbuch derPharmazeutischen Praxis. Drogen A-D,pp. 45–54. Heidelberg: Springer-Verlag

49. de Sahagun B. 1906.Codice Matritensedel Real Palacio, ed. F del Paso y Tron-coso. Madrid: Hauser & Manet

50. Hernandez F. 1959–1960.Historia Nat-ural de Nueva Espana, ed. G SomolinosD’Ardois. Mexico D.F.: UNAM. Vols. 2and 3.

51. Hernandez Fr. 1984.Comentarios a laobra de Francisco Hernandez. MexicoD.F.: UNAM. Vol. 7

52. De la Cruz M. 1991(1552).LibellusMedicinallibus Indorum Herbis. MexicoD.F: Fondo Cult. Econ./Inst. Mexicano deSeguro Social. 2 Vols, 64 Folios, 258 pp.

53. Martinez M. 1969.Las Plantas Medici-nales de Mexico. Mexico D.F.: Botas. 657pp. 5th ed.

54. Morton J. 1981.Atlas of Medicinal Plantsof Middle America, Bahamas to Yucatan.Springfield, IL: Thomas. 420 pp.

55. Tozyo T, Yoshimura Y, Sakurai K, UchidaN, Takeda Y, et al. 1994. Novel antitumorsequiterpenoids inAchillea millefolium.Chem. Pharm. Bull.42:1096–100

56. Muller-Jakic B, Breu W, Pröbstle A,Redl K, Greger H, Bauer R. 1994. Invitro inhibition of cyclooxygenase and5-lipoxygenase by Alexanides from Echi-nacea and Adrillea species.Planta Med.60:37–40

57. Mustafa EH, Abu Zarga M, Abdalla S.1992. Effects of cirsiliol, a flavone iso-lated fromAchillea fragantissimaon rat

isolated ileum.Gen. Pharmacol.23:555–60

58. Ruiz Salazar C. 1989.Contribucion alestudio de las plantas medicinales delas Delegacion Xochimilco. PhD thesis.Mexico D.F. MEXU, Herbario Nacional(UNAM)

59. Bye R. 1986. Medicinal plants of theSierra Madre: comparative study ofTarahumara and Mexican market plants.Econ. Bot.40:103–24

60. Linares ME, Bye R, Flores P. 1990.Tes curativos de México. Mexico D.F.:UNAM. Cuadernos Inst. Biol. No. 7. 140pp.

61. Rivera MI. 1943. Algunas plantas medic-inales de Izucar De Matamoros y pueblosanexos.Anal. Inst. Biol.14(l):37–67

62. Pimentel Tort JA. 1988. Plantas de usomedicinal entre los bosques de Tecpatón.Tuxtla Gutierrez, Chiapas: Inst. Chia-paneco cult. 51 pp.

63. Jakupovic J, Tan RX, Bohlmann F, BoldtPE, Jia ZJ. 1991. Sesquiterpene lactonesfrom Artemisia ludoviciana. Phytochem-istry 30(5):1573–77

64. Ruiz-Cancino A, Cano AE, Delgado G.1993. Sesquiterpene lactones and flavo-noids from Artemisia ludoviciana ssp.mexicana. Phytochemistry33(5):1113–15

65. Marles RY, Kaminski Y, Arnason JT,Pazos-Sanou L, Fischer NH, et al. 1992.A bioassay for inhibition of serotonin re-lease from bovine platelets.J. Nat. Prod.55:1044–56

66. Bergendorf O, Sterner O. 1995. Spas-molytic flavonols fromArtemisia abrot-anum. Planta Med.61:370–71

67. Al-Shamaony L, Al-Khazraji SM, TwaijHA. 1994. Hypoglycemic effect ofArt-emisia herba-alba. II. Effect of a valu-able extract on some blood parametersin diabetic animals.J. Ethnopharmacol.43:167–71

68. Al-Shamaony L, Al-Khazraji SM, TwaijHA. 1993. Hypoglycemic effect ofArte-misia herba-alba. I. Effect of differentparts and influence of the solvent on hy-poglycemic activity.J. Ethnopharmacol.40:163–66

69. de Lima TCM, Morato GS, TakahashiRN. 1993. Evaluation of the central prop-erties of Artemisia verlotorum. PlantaMed.59:326–29

70. Abu-Niaaj L, Abu-Zarga M, Sabri S,Abdalla S. 1993. Isolation and biolog-ical effects of 7-O-methyleniodictyol,a flavonone isolated fromArtemisiamonosperma, on rat isolated smooth mus-cles.Planta Med.59:42–45

Ann

u. R

ev. P

harm

acol

. Tox

icol

. 199

8.38

:539

-565

. Dow

nloa

ded

from

ww

w.a

nnua

lrev

iew

s.or

gby

Way

ne S

tate

Uni

vers

ity o

n 09

/17/

11. F

or p

erso

nal u

se o

nly.



564 HEINRICH ET AL

71. Van Sumere CF, Lea PJ. 1985. The bio-chemistry of plant phenolics.Annu. Proc.Phytochem. Soc. Eur., Oxford, England:Clarendon

72. Kelley BD, Appelt JM, Appelt GD. 1992.Artemisia tridentata(sagebrush) in theSouthwestern USA: medicinal uses andpharmacological implications.Int. J. Ad-dict. 27:347–66

72a. Weimann C, Heinrich M. 1997. Indige-nous medicinal plants in Mexico: the ex-ample of Nahua (Sierra de Zonglicia).Bot. Acta11:62–72

72b. Berlin EA, Berlin B. 1996.Medical Eth-nobotany of the Highland Maya of Chia-pas, Mexico. Princeton: Princeton Univ.Press

73. Dragendorff G. 1967. (1898).Die Heilp-flanzen der verschiedenen Voelker undZeiten. Muenchen: Fritsch. 855 pp.

74. LoZayza I, Abujder D, Aranda R,Jakupovic J, Collin G, et al. 1995. Essen-tial oil of Baccharis salicifolia, B. lati-folia andB. dracunculifolia. Phytochem-istry 38:382–89

75. Kinghorn D, Fullas T, Hussain KA, ChaiHB, Pezzuto JM, et al. 1994. Cytotoxicconstituents ofBaccharis guadichaudi-ana. J. Nat. Prod.57:801–7

76. Tortoriello J, Meckes-Fischer M, Vil-lareal ML, Berlin B, Berlin E. 1995. Spas-molytic activity of medicinal plants usedto treat gastrointestinal and respiratorydiseases in the highland Chiapas.Phy-tomedicine2(l):57–66

77. Dimayuga RE, Garcia SK. 1991. An-timicrobial screening of medicinal plantsfrom Baja California Sur, México. J.Ethnopharmacol.31:181–92

78. Lee KH, Furukawa H, Kozuka M, HuangHC, McPhail AT, et al. 1973. Mole-phantin, a novel cytotoxic germacranolidefrom Elephantopus mollis. J. Chem. Soc.Chem. Commun.14:476–77

79. Lee KH, Ibuka T, Huang HC. 1975.Antitumor agents: molephantin, a newpotent antitumor sesquiterpene lactonefrom Elephantopus mollis. J. Pharm. Sci.64:1077–78

80. McPhail AT, Onan KD, Gross PM. 1974.Structure and sterochemistry of the epox-ide of phantomolin, a novel cytotoxicsequiterpene lactone fromElephantopusmollis. Tetrahedron Lett.32:2739–41

81. Lee KH, Imakura Y, Sims D, Wu RY, HallIH, et al. 1980. Antitumor agents: struc-tural elucidation of sequiterpene lactonesmicrohelenins-A, -B, and -C, microleninacetate, and plenolin fromHelenium mi-crocephalum. J. Pharm. Sci.69:1050–56

82. Poli A, Nicodau M, Siñoes CMO,

Ribeiro-do-Valle Nicolau RM, Zanin M,et al. 1992. Preliminary pharmacologicevaluation of crude whole plant extractsof Elephantopus scaber. Part I: in vivostudies.J. Ethnopharmacol.37:71–76

83. Powis G, Gallegos A, Abraham RT,Ashendel CL, Zalkow LH, et al. 1994.Increased intracellular Ca2+ signallingcaused by the antitumor agent helenalinand its analogs.Cancer Chemother. Phar-macol.34:344–50

84. Lozoya X, Lozoya M. 1982.Flora medic-inal de Mexico, primera parte: plantasindigenas. Mexico, DF, Mexico: Inst.Mexicano Seguro Social

85. de Sahagun B. 1963. Earthly things.Codice Matritense del Real Palacio, ed.F del Paso y Troncoso. Madrid: Hauser& Manet. Book II. 397 pp.

86. de Pomar JB. 1964. Relacion. InPoe-sia Nahuatl, ed. AM Garibay, 1:149–219.Mexico, DF, Mexico: UNAM

87. Ortiz de Montellano B. 1990.AztecMedicine, Health and Nutrition. NewBrunswick, NJ: Rutgers Univ. Press

88. Lewis O. 1970.Life in a Mexican Village.Tepoztlan Revisited. Urbana: Univ. Illi-nois Press

89. Quiroz-Rodiles A. 1945. Breve historia dela obstetricia en Mexico.Obstet. Ginecol.Latino-Am.3:77–92

90. Ortiz de Montellano BR, Browner C.H.1985. Chemical bases for medical plantuses in Oaxaca, Mexico.J. Ethnophar-macol.13:57–88

91. Baytelman B. 1979.Etnobotanica en elestado de Morelos. Cuernavaca (México):Inst. Nacl. Antropol. Hist., Centro Re-gional de Morelos. 287 pp.

92. Reis A, Siri V. 1973.Drugs and Foodsfrom Little-Known Plants. Notes on Har-vard University Herbaria. Cambridge,MA: Harvard Univ. Press. 363 pp.

93. Bohlmann F, Zdero C, King RM,Robinson H. 1981. The first Acete-lenic Monoterpene and other constituentsfromSenecio clevelandii. Phytochemistry20:2425–27

94. Villada MM. 1888. Apuntos acerca deplantas de la familia de las compuestasempleadas en la medicina.Gaceta Med.Mexico23:147–55

95. Heinrich M. 1989. Ethnobotanik derTieflandmixe (Oaxaca, Mexico) und phy-tochemisch Untersuchung von Caprariabiflora L. (Scrophulariaceae).PhD the-sis. Berlin/Stuttgart: J. Cramer in Gebr.Borntraeger Verlagsbuchhdlg.

96. Sharma GL, Bhutani KK. 1988. Plantbased antiamoebic drugs, part 2.PlantaMed.54:120–22

Ann

u. R

ev. P

harm

acol

. Tox

icol

. 199

8.38

:539

-565

. Dow

nloa

ded

from

ww

w.a

nnua

lrev

iew

s.or

gby

Way

ne S

tate

Uni

vers

ity o

n 09

/17/

11. F

or p

erso

nal u

se o

nly.




97. Wedner HJ, Zenger VE, Lewis WH. 1987.Allergic reactivity of Parthenium hys-terophorus (Santa Majo Feverfew) pollen:an unrecognized allergen.Int. Arch. Al-lergy Appl. Immunol.84:116–22

98. Calzada JG, Ciccio JF. 1978. Aislamientode Tirotundina a partir de Tithonia diver-sifolia (Hemsl.) Gray.Rev. Latinoamer.Quim.9:202–3

99. Schuster A, Stokes S, Papastergiou F,Castro V, Poveda L, Jakupovic J. 1992.

Sesquiterpene lactones from two Tithoniaspecies.Phytochemistry31:3139–43

100. Baruah NC, Sharma RP, MadhusudananKP, Thyagarajan G. 1979. Sesquiterpenelactones ofTithonia diversifolia. J. Org.Chem.44:1831–35

101. Lin CC, Lin ML, Lin JM. 1993. The an-tiinflammatory and liver protective effectof Tithonia diversifolia(Hemsl.) Cray andDicliptera chinensisJuss. extracts in rats.Phytother. Res.7:305–9

Ann

u. R

ev. P

harm

acol

. Tox

icol

. 199

8.38

:539

-565

. Dow

nloa

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