ANIMAL BEHAVIOUR, 2005, 70, 975–989doi:10.1016/j.anbehav.2005.03.005

REVIEW

The evolution of herbal medicine: behavioural perspectives

BENJAMIN L. HART

School of Veterinary Medicine, University of California, Davis

(Received 12 December 2003; initial acceptance 13 February 2004;

final acceptance 7 March 2005; published online 3 October 2005; MS. number: ARV-27R)

The current popularity of traditional herbal supplements, coupled with recent findings that add scientificlegitimacy to the use of some medicinal herbs, prompts a question about the origins of herbal medicinein animals and ancestral humans. Medicinal herbs are used by animals and humans with the apparent pro-phylactic effects of reducing the likelihood or severity of illness from pathogens or parasites in the future.Medicinal herbs with anti-inflammatory, antimicrobial, immunomodulatory and/or analgesic propertiesare used in a therapeutic way to treat acute infections and inflammatory conditions, particularly in humans,and could have proven lifesaving to individuals living in nature. Was the origin of such types of herbal med-icine the result of animals and humans learning that specific plant parts are effective for preventing or treat-ing certain maladies, or was the origin a result of natural selection for a behavioural predisposition to seekout and use plant parts with particular physical or chemosensory markers of efficacy? Examining the pre-dictions and requirements of both the learned and evolutionary explanations points primarily to an evolu-tionary model for the origin of herbal medicine that was expanded and enhanced by learning and socialtransmission. The evolutionary explanation accounts for the continued use of ineffective, as well as effec-tive, medicinal herbs and the use of medicinal herbs with toxic effects. In animals one can point to originsof the practice of herbal medicine, as well as other behavioural defences against pathogens and parasites, asanalogues of many aspects of modern human medicine and health care.

� 2005 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Although herbal medicinal products represent a fastgrowth area of health-care products for both humansand companion animals (Eisenberg et al. 1998; Bent &Avins 1999), their use in humans appears to predate re-corded history (Tyler 2000). Reviews of the earliest indica-tions of herbal medicine often refer to the grave ofa Neanderthal man, dated 60 000 years ago, in whichwere found pollen and flower fragments of different me-dicinal plants (Solecki 1971). More recently, investigationof the possessions found on the 5300-year-old ‘iceman’discovered in 1991 in the Italian Alps reported pieces ofbirch fungus, presumably used as a laxative and antibiotic(Capasso 1998). Most herbal medicines of current interesthave come from ancient civilizations of Africa, the Asiansubcontinent, and North, Central and South America(Phillipson 2001). Although use of medicinal herbs ap-pears to be much more prevalent among humans than an-imals, understanding the prominence in human use is

Correspondence: B. Hart, University of California, Department of Anat-omy, Physiology, and Cell Biology, School of Veterinary Medicine, OneShields Avenue, Davis, CA 95616, U.S.A. (email: blhart@ucdavis.edu).

970003–3472/05/$30.00/0 � 2005 The Association for the S

inextricably bound to perspectives gleaned from studiesof self-medication in animals and differences and similar-ities between humans and animals in the types of herbalmedicine practised.In this paper I will examine hypotheses to explain the

origins of herbal medicine in light of issues such as thelong delay between ingestion of a herb and the onset ofmedicinal effects, the persistent use of medicinal herbsthat appear to be ineffective or toxic and the placeboeffect that undoubtedly permeates the practice of herbalmedicine as it does conventional medicine. I will explorewhether learning of some type, or natural selection, mostadequately explains the origin and maintenance of thepractice of the many forms of herbal medicine amonganimals and humans.

BACKGROUND

It has been suggested that the practice of herbal medicinecan generally be divided into prophylactic and therapeuticuses (Phillips-Conroy 1986; Lozano 1998; Johns 1999).Given that illnesses vary from nondetectable to severe,the use of medicinal herbs with regard to being

5tudy of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

ANIMAL BEHAVIOUR, 70, 5976

prophylactic or therapeutic lies along a continuum be-tween these two types of uses. Thus, the designation ofa type of herbal medicine as prophylactic or therapeuticmayoccasionally involve a grey area between the two types.I will use the term ‘prophylactic’ to refer to the preventionor reduction of the likelihood of illnesses ormaladies in thefuture in individuals not showing signs of illness and ‘ther-apeutic’ to refer to use by individuals with an evident mal-ady, such as an acute illness or flare-up of an inflammatoryprocess. The prophylactic use of herbs may be ongoing orperiodic. Periodic use would be expected, for example, ifthe risk of illness or disease varies with season (Lozano1998), whereas the therapeutic use would generally beshort term and restricted to the course of the illness.In most instances, the reported use of medicinal herbs

by animals appears to be prophylactic (see Table 1). Theuse of medicinal herbs in traditional human societies, onthe other hand, appears to be primarily for treatment ofactive or acute conditions. At least, this is the sense con-veyed in the literature on herbal medicines in traditionalsocieties (Perry & Metzger 1980; Iwu 1993; Ghazanfar1994; van Wyk et al. 1997; Ross 1999, 2001; Blumenthalet al. 2000; Chevallier 2000; Parrotta 2001; Williamson2003; Khare 2004). A perusal of the indications in tradi-tional societies for 25 medicinal herbs used by humans,for example, reveals a frequent mention of acute infec-tions or inflammatory conditions including abdominalpain, vomiting, gastrointestinal infections, diarrhea, ulcer-ative colitis, gastritis, intestinal worms, liver problems,nausea, sore throat, arthritis, canker sores, toothacheand fever (Chevallier 2000; see Table 2).For therapeutic treatment of a variety of acute infections

and inflammatory conditions in animals and ancienthumans, I propose that the most logical plant parts wouldbe those with constituents that are anti-inflammatory,analgesic, antimicrobial and/or immunomodulatory.These are properties that should be most effective inreducing the severity or disabling effects of a variety ofinfectious or inflammatory conditions.

The Question of Efficacy

Central to understanding the origin of either prophylacticor therapeutic herbal medicine is the necessity for actualefficacyofmedicinalherbs.Although thehundredsofherbalproducts recommended for long and varied lists of maladiesinvite scepticism about efficacy, research over the pastcouple of decades or so, conducted under current scientificstandards, provides evidence of the medicinal efficacy forsome herbal products especially for therapeutic effects.Efficacy is most difficult to demonstrate for prophylactic

use because the behaviour is based on reducing the severityor likelihood of adverse events in the future. Most evidenceof efficacy is circumstantial, involving correlation betweenthe occasions of use of herbs and times of high risk of thedisease under consideration, and laboratory tests of plantparts for potency in controlling causative agents of thedisease under consideration. Table 1, which outlines ani-mal examples of herbal medicine from data-based studies,particularly illustrates prophylactic use. The consumption

of soil, dirt or clay (geophagy), seen in several herbivorousand omnivorous mammals, is a type of self-medication(Knezevich 1998), but is not included in Table 1 becausethis type of self-medication does not involve plant parts.Fur rubbing with millipedes by wedge-capped capuchinmonkeys,Cebus olivaceus (Valderrama et al. 2000) is anothertype of self-medication that does not involve a plant prod-uct and is similarly not included.

Demonstration of efficacy for the treatment of acuteinfections is straightforward because medicinal herbs, orextracts thereof, can be tested on laboratory animals withinduced conditions or on in vitro preparations to docu-ment efficacy. In fact, tests on laboratory animals, and invitro preparations, are an essential part of the develop-ment of modern medicines for federal approval. What islargely missing for full demonstration of efficacy for thetreatment mode are multiple clinical trials with appropri-ate control groups. As described below, Table 2 summa-rizes evidence from laboratory animal and in vitrostudies of the efficacy of medicinal herbs used in the treat-ment of disease conditions where the anti-inflammatory,antimicrobial, immunomodulatory and/or analgesic prop-erties were examined.

Prophylactic Use of Medicinal Herbs

The most substantial body of published research onanimal use of medicinal herbs is on whole-leaf swallowingby chimpanzees, Pan troglodytes. Observations of wildchimpanzees at several study sites reveal a behaviour inwhich the animals periodically swallow whole leaves,which pass through the intestinal tract intact. The behav-iour is most frequently seen during the rainy season whenthe risk of gastrointestinal nematode infection is highest(Wrangham 1995; Huffman et al. 1996). In most instances,the animals performing the behaviour reportedly show noevident signs of acute illness. However, in one study, chim-panzees seen swallowing whole leaves frequently had signsof diarrhea and an increased tendency to rest or sleep(Huffman et al. 1996). Whole leaves were found in faecesalong with expelled intestinal nematodes. It has been sug-gested that parasites are purged by enhanced gastrointesti-nalmotility induced bywhole-leaf swallowing (Huffman&Caton 2001). Although the diarrhea and tendency to restand sleep suggest a therapeutic mode of herbal medicine,the increased frequency of whole-leaf swallowing, duringthe rainy season, suggests a prophylactic mode.

Another documented type of prophylactic use of me-dicinal herbs is seen in nest fumigation by dusky-footedwood rats, Neotoma fuscipes. Wood rats use the same stick-houses over many seasons and even generations, so thereis a risk of build-up of nestborne ectoparasites, especiallyfleas. Wood rats bring into their stickhouses leafy sprigsof California bay, Umbellularia californica, and toyon, Het-eromeles arbutifolia, along with sprigs of a long-recognizedfood staple, live oak, Quercus spp. Bay leaves are found sig-nificantly more often near the sleeping nest than are otherplants. In in vitro experiments, bay leaves reduced survivalof flea larvae to about 25%, compared to 80–90% survivalfor larvae exposed to leaves of oak, toyon or no leaves

REVIEW 977

Table 1. Examples of therapeutic and prophylactic use of medicinal herbs in animals

Animal species Plant species Marker Postulated effect Evidence of effect References

Bitter pith chewingChimpanzees,Pan troglodytes

Vernonia sp. Bitter taste Treat illness (therapeutic) Correlation withillness

Huffman & Seifu 1989

Antimicrobialextracts

Huffman et al. 1993

Whole-leaf swallowingChimpanzees Aspilia sp. Rough surface Expulsion of tapeworms

(prophylactic/therapeutic)Correlation with risk Wrangham 1995

Chimpanzees Rubia sp. Bristly surface Expulsion of nematodes(prophylactic/therapeutic)

Increased gutmortality

Huffman et al. 1996;Huffman & Caton 2001

Bonobos, Panpaniscus

Manniophyton sp. Expulsion of nematodes(prophylactic/therapeutic)

Correlation with risk Dupain et al. 2002

Nest fumigationStarlings,Sturnus vulgaris

Agrimonia sp.,Daucus sp.

Volatiles Killing nestborne mites,lice (prophylactic)

In vitro tests Clark & Mason 1985

Wood rats,Neotoma fuscipes

Umbellurlaria sp. Volatiles Killing nestborne fleas,(prophylactic)

In vitro tests Hemmes et al. 2002

Fur rubbingCapuchinmonkeys,Cebus capucinus

Unspecified leaves Volatiles Repel ectoparasites; controlbacteria, fungi (prophylactic)

Correlation with risk Baker 1996

White-nosed coatis,Nasua naria

Trattinnickia sp. Volatiles Repelling ectoparasites(propylactic)

Correlation with risk Gompper & Hoylman1993

Consumption of medicinal herbsBaboons,Papio hamadryas

Balanites sp. Control schistosomiasis(prophylactic)

Correlation with risk Phillips-Conroy 1986

(Hemmes et al. 2002). A recent study revealed that bay, aswell as toyon, has flea-repelling properties (A. Alvarado,R. Hemmes & B. L. Hart, unpublished data).Related uses of plants for nest protection have been

studied in European starlings, Sturnus vulgaris, whichweave foliage from herbal plants into the nest matrixwhen eggs are being incubated. In laboratory tests, plantsselected by starlings suppressed the hatching of louse eggsand arrested the development of nestborne mites (Clark &Mason 1985, 1988).Perhaps the most widespread prophylactic use of me-

dicinal herbs in humans is the use of spices in foodpreparation. Evidence for the antimicrobial effects ofspices in reducing the growth of ingested foodbornepathogens and in the preservation of meat, has beenwell documented (Billing & Sherman 1998). A scenariohas been postulated in which ancient humans, living inhot climates, who happened to add spicy plant parts tomeat dishes, suffered less from foodborne illness thanthose who did not and perhaps were able to store foodlonger. The spice-using people were then possibly health-ier and were able to rear more healthy offspring.A review of commonnames of somemedicinal herbs (see

Table 2) below reveals some overlap between plant partsthat are used as spices andmedicinal herbs with antimicro-bial effects. Not surprisingly, traditional herbal gardensmaintained in the Middle Ages, and in modern times, typi-cally include plants that serve as spices andmedicines. Theuse of spices in everyday food preparation could be consid-ered a typeof prophylactic humanherbalmedicine, and theuse of the same plant parts in larger amounts at one timecould be considered a therapeutic use of medicinal herbs.

Therapeutic Use of Medicinal Herbs

In contrast to the widespread therapeutic use of medic-inal herbs in humans, the therapeutic use by animalsappears to be more limited. Perhaps the most convincinganimal example comes from observations on chimpanzeesthat appeared ill. The animals were subsequently observedingesting the pith of young shoots of Vernonia amygdalina;they meticulously removed the outer bark and leaves ofstems to chew and suck upon the extremely bitter pith(Huffman & Seifu 1989; Huffman et al. 1993). Sesquiter-pene lactones, with possible effects on intestinal hel-minths, amoeba and bacterial pathogens, have beenisolated from V. amygdalina (Ohigashi et al. 1991; Jisakaet al. 1992).The lack of comparable observations of self-medication

by ill individuals of other nonhuman species, or even otherchimpanzees, raises the question about possible reasons forthe apparent infrequency with which such self-medicationfor therapeutic purposes occurs in animals in nature. I canthink of three nonmutually exclusive possibilities. (1)There is a low probability that an observer will be presentto observe and record the behaviour of an animal that is illseek out and consume medicinal herbs. (2) Social trans-mission of the behaviour among individuals in a groupmay be less likely in nonverbal animals than in humans(see below). (3) Animalsmay actually become acutely ill lessfrequently than humans, and consequently, only infre-quently use medicinal herbs for therapeutic properties.That nonhuman animals use medicinal herbs less for

therapeutic purposes is suggested by the perspective thatthe evolution of the genus Homo involved a dietary shift to

Study

typez References

IV Haraguchi et al. 1996

LA, IV Bendjeddou et al. 2003LA Matsuda et al. 2003LA Ivanovska & Philipov

1996IV Shamsa et al. 1999LA Safayhi et al. 1991LA Krieglstein et al. 2001LA Olajide et al. 1999IV Akinpelu & Olorunmola

2000LA Olajide et al. 2000IV Talla et al. 2002LA Olajide et al. 2003

ory, LA Sur et al. 2001IV Zvetkova et al. 2001LA Besra et al. 2003LA Ibrahim & Osman 1995IV Khan et al. 2001LA Villasenor et al. 2002IV Somchit et al. 2003LA Claeson et al. 1993IV Hwang et al. 2000LA Rehman et al. 1999LA Mattace Raso et al. 2002LA Fabry et al. 1996IV Fabry et al. 1998IV Freiburghaus et al. 1998LA Olajide & Alada 2001LA Matsuda et al. 1998LA Moon et al. 1999LA Kobayashi 2003LA Utsunomiya et al. 1995LA Utsunomiya et al. 2000LA Lanhers et al. 1992IV Loew et al. 2001IV Jang et al. 2003LA Andersen et al. 2004IV Rehman et al. 1999LA Scazzocchio et al. 2001IV Hwang et al. 2003IV Mahady et al. 2003LA Schempp et al. 1999IV Mattace Raso et al. 2002IV Hubner 2003

AN

IMA

LB

EH

AV

IOU

R,70,

5978

Table 2. Characteristics of 25 medicinal herbs tested in controlled laboratory tests

Scientific name Common name Parts used

Taste in

nature* Documented medicinal effectsy

Alpinia galanga Ginger, siameseginger

Rhizomes, roots,seeds

Spicy Antimicrobial, immunomodulatory

Barberis vulgaris Barberry Root bark, berries Bitter Anti-inflammatory, other(antihistaminic)

Boswellia serrata Frankincense Gum resin, bark Astringent Anti-inflammatory

Bridelia ferruginea Bududi, kisni fruit Stem bark,leaves, fruit

Astringent Anti-inflammatory, antimicrobial,analgesic

Camellia sinensis Tea Roots, leaves,buds

Astringent Anti-inflammatory, immunomodulatother (antidiarrheal)

Cassia alata Candle bush,ringworm bush

Leaves, stem bark,root bark, flowers

NA Anti-inflammatory, antimicrobial,analgesic

Curcuma xanthorrhiza Javanese turmeric Rhizomes Spicy Anti-inflammatory, antimicrobial

Echinacea species(augustifolia, purpura)

Echinacea,coneflower

Leaves, roots Bitter Anti-inflammatory,immunomodulatory

Entada abyssinica Abyssinia entada Roots, leaves,stem bark

NA Anti-inflammatory, antimicrobial

Evodia rutaecarpa Evodia Fruits Bitter Anti-inflammatory, analgesic

Glycyrrhiza glabra Licorice Roots Sweet Antimicrobial, immunomodulatory

Harpagophytumpocumbens

Devil’s claw Roots Bitter Anti-inflammatory, analgesic

Hydrastis canadensis Goldenseal Rhizomes Bitter Antimicrobial, immunomodulatory

Hypericum perforatum St John’s Wort Flowers Bitter Anti-inflammatory, antimicrobial

Nigella sativa Black seed,black cumin

Seeds Spicy Anti-inflammatory, antimicrobial,immunomodulatory, analgesic

LA, IV Haq et al. 1999LA Abdel-Fattah et al. 2000LA Salem & Hossain 2000LA Al-Ghamdi 2001IV Khan et al. 2003IV Lim et al. 2002IV Shin et al. 2002

algesicLA, IV Suresh & Vasudevan

1994LA Ihantola-Vormisto et al.

1997LA Santos et al. 2000LA, IV Kiemer et al. 2003LA Raphael & Kuttan 2003

odulatory, LA Kurokawa et al. 1993LA Das et al. 1999LA Gracious Ross et al. 2001

icrobial LA Fernandez et al. 1996IV Fernandez et al. 1998

icrobial LA Muruganandan et al.2001

IV Shafi et al. 2002icrobial, LA, IV Jain & Kulkarni 1999

IV, LA Williams et al. 1999IV Galelli & Truffa-Bachi

1993LA, IV Riehemann et al. 1999

odulatory IV Zarkovic et al. 2001LA, IV Hajto et al. 2003IV Karagoz et al. 2003

unomodulatory LA Al-Hindawi et al. 1992LA Ziauddin et al. 1996LA, IV Davis & Kuttan 2000

icrobial LA, IV Agarwal et al. 2001IV Thomson et al. 2002LA Penna et al. 2003

s on herbal medicines. In a few instances references to the taste

where anti-inflammatory, antimicrobial, immunomodulatory oration on medicinal effects are listed under references.

REVIEW

979

Panax ginseng Ginseng Roots Sweet Antimicrobial,immunomodulatory

Phyllanthus sp.(amarus, emblica)

Phyllanthus,shatter stone

Leaves, roots Bitter Anti-inflammatory,immunomodulatory, an

Punica granatum Pomegranate Fruit rind, seeds,root bark

Astringent Antimicrobial, immunomother (antidiarrheal)

Scrophularia frutescens Figwort Leaves, stems Bitter Anti-inflammatory, antim

Syzygium cumini Jambal Stem bark, leaves Astringent Anti-inflammatory, antim

Tanacetum parthenium Feverfew Leaves, seeds,flowers

Bitter Anti-inflammatory, antimanalgesic

Urtica dioica Stinging nettle Leaves, rhizomes Astringent Anti-inflammatory,immunomodulatory

Viscum album European mistletoe Leaves, stems NA Antimicrobial, immunom

Withania somniferum Winter cherry,Ashwagandha

Roots, leaves Bitter Anti-inflammatory, imm

Zingiber officinale Ginger Rhizomes Pungent Anti-inflammatory, antim

*Taste in nature of the unprocessed plant part used was obtained from the references in the last column or one or more bookwere not available (NA).yEffects were reported in peer-reviewed, international journals focusing on the medicinal herb in question. In some instancesanalgesic effects were documented, other effects, if documented in references, were also mentioned. The sources of inform

zStudy types refer to analyses in laboratory animals (LA) or in vitro tests (IV).

ANIMAL BEHAVIOUR, 70, 5980

increasing amounts of animal meat and fat (reviewed byJohns 1999; Finch & Stanford 2004). This dietary shift,corresponding to the evolution of a large brain (Kaplan &Robson 2002), had the potential to result in a number ofhealth-eroding effects, including an increase in free radicalsfrom fat metabolism with a simultaneous reduction in in-take of free-radical-scavenging antioxidants in natural veg-etation (Johns 1990, 1999). The increased likelihood ofacute infections and inflammatory conditions in early hu-mans could have set the stage for the natural selection ofthe use of medicinal herbs high in antimicrobial, immuno-modulatory and anti-inflammatory components.

Medicinal Herbs that are Anti-inflammatory,Antimicrobial, Immunomodulatoryand/or Analgesic

It is reasonable to assume that a major emphasis ofherbal medicine use in ancestral humans was on treat-ment of ailments such as inflammatory conditions oracute infections that would have been threatening to anindividual’s immediate survival or welfare. The mostuseful herbs would have been those whose unprocessedparts would have anti-inflammatory, analgesic, immuno-modulatory and/or antimicrobial effects.Table 2 lists 25 medicinal herbs, each of which was the

focus of at least two data-based, laboratory studies con-ducted since 1990 that provided evidence of efficacyfrom anti-inflammatory, analgesic, antimicrobial and/orimmunomodulatory properties when the herbs were con-sumed. Plants with antimicrobial and immunomodulatoryeffects might expedite recovery from acute illness causedby pathogens, and plants with anti-inflammatory and an-algesic effects might alleviate the disabling aspects of in-flammation in one or more organ systems, allowing theindividual to return to normal behaviour, including careof dependent young. The studies considered as providingevidence were experiments using laboratory rodents or invitro analyses.Medicinal herbs considered as candidates for inclusion

in Table 2 were derived from literature searches using ‘me-dicinal plants’ as a common term and searching undereach of the following as a second term: (1) anti-inflamma-tory, (2) analgesic, (3) immunomodulatory, and (4) anti-microbial. I next conducted a literature search on thosemedicinal plants that met the subject criteria, using onlypapers published in peer-reviewed, mainstream interna-tional biomedical journals, including the four peer-re-viewed journals devoted to medicinal herbs (Journal ofEthnopharmacology, Phytomedicine Research, Planta Medica,Fitoterapia). For each plant, I determined whether at leasttwo scientific, data-based, controlled experimental stud-ies, with statistically significant results, had been pub-lished in or after 1990 addressing one or more of thetypes of effects named above. I also sought informationon the part of the plant used and its taste as found in na-ture. Finally, I consulted five books authored by recog-nized authorities for the plants’ taste in nature and partsused (Ross 1999, 2001; Blumenthal et al. 2000; Chevallier2000; Williamson 2003). Table 2 includes the scientific

and common name of the medicinal plants, part(s) typi-cally used, reported taste of the unprocessed part (if thisinformation was available), type of documented medicinaleffect and references to the studies documenting efficacy.

Table 2 is far from exhaustive with regard to the medic-inal plants and the scientific research papers that couldhave been included. The list of references for each herbwas restricted to no more than five. References to researchreports of other medicinal herbs are available (Ross 1999,2001; Blumenthal et al. 2000; Williamson 2003). I inten-tionally excluded medicinal herbs used for behavioural ef-fects such as alleviation of depression, enhancement ofcognitive function or behavioural arousal. In one in-stance, however, I included a herb known primarily asan antidepressant (St John’s Wort, Hypericum perforatum)because there are reports documenting its anti-inflamma-tory and antimicrobial effects, which could have predatedits use as an antidepressant.

Five of the medicinal herbs featured in Table 2 have beensubjected to systematic reviewsormeta-analysesofmultipleclinical trials on humans using randomized, placebo-con-trolled, double-blind, methodologies that met minimal cri-teria formethodological quality. The effects of interest werenot necessarily the same effects reported in Table 2. Thesemedicinal herbs are Echinacea spp. (echinacea) for preven-tion or treatment of the common cold (Melchart et al.1995), H. perforatum (St John’s Wort) for treatment of milddepression (Linde et al. 1996), Panex ginseng (ginseng) forenhancement of physical and mental performance (Vogleret al. 1999), Tancetum parthenium (feverfew) for preventionof migraine (Ernst & Pittler 2000a) and Zingiber officiniale(ginger) for treatment of nausea and vomiting (Ernst & Pit-tler 2000b). The systematic reviews or meta-analyses re-vealed inconsistent results with regard to efficacy.Typically, some trials reported significant effects and somenonsignificant effects, leading the authors of the reviewsormeta-analyses to conclude that at least someof theherbalpreparations in use are more effective than placebo.

Given the expected variability in potency of the herbalplant products in nature, and variability in clinical con-ditions of patients enrolled in such studies, inconsisten-cies in reports of the efficacy of medicinal herbs might beexpected. That is, even if multiple clinical trials of soundmethodology had been conducted with each of the entriesof Table 2, focusing on the medicinal effects profiled inthe table, the results would probably be similar.

Table 2 does not include any putative medicinal herbsfor which ineffectiveness was documented. Undoubtedlymany putative medicinal herbs are no better than placebo,but no purpose would be served by including such nega-tive findings, even if they were available. I will deal withimplications of the variability in the potency of medicinalplant products, including those that are ineffective ortoxic, under discussion of the implications of the evolu-tionary explanation of the origin of herbal medicine.

Disclaimer

Although the research studies cited in Table 2 provideevidence of efficacy for each of the medicinal plants listed,

REVIEW 981

this is not an endorsement of their use. Some medicinalherbs currently marketed are available in concentratedforms and could be toxic or have adverse interactionswith other medications (Ernst 1998). Even a medicinalherb that is toxic may have been beneficial for ancient hu-mans or may be beneficial for free-living animals con-fronted with an acute illness. Such trade-offs cangenerally be avoided with modern pharmaceuticalpreparations.

ALTERNATIVE HYPOTHESES ON THE ORIGIN

OF HERBAL MEDICINE

In general, the two possibilities for the origins of theprophylactic and the therapeutic types of herbal medicineare learning and natural selection. Both explanationsassume that medicinal herbs are effective in preventingor treating conditions at least some of the time. Thelearning explanation seems to be favoured by mostauthors dealing with the occurrence of herbal medicinein animals (e.g. Sapolsky 1994; Huffman 1997, 2001; Loz-ano 1998). Although not explicitly stated, the impressionconveyed by these authors is that individuals learn tochoose from a large array of plants, those plants or plantparts that will be the most effective for a particular mal-ady. Thus, the learning explanation applied to the pro-phylactic use of herbal substances would specify thatindividuals learn the association between the use of a spe-cific medicinal herb (or group of herbs) and the future pre-vention of pain or discomfort from a particular malady.The learning explanation applied to the therapeutic usewould imply that if the use of a specific medicinal herb(or group of herbs) was followed by alleviation of painand discomfort, the individual would use the same prod-uct when that malady occurred again. The reduction ofpain or discomfort could result from resolution of the ill-ness or from relief from inflammation.The explanation based on natural selection for the

prophylactic use would specify an evolved predispositionfor individuals to seek out and use or consume plantproducts that characterize one or more physical or chemo-sensory markers, which in turn are correlated witheffectiveness in preventing or reducing a particular illnessin the future. As applied to the therapeutic use, thisexplanation would specify an evolved predisposition forsick individuals to seek out and consume plant productswith one or more chemosensory markers, and this wouldlead to an increased likelihood of survival or earlier returnto normal activity. An increase in reproductive fitness isassumed to be associated with the evolved predispositions.The use of plant products for prevention or alleviation

of illness is a logical area in which to expect the behaviourto be transmitted by social means, especially amongfamily or clan members. For social transmission to occur,some individuals must first acquire the behaviour to serveas ‘demonstrators’. Although social transmission of ele-ments of herbal medicine would be important in thedissemination of this behaviour, the behaviour must beanchored to an initial learned or evolved acquisition.Below I contrast different learning models with the

natural selection model to evaluate adequate explanationsof the origin of herbal medicine. After dealing with theseapproaches, I then discuss social transmission.The type of herbal medicine considered here is the use

of raw or nonprocessed plant parts that would beavailable to animals or early humans in the naturalenvironment. A choice between the learning and evolu-tionary explanations stems from the different predictionsand/or requirements of each. For the sake of discussion, Icontrast the learning and evolutionary explanations asa dichotomy while acknowledging that, if an evolutionaryorigin seems likely, learning undoubtedly interacted withand reinforced the natural selection process. The relativeimportance of natural selection and learning would bereflected in the particular type of condition being affectedby herbal use.

Learning as a Basis for Herbal Medicine

One model of learning for the acquisition of herbalmedicine is a type of operant conditioning acquiredthrough appropriate reinforcement. Some contingency isrequired between the performance of a behaviour, in thiscase seeking out and using a specific plant or plant part,and its reinforcement. For example, native Americans arereported to have used bay leaves to repel mosquitoes (Balls1962). One can imagine that the initial application of bayleaves to the skin was accidental, but the distinctive aromawould have remained on the skin and could have becomeassociated with the absence of mosquitoes. As another ex-ample, many plant products have reinforcing excitatory,calming or hallucinogenic effects that occur soon after in-gestion and their use could be explained by learning.For a behaviour such as seeking out and using a plant

part for medicinal effects to be learned using the conven-tional operant paradigm, reinforcement must follow theperformance of the behaviour within a fairly short time;this is usually expressed in seconds or minutes rather thanhours, days or weeks (Schwartz & Robbins 1995). Fewlearned operants occur with one trial, so another generalrequirement of operant conditioning is multiple sessionsof reinforced responses. Reinforcement during these mul-tiple trials should also be more continuous than intermit-tent; once learned, the behaviour can be maintained byintermittent reinforcement.Application of the operant learning model to the use of

herbs for the prevention or treatment of illness revealsseveral problems. One is the delay between performanceof the behaviour and reinforcement. For prophylactic use,the delay could be weeks or months. For therapeutic use,acute conditions generally take days to noticeably im-prove, even with modern drugs. Innumerable behaviouralresponses would occur between use of a herbal productand its reinforcement, from the prevention or reduction ofpain or discomfort, days or weeks later.The occurrence of continuous reinforcement, which is

required for efficient acquisition of learned behaviour,presents a problem with variability in the active ingre-dients, and hence their effectiveness on the conditionbeing prevented or treated. In fact, variability in active

ANIMAL BEHAVIOUR, 70, 5982

ingredients is one of the primary criticisms levelledagainst medicinal herbs (Ernst 1998). Various medicalconditions would also be expected to respond differentlyto the same medicinal herbs, lending additional inconsis-tency to the reinforcement effects. Thus, the reinforce-ment following the initial use of a plant part is likely tobe intermittent rather than continuous and not conduciveto learning. Finally, the necessity of multiple trials pointsto a difficulty in the therapeutic use for acute illnesses.Even if a herbal substance had reliable reinforcing proper-ties, the infrequency of the illness would provide few op-portunities for individuals to repeatedly experience thereinforcing effects of a particular medicinal herb.One possible model with regard to the operant learning

paradigm derives from research into mechanisms bywhich animals with a deficiency in a nutrient acquirea specific appetite for substances containing that nutrient.A number of specific appetites are best explained on thebasis of postingestional reinforcing effects (Rogers &Harper 1970; Zahorik 1977; Mori et al. 1991; Markisonet al. 1999). Representative of these studies is one onrats made deficient in two essential amino acids (Markisonet al. 1999). Subjects showed no immediate tendency toconsume these amino acids in a liquid, but over a periodof 23 h they did gradually increase their intake of theseamino acids, presumably as a result of the postingestionalreinforcing effects. Reinforcement seemed to occur within1–4 h and animals were reinforced continuously forchoosing the correct amino acid in multiple trials. Appli-cation of this model, with a much shorter latency to alle-viation of visceral discomfort than in the treatment ofillness and in the many trials with continuous reinforce-ment, does not logically apply to the acquisition of herbalmedicine.The possibility of a type of specialized learning in-

volving a biological predisposition should be mentioned.The paradigm of conditioned food aversions, in whicha learned aversion occurs with only one experience withan ingested toxin that causes gastrointestinal illness hourslater (Gustavson 1977), may suggest a sort of reverse para-digm of one-trial learning with an ingested medicinal herbthat results in alleviation of illness or discomfort days later.Aside from the convincing argument that learned foodaversions do not seem to greatly influence food choiceof animals in nature (Zahorik & Houpt 1981), herbal med-icine differs in essential ways from conditioned food aver-sions. Food aversions involve potential dietary items thatcause an onset of illness within a day or so. Medicinalherbs are generally unpalatable and so they are not poten-tial dietary prospects, and they may or may not lead togradual alleviation of illness over several days. At present,no type of learning involving biological predispositionsappears to account for the origin of most types of herbalmedicine.

Natural Selection as a Basis for HerbalMedicine

No learning paradigm seems to explain the use of herbalmedicines for the prevention or treatment of infections

and organ system dysfunction, but this use can beexplained by natural selection. The evolutionary explana-tion suggests that the initial behavioural predisposition toconsume or use a herbal product was primarily an un-learned response, selected because it enhanced survivaland/or reproductive success by reducing the likelihood orseverity of an illness or inflammatory process.

With regard to the prophylactic use of plant materials,the evolutionary model implies that individuals that usedherbs that prevented illness when they were at risk wereless likely to experience loss of fitness than nonusers. Forexample, wood rats that use larvacidal bay leaves in theirstickhouses (Hemmes et al. 2002) when they are at riskshould leave more healthy offspring than those notengaging in the behaviour.

A useful model regarding the treatment of acute illnessconcerns the one specific appetite for a micronutrient thatdoes not depend on postingestional learning. The specificappetite for sodium is immediate in deficient animals,requiring no experience with the altered state of deficien-cy, and is considered innate (Nachman 1962; Handal1965). Sodium deficiency is fairly common in natureand sodium-deficient animals may be thought of as ill.They will seek out and immediately ingest sodium-con-taining substances with no experience with the deficiency.The behaviour appears to be solely taste-guided, in that itoccurs even under experimental tests that eliminate theinfluence of postingestive reinforcement (Markison et al.1995). The sodium appetite model provides an analoguefor the seeking and consuming of medicinal herbs by indi-viduals with an altered physiological state caused by dis-ease or organ system dysfunction.

If an individual suffering from an inflammatory processor a pathogen-induced illness seeks out and consumesa plant part, the evolutionary explanation implies that theherb has antimicrobial, anti-inflammatory, immunomod-ulatory and/or analgesic effects, and that the individualconsuming such plants does not die or recovers morequickly than do similarly sick individuals without thispredisposition. If this predisposition has a heritable basis,then the selected behavioural predisposition should ex-pand in the population.

Plant Physical or Chemosensory Markers

In addition to the requirement that putative medicinalherbs actually be effective against various ailments andenhance fitness, a requirement for the evolutionaryexplanation for their use is that the herbal product hasa property that serves as a marker of some probability ofefficacy. Such a marker would be analogous to the saltytaste ‘marker’ of sodium-containing substances in thesodium appetite model. In most instances of prophylacticuse of medicinal herbs, such markers would have to bespecific to the syndrome being prevented. Thus, a roughsurface may be a marker for leaves to be swallowed whole(Huffman et al. 1996) and a type of volatile may be amarkerfor plants used for nest fumigation (Hemmes et al.2002).

REVIEW 983

Many active ingredients of medicinal herbs are second-ary plant compounds that serve as toxins for bacterialpathogens, parasites or insects that invade plants (Free-land & Janzen 1974; Swain 1977; Deans & Ritchie 1987;Knobloch et al. 1989; Langenheim 1994). The secondarycompounds, which are often toxic to mammalian species,generally have a repugnant, astringent or bitter taste,which may be considered a marker of toxicity (Garcia &Hankins 1975). Mammals in general dislike or reject bittersubstances (Mattes 1985; Rouseff 1990; Glendinning1994), and one would not expect plant parts to be foodstaples if they were strongly bitter or otherwise objection-able-tasting, with high concentrations of secondarycompounds.A bitter, astringent or repugnant taste, signalling un-

palatability of the plant part, is a logical marker ofmedicinal efficacy. Of the 25 medicinal herbs featured inTable 2, I found information for 22 of them about the tasteas they grow in nature, and a bitter, or astringent taste wasmentioned for 16 of these (Table 3). Typical of what onemight expect in traditional herbal medicine, interviewswith traditional healers in a Mixe Indian community re-vealed that bitter and astringent tastes were profiled in se-lecting plants for medicinal purposes (Heinrich et al.1992). Bitter compounds have been used since antiquityto treat illness, and even today are associated with medi-cines and pharmaceutical efficacy (Brieskorn 1990). Eventhe phrase, ‘a bitter pill’, conveys the notion that medi-cines are bitter.Consistent with the evolutionary explanation, I suggest

that bitter or astringent plant parts were the focus ofnatural selection for medicinal herbs used for therapeuticpurposes. The use of sweet tasting plant parts withmedicinal effects (e.g. licorice, ginseng) may have comeinto use later as aspects of herbal medicine came under thecontrol of learning and social transmission.There are notable exceptions to the universal rejection

of bitter tasting substances. The sampling of bitter sub-stances with potentially medicinally active substances hasbeen noted repeatedly in mice (Glendinning 1994; Vitaz-kova et al. 2001) and has been reported in other mammals(Freeland & Janzen 1974). Modern humans are commonlyattracted to limited consumption of foods with a bittertaste, including quinine water, citrus fruits, coffee, teaand cruciferous vegetables (Johns 1990; Rouseff 1990), al-though the bitter ingredients are usually present in smallamounts. These observations suggest that early humansand animals in nature had a tendency to sample plantparts in their home range and knew what plant partswere bitter, astringent or repugnant. While such behav-iour is useful in avoiding toxic food staples, informationabout bitter or astringent plant parts would also be avail-able to animals and people seeking bitter or astringentplant parts when ill.For an individual sick with an infectious disease, the

attraction to medicinal plant products brings up thepossibility that the illness itself results in a physiologicalattenuation of the unpalatability of bitter-tasting plantparts. That is, plant parts that would normally be rejectedmay be less unattractive to a sick individual. A precedentfor the physiological attenuation of a threshold for bitter

or pungent substances lies in the explanation of thelowered threshold for rejection of bitter substances bywomen in the first trimester of pregnancy. Profet (1988,1992) argued that this reduced acceptance of bitter foodsoccurs in women when the developing fetus is most sus-ceptible to the toxic ingredients of foods with bitter tastes,such as coffee and garlic. An illness-related, increased pref-erence for bitter herbs, would be the reverse phenomenon.Limited observations offer some evidence for increased

acceptability or attraction to bitter substances in sickindividuals. In her early studies, Goodall attempted tohelp sick chimpanzees at Gombe by offering bitter anti-biotics in bananas; she reported that the sick chimpanzeesreadily consumed the treated bitter-tasting bananas, buthealthy chimps avoided them and waited for her to putout unadulterated bananas (J. Goodall, personal commu-nication, cited by Koshimizu et al. 1994). This anecdote isconsistent with the common belief that ill humans are tol-erant of bitter medicine, but this tolerance is not seen inhealthy people or as sick individuals recover (Koshimizuet al. 1994).

Internal Stimuli Evoking Use of MedicinalHerbs by Sick Individuals

A requirement for the evolutionary explanation forusing herbal medicine to treat illnesses is the existenceof one or more physiological stimuli associated with the

Table 3. Summary of medicinal and taste characteristics of 25 me-dicinal herbs

Characteristic Number of herbs (%)

Medicinal effectsAnti-inflammatory* 19 (76%)Antimicrobialy 14 (56%)Immunomodulatoryz 11 (44%)Analgesicx 7 (28%)

Multiple medicinal effectsTwo or more documented effects 24 (96%)Anti-inflammatory and antimicrobial 10 (40%)Anti-inflammatory andimmunomodulatory

6 (24%)

Anti-inflammatory and analgesic 7 (28%)Antimicrobial and immunomodulatory 7 (28%)

Taste characteristics**Bitter 10/22 (45%)Astringent 6/22 (27%)Bitter or astringent 16/22 (73%)Spicy or pungent 4/22 (18%)Sweet 2/22 (9%)

*Anti-inflammatory effects through one or more recognizedpathways.yIncludes effects against pathogenic viruses, bacteria, fungi and pro-tozoan parasites.zBoost humoral or tissue immunity through one or more recognizedpathways.xEffects may stem from reduction of inflammation or recognizedpathway aside from inflammation. All analgesic herbs also haveanti-inflammatory effects.**Taste of plant part used as found in nature was available for only 22

of the medicinal herbs.

ANIMAL BEHAVIOUR, 70, 5984

illness that would provoke a predisposition to seek outand consume an appropriate herbal product. For inflam-matory conditions, the onset or exacerbation of pain ordiscomfort would be the stimulus. For individuals with aninfectious bacterial or viral illness, the physiologicalstimuli are likely to be not only pain or discomfort, butalso nausea, depression and fever, which are produced bythe endogenous pyrogens associated with the onset ofillness. The behavioural signs, currently referred to assickness behaviour, are relatively generic and occur re-gardless of the type of illness (Hart 1988).

Social Transmission

Although I have argued that most uses of herbalmedicines, whether for treatment or prevention of illness,reflected an evolved predisposition, social transmission ofthe behaviour would increase the efficiency with whichappropriate plant parts would be located or used withina group (Huffman & Hirata 2003, 2004). The best modelfor such social transmission of herbal medicine is the facil-itation of acceptance of novel food items by animals whenthey observe another animal (the demonstrator) consum-ing the food item (Galef 1996, 2002). An analogous exam-ple would be social transmission of the consumption ofherbal products for prophylactic purposes, where theproducts are consumed on a regular basis by healthyanimals.The transmission of herbal medicine for therapeutic

purposes from individuals who have acquired the behav-iour in the face of illness, to other group members who aresick, would be expected in humans through verbal andnonverbal communication. In light of recent researchrevealing similar brain activation (anterior insula andanterior cingular cortex) in people who observe otherssuffering from painful stimuli (Carr et al. 2003; Singeret al. 2004), one can envision a mentor ‘feeling another’spain’ and pointing to a bitter-tasting plant part that thesuffering individual should consume. For social transmis-sion to occur involving the therapeutic use in animals,imagine two animals that are sick at the same time, wherethe demonstrator, who had already acquired the behav-iour, consumes small amounts of otherwise unpalatableplant parts in the presence of the similarly ill observer.This type of social transmission, which requires that thedemonstrator be sick at the same time as the observer,would be unlikely except in epidemic-like illnesses.

IMPLICATIONS OF THE EVOLUTIONARY

EXPLANATION

The hypothesis that herbal medicine arose throughnatural selection raises a number of issues that meritfurther discussion.

So Many Medicinal Herbs, So Many Maladies

A dilemma in understanding the origin of the thera-peutic use of medicinal herbs is that it applies to the use of

herbal products for a wide array of diseases, each withdifferent etiologies, organ system involvements, timecourses and response characteristics. There are hundredsof herbal products, and each may be recommended fora list of maladies. Typical of such lists are the conditionsfor which the medicinal herb barberry, Berberis vulgaris, isindicated: amoebic dysentery, cholera, gastrointestinal in-fections, hepatitis, eczema, psoriasis, limited bile flow andgall bladder pains (Chevallier 2000, page 177). Based onthe specialized uses expected from modern syntheticdrugs, such a list evokes scepticism about efficacy of anytype. The medicinal herbs to which sick animals or hu-mans may be attracted also undoubtedly differ in the de-gree to which they contain a therapeutic agentappropriate to the condition of the individual consumingthe herb.

Within the evolutionary perspective, then, what aresome responses to this dilemma? Of the sample of 25medicinal herbs in Table 2, 76% (19) have anti-inflamma-tory, 56% (14) antimicrobial, 44% (11) immunomodulatoryand 28% (7) analgesic effects, with 96% (24) having morethan one of these therapeutic effects (Table 3). Thus, as aninitial response to this dilemma, a medicinal herb is likelyto contain antimicrobial and/or immunomodulatoryagents as well as anti-inflammatory ones. The broad spec-trum of medicinally effective agents in a single herb wouldmake the herb useful for a variety of maladies. Second, an-imals and ancestral humans may have sought out morethan one bitter or astringent plant part. Third, althougha medicinal ingredient may not be an ideal match for a dis-ease syndrome, one or more constituents might providesome benefit. For example, one would not ordinarily treatan upper respiratory viral disease with an antibiotic, but innature a herbal antibiotic could reduce secondary bacterialcomplications. An anti-inflammatory agent may allow anindividual with a painful condition brought about bya bacterial pathogen to go about providing care of depen-dent offspring sooner, even though an antimicrobialagent is medically indicated.

Ineffective and Toxic Medicinal Herbs

The evolutionary explanation must account for notonly the vast array of herbal plants and variety of illnesses,but also the use of plants that share the chemosensorymarkers of medicinally effective herbs but that either haveno medicinal effects or may be toxic. These criticisms arecommonly levelled against putative medicinal herbs(Ernst 1998). At the outset, one would expect the practiceof herbal medicine to include plants having a level of effi-cacy distributed along a continuum ranging from effectiveto ineffective. Medicinal herbs, even with a fraction of thepotency or safety of modern drugs, could be the basis forthe selection of their use as long as some benefit in fitnessaccrued to the user.

There are two aspects to the consideration of ineffectivemedicinal herbs. One involves plants that are not effectivefor some disease syndromes but are effective for othersyndromes. Thus, a herb may appear to be worthless iftested for antibacterial effects but may alleviate a painful

REVIEW 985

flare-up in an arthritic knee joint. Unless the herb is testedfor several types of effects, its value may remain unknown.The other aspect involves plants that have no medicinalvalue whatsoever. Both aspects are addressed in the sameway. As with other behavioural traits related to fitness,a behaviour need only have an occasional effect on fitnessto be maintained by natural selection. This predictionshould be especially true of behaviours that influencesurvival of the individual in question or welfare ofoffspring. The continued use of some ineffective herbsthat are indistinguishable from effective herbs would bepredicted by the evolutionary explanation.Another prediction from the evolutionary explanation

is that herbs that are medicinally effective, but toxic toone or more organ systems, may be retained in the herbalmedicine repertoire. Although the intention is to avoidsuch side effects with modern medicines, the benefitscould outweigh the costs of some loss of organ systemtissue for animals and humans living in nature, and ata life-or-death juncture, or if the care of dependent youngis threatened. This is the commonly accepted paradigmfor the evolutionary persistence of the adaptive value ofthe microbe-suppressing fever response of sick animalswhen febrile temperatures reach tissue-damaging levels(Ewald 1980; Hart 1988).

Advent of the Placebo Effect

Human religious practices that use putative medicinalherbs are rife with verbally communicated expectations ofrecovery or improvement. This expectation, and the sub-sequent influence on recovery or improvement, is knownas the placebo effect (Shapiro & Shapiro 1997). The place-bo effect would, of course, apply to herbal products thatare both medicinally effective and ineffective. Clearlythe placebo effect is enhanced when a patient is told bya medical authority to expect to improve, regardless ofwhether the authority is a modern physician or a tribalhealer. The fact that a proportion of patients improve byvirtue of the placebo effect would help to maintain theuse of an ineffective herbal product. The placebo effect ap-pears to be a function of human cultural and linguisticproperties and not generally available to nonverbalanimals.

CONCLUSIONS: ANIMAL ANALOGUES

OF MEDICINE

I have argued that the origin of herbal medicine inanimals and ancestral humans was largely a reflection ofnatural selection stemming from fitness benefits to indi-viduals that engaged in this behaviour. The cornerstone ofthis explanation, as applied to therapeutic use, is thatindividuals suffering from acute illness or inflammatoryconditions are drawn to bitter or astringent plant partsthat are likely to have anti-inflammatory, antimicrobial,immunomodulatory and/or analgesic effects that may beeffective in a nonspecific manner. This perspective pro-vides an explanation of the wide array of putativemedicinal herbs that are suggested for numerous and

varying maladies. The evolutionary perspective explainswhy ineffective or toxic plant parts may be maintained inthe repertoire of putative medicinal herbs. The evolution-ary perspective also provides an explanation for fitnessbenefits that may be very delayed and indefinite, a per-spective relevant to both the prophylactic and therapeutictypes of herbal medicine.Although the analogues of human herbal medicine (and

subsequently pharmaceuticals) arguably occur in non-human animals, the field of human medicine encom-passes more than just using medicinal substances toprevent or facilitate recovery from disease. We recognizeas essential aspects of human medicine the value ofnursing and caring for sick group members, immunizingyoung and vulnerable group members against agents ofinfectious disease, and the removal or isolation (quaran-tine) of sick individuals that place other group members atrisk. In a previous review, I identified several behaviouralstrategies that are analogues of these essential aspects ofhumanmedicine that nonhuman animals use to deal withpathogens and parasites (Hart 1990). As with my argu-ment that learning is an unlikely explanation for most as-pects of the acquisition of the practice of herbal medicine,learning is also an unlikely explanation of these otherstrategies of disease control, which may be viewed as pil-lars of modern medicine with analogues in animal behav-iour. Correspondingly, it is unlikely that ancient humanslearned about aspects of medicine from nonhuman ani-mals, but rather that the same natural selective forces in-volved in combating pathogens and parasites led tosimilar behaviour defence strategies in both nonhumananimals and ancient humans.

Acknowledgments

Research on wood rats, which provoked my thinkingabout some of the concepts in this review, was supportedby grant IBN-96-17407 from the National Science Foun-dation. The author thanks colleagues Lynette Hart, DickCoss, Dorothy Geitzen, Mike Mooring and the late DaleLott for valuable input and the constructive criticisms offour anonymous referees.

References

Abdel-Fattah, A. M., Matsumoto, K. & Watanabe, H. 2000. Anti-

nociceptive effects of Nigella sativa oil and its major component,

thymoquinone, in mice. European Journal of Pharmacology, 400,89–97.

Agarwal, M., Walia, S., Dhingra, S. & Khambay, B. P. S. 2001. In-sect growth inhibition, antifeedant and antifungal activity of com-

pounds isolated/derived from Zingiber officinale Roscoe (ginger)

rhizomes. Pest Management Science, 57, 289–300.

Akinpelu, D. A. & Olorunmola, F. O. 2000. Antimicrobial activity of

Bridelia ferruginea fruit. Fitoterapia, 71, 75–76.

Al-Ghamdi, M. S. 2001. The anti-inflammatory, analgesic and anti-

pyretic activity of Nigella sativa. Journal of Ethnopharmacology, 76,

45–48.

Al-Hindawi, M., Al-Khafaji, S. H. & Abdul-Nabi, M. H. 1992. Anti-

granuloma activity of Iraqi Withania somnifera. Journal of Ethno-pharmacology, 37, 113–116.

ANIMAL BEHAVIOUR, 70, 5986

Andersen, M. L., Santos, E. H. R., Seabra, M. L. V., daSilva,A. A. B. & Tufik, S. 2004. Evaluation of acute and chronic

treatments with Harpagophytum procumbens on Freund’s adju-vant-induced arthritis in rats. Journal of Ethnopharmacology, 91,

325–330.

Baker, M. 1996. Fur rubbing: use of medicinal plants by capuchin

monkeys (Cebus capucinus). American Journal of Primatology, 38,

263–270.

Balls, E. K. 1962. Early Uses of California Plants. Berkeley: University

of California Press.

Bendjeddou, D., Lalaoui, K. & Satta, D. 2003. Immunostimulating

activity of the hot water-soluble polysaccharide extracts of Anacy-

clus pyrethrum, Alpinia galanga, and Citrullus colocynthis. Journal ofEthnopharmacology, 88, 155–160.

Bent, S. & Avins, A. L. 1999. An herb for every illness? American Jour-nal of Medicine, 106, 259–260.

Besra, S. E., Gomes, A., Ganguly, D. K. & Vedasiromoni, J. R.2003. Antidiarrhoeal activity of hot water extract of black tea

(Camellia sinensis). Phytotherapy Research, 17, 380–384.

Billing, J. & Sherman, P. W. 1998. Antimicrobial functions of spices:

why some like it hot. Quarterly Review of Biology, 73, 4–38.

Blumenthal, M., Brinckman, J., Goldberg, A. (Eds) 2000. Herbal

Medicine. Expanded Commission E Monographs. Austin, Texas:

American Botanical Council.

Brieskorn, C. H. 1990. Physiological and therapeutical aspects of bit-

ter compounds. In: Bitterness in Foods and Beverages (Ed. by R. L.

Rouseff), pp. 25–33. New York: Elsevier.

Capasso, L. 1998. 5300 years ago the Ice Man used natural laxatives

and antibiotics. Lancet, 352, 1864.

Carr, L., Iacoboni, M., Dubeau, M. C., Mazziotta, J. C. & LuigiLenzi, G. 2003. Neural mechanisms of empathy in humans: a relayfrom neural systems for imitation to limbic areas. Proceedings of the

National Academy of Sciences, U.S.A., 100, 5497–5502.

Chevallier, A. 2000. Encyclopedia of Herbal Medicine. 2nd edn. NewYork: DK.

Claeson, P., Panthong, A., Tuchinda, P., Reutrakul, V., Kanjanop-pothi, D., Taylor, W. C. & Santisuk, T. 1993. Three non-phenolic

diarylheptanoids with anti-inflammatory activity from Curcuma

xanthorrhiza. Planta Medica, 59, 451–452.

Clark, L. &Mason, J. R. 1985. Use of nest material as insecticidal and

anti-pathogenic agents by the European starling. Oecologia, 67,

169–176.

Clark, L. & Mason, J. R. 1988. Effects of biologically active plants

used as nest material and the derived benefit to starling nestlings.Oecologica, 77, 174–180.

Das, A. K., Mandal, S. C., Banerjee, S. K., Sinha, S., Das, J., Saha,B. P. & Pal, M. 1999. Studies on antidiarrhoeal activity of Punica

granatum seed extract in rats. Journal of Ethnopharmacology, 68,

205–208.

Davis, L. & Kuttan, G. 2000. Immunomodulatory activity of Witha-

nia somnifera. Journal of Ethnopharmacology, 71, 193–200.

Deans, S. G. & Ritchie, G. A. 1987. Antibacterial activity of plant

essential oils. International Journal of Food Microbiology, 5, 165–

180.

Dupain, J., Van Elsacker, L., Nell, C., Garcia, P., Ponce, F. & Huff-man, M. A. 2002. New evidence for leaf swallowing and Oesopha-gostomum infection in bonobos (Pan paniscus). International

Journal of Primatology, 23, 1053–1062.

Eisenberg, D. M., Davis, R. B., Ettner, S. L., Appel, S., Wilkey, S.,Van Rompay, M. & Kessler, R. C. 1998. Trends in alternative

medicine use in the United States, 1990–1997: results of a fol-

low-up national survey. Journal of the American Medical Association,280, 1569–1575.

Ernst, E. 1998. Harmless herbs? A review of the recent literature.American Journal of Medicine, 104, 170–180.

Ernst, E. & Pittler, M. H. 2000a. The efficacy and safety of feverfew

(Tanacetum parthenium L.): an update of a systematic review. Pub-

lic Health Nutrition, 3, 509–514.

Ernst, E. & Pittler, M. H. 2000b. Efficacy of ginger for nausea and

vomiting: a systematic review of randomized clinical trials. BritishJournal of Anaesthesia, 84, 367–371.

Ewald, P. W. 1980. Evolutionary biology and the treatment of signsand symptoms of infectious disease. Journal of Theoretical Biology,

86, 107–176.

Fabry, W., Okemo, P. O. & Ansorg, R. 1996. Fungistatic and fun-

gicidal activity of East African medicinal plants. Mycoses, 39,

67–70.

Fabry, W., Okemo, P. O. & Ansorg, R. 1998. Antibacterial activity

of East African medicinal plants. Journal of Ethnopharmacology,

60, 79–84.

Fernandez, M. A., Garcia, M. D. & Saenz, M. T. 1996. Antibacterial

activity of the phenolic acids fractions of Scrophularia frutescensand Scrophularia sambucifolia. Journal of Ethnopharmacology, 53,

11–14.

Fernandez, M. A., Saenz, M. T. & Garcia, M. D. 1998. Anti-inflam-

matory activity in rats and mice of phenolic acids isolated from

Scrophularia frutescens. Journal of Pharmacy and Pharmacology,

50, 1183–1186.

Finch, C. B. & Stanford, C. B. 2004. Meat-adaptive genes and the

evolution of slower aging in humans. Quarterly Review of Biology,79, 3–50.

Freeland, W. J. & Janzen, D. H. 1974. Strategies in herbivory bymammals: the role of plant secondary compounds. American Nat-

uralist, 108, 889–894.

Freiburghaus, F., Steck, A., Pfander, H. & Brun, R. 1998. Bioassay-

guided isolation of a diastereoisomer of kolavenol from Entada

abyssinica active on Trypanosoma brucei rhodesiense. Journal of Eth-

nopharmacology, 61, 179–183.

Galef, B. G., Jr. 1996. Social enhancement of food preferences in

Norway rats: a brief review. In: Social Learning of Animals: the Rootsof Culture (Ed. by C. M. Heyes & B. G. Galef, Jr), pp. 49–64. New

York: Academic Press.

Galef, B. G., Jr. 2002. Social learning of food preferences in rodents:

rapid appetitive learning. In: Current Protocols in Neuroscience (Ed.

by J. N. Crawley, C. R. Gerfen, M. A. Rogawski, D. R. Sibley, P.

Skolnick & S. Wray), pp. 8.5D1–8.5D8. New York: J. Wiley.

Galelli, A. & Truffa-Bachi, P. 1993. Urtica dioica afflutinin: a superan-

tigenic lectin from stinging nettle rhizome. Journal of Immunology,151, 1821–1831.

Garcia, J. & Hankins, W. G. 1975. The evolution of bitter and theacquisition of toxiphobia. In: Olfaction and Taste F. Proceedings of

the 5th International Symposium in Melbourne, Australia (Ed. by

D. A. Denton & J. P. Coghlan), pp. 39–49. New York: Academic

Press.

Ghazanfar, S. A. 1994. Handbook of Arabian Medicinal Plants. Boca

Raton, Florida: CRC Press.

Glendinning, J. I. 1994. Is the bitter rejection response always adap-

tive? Physiology & Behavior, 56, 1217–1227.

Gompper, M. E. & Hoylman, A. M. 1993. Grooming with Trattin-

nickia resin: possible pharmaceutical use by coatis in Panama. Jour-nal of Tropical Ecology, 9, 533–540.

Gracious Ross, R., Selvasubramanian, S. & Jayasundar, S. 2001.Immunomodulatory activity of Punica granatum in rabbitsda pre-

liminary study. Journal of Ethnopharmacology, 78, 85–87.

Gustavson, C. R. 1977. Comparative and field aspects of learnedfood aversions. In: Learning Mechanisms in Food Selection (Ed. by

L. M. Barker, M. R. Best & M. Domjan), pp. 23–43. Baylor, Texas:

Baylor University Press.

Hajto, T., Berki, R., Boldizsar, F. & Nemeth, P. 2003. Galactoside-

specific plant lectin, Viscum album agglutinin-I induces enhanced

REVIEW 987

proliferation and apoptosis of murine thymocytes in vivo. Immu-

nology Letters, 86, 23–27.

Handal, P. J. 1965. Immediate acceptance of sodium salts by sodi-

um-deficient rats. Psychonomic Science, 3, 315–316.

Haq, A., Lobo, P. I., Al-Tufail, M., Rama, N. R. & Al-Sedairy, S. T.1999. Immunomodulatory effect of Nigella sativa proteins frac-

tionated by ion exchange chromatography. International Journalof Immunopharmacology, 21, 283–295.

Haraguchi, H., Kuwata, Y., Inada, K., Shingu, K., Miyahara, K.,Nagao, M. & Yagi, A. 1996. Antifungal activity from Alpinia gal-

angal. Planta Medica, 62, 308–313.

Hart, B. L. 1988. Biological basis of the behavior of sick animals.

Neuroscience and Biobehavioral Reviews, 12, 123–137.

Hart, B. L. 1990. Behavioral adaptations to pathogens and parasites:

five strategies. Neuroscience and Biobehavioral Reviews, 14, 273–

294.

Heinrich, M., Rimpler, H. & Barrera, N. A. 1992. Indigenous phy-

totherapy of gastrointestinal disorders in lowland Mixe communi-

ty (Oaxaca, Mexico): ethnopharmacologic evaluation. Journal ofEthnopharmacology, 36, 63–80.

Hemmes, R., Alvarado, A. & Hart, B. L. 2002. Use of California bayfoliage by wood rats for possible fumigation of nest-borne ecto-

parasties. Behavioral Ecology, 13, 381–385.

Hubner, A. T. 2003. Treatment with Hypericum perforatum L. does

not trigger decreased resistance in Staphylococcus aureus against

antibiotics and hyperforin. International Journal of Phytotherapy &

Phytopharmacology, 3, 206–210.

Huffman, M. A. 1997. Current evidence for self-medication in pri-

mates: a multidisciplinary perspective. Yearbook of Physical Anthro-pology, 40, 171–200.

Huffman, M. A. 2001. Self-medicative behavior in the African greatapes: an evolutionary perspective into the origins of human tradi-

tional medicine. Bioscience, 51, 651–661.

Huffman, M. A. & Caton, J. M. 2001. Self-induced increase of gutmotility and the control of parasitic infections in wild chimpan-

zees. International Journal of Primatology, 22, 329–346.

Huffman, M. A. & Hirata, S. 2003. Biological and ecological foun-

dations of primate behavioral traditions. In: The Biology of Tradi-

tions (Ed. by D. M. Fragaszy & S. Perry), pp. 267–296.Cambridge: Cambridge University Press.

Huffman, M. A. & Hirata, S. 2004. An experimental study of leaf

swallowing in captive chimpanzees: insights into the origins ofa self-medicative behavior and the role of social learning. Primates,

45, 113–118.

Huffman, M. A. & Seifu, M. 1989. Observations on the illness and

consumption of a possibly medicinal plant Vernonia amygdalina

(Del.), by a wild chimpanzee in the Mahale Mountains NationalPark, Tanzania. Primates, 30, 51–63.

Huffman, M. A., Gotoh, S., Izutsu, D., Koshimizu, K. & Kalunde,M. S. 1993. Further observations on the use of Vernonia amyg-

dalina by a wild chimpanzee, its possible effect on parasite

load, and its phytochemistry. African Study Monographs, 14,

227–240.

Huffman, M. A., Page, J. E., Sukhdeo, M. V. K., Gotoh, S., Ka-lunde, M. S., Chandrasiri, T. & Towers, G. H. N. 1996. Leaf-swal-lowing by chimpanzees: a behavioral adaptation for the control of

strongyle nematode infections. International Journal of Primatology,

17, 475–503.

Hwang, J., Shim, J., Baek, N. & Pyun, Y. 2000. Xanthorrhizol: a po-

tential antibacterial agent from Curcuma xanthorrhiza against

Streptococcus mutans. Planta Medica, 66, 196–197.

Hwang, B. Y., Roberts, S. K., Chadwick, L. R., Wu, C. D. & King-horn, A. D. 2003. Antimicrobial constituents from goldenseal(the rhizomes of Hydrastis canadensis) against selected oral patho-

gens. Planta Medica, 69, 623–627.

Ibrahim, D. & Osman, H. 1995. Antimicrobial activity of Cassia

alata from Malaysia. Journal of Ethnopharmacology, 45, 151–

156.

Ihantola-Vormisto, A., Summanen, J., Kankaanranta, H., Vuorela,H., Asmawi, Z. M. & Moilanen, E. 1997. Anti-inflammatory activ-ity of extracts from leaves of Phyllanthus emblica. Planta Medica,

63, 518–524.

Ivanovska, N. & Philipov, S. 1996. Study on the anti-inflammatory

action of Berberis vulgaris root extract, alkaloid fractions and pure

alkaloids. International Journal of Immunopharmacology, 18, 553–

561.

Iwu, M. M. 1993. Handbook of African Medicinal Plants. Boca Raton,

Florida: CRC Press.

Jain, N. K. & Kulkarni, S. K. 1999. Antinociceptive and anti-inflam-

matory effects of Tanacetum parthenium L. extract in mice andrats. Journal of Ethnopharmacology, 68, 251–259.

Jang, M., Lim, S., Han, S., Park, J., Shin, I., Kim, J., Kim, N., Lee, J.,Kim, K. & Kim, C. 2003. Harpogophytum procumbens suppresses

lipopolysaccharide-stimulated expressions of cyclooxygenase-2

and inducible nitric oxide synthase in fibroblast cell line L929.

Journal of Pharmacological Sciences, 93, 367–371.

Jisaka, M., Ohigashi, H., Takagaki, T., Nozaki, H., Tada, T., Hirota,M., Irie, R., Huffman, M. A., Nishida, T., Kaji, M. & Koshimizu,K. 1992. Bitter steroid glucosides, vernoniosides A1, A2, and A3

and related B1 from a possible medicinal plant Veronia amygda-

lina, used by wild chimpanzees. Tetrahedron, 48, 625–632.

Johns, T. 1990. With Bitter Herbs They Shall Eat It. Tucson: University

of Arizona Press.

Johns, T. 1999. The chemical ecology of human ingestive behaviors.

Annual Review of Anthropology, 28, 27–50.

Kaplan, H. S. & Robson, A. J. 2002. The emergence of humans: the

coevolution of intelligence and longevity with intergenerational

transfers. Proceedings of the National Academy of Sciences, U.S.A.,99, 10221–10226.

Karagoz, A., Onay, E., Arda, N. & Kuru, A. 2003. Antiviral potencyof mistletoe (Viscum album sp. album) extracts against human par-

ainfluenza virus type 2 in vitro cells. Phytotherapy Research, 17,

560–562.

Khan, M. R., Kihara, M. & Omoloso, A. D. 2001. Antimicrobial ac-

tivity of Cassia alata. Fitoterapia, 72, 561–564.

Khan, M. A. U., Ashfaq, M. K., Zuberi, H. S., Mahood, M. S. &Gilani, A. H. 2003. The in vivo antifungal activity of the aqueous

extract from Nigella sativa seeds. Phytotherapy Research, 17,183–186.

Khare, C. P. 2004. Indian Herbal Remedies. Berlin: Springer–Verlag.

Kiemer, A. K., Hartung, T., Huber, C. & Vollmar, A. M. 2003. Phyl-

lanthus amarus has anti-inflammatory potential by inhibition ofiNOS, COX-2, and cytokines via the NF-kB pathway. Journal of

Hepatology, 38, 289–297.

Knezevich, M. 1998. Geography as a therapeutic mediator of endo-

parasitism in a free-ranging group of rhesus macaques (Macaca

mulatta). American Journal of Primatology, 44, 71–82.

Knobloch, K. A., Pauli, A., Iberl, B., Weigand, H. & Weis, N. 1989.

Antibacterial and antifungal properties of essential oil compo-

nents. Journal of Essential Oils Research, 1, 119–128.

Kobayashi, Y. 2003. The nociceptive and anti-nociceptive effects of

evodiamine from fruits of Evodia rutaecarpa in mice. Planta Medica,69, 425–428.

Koshimizu, K., Ohigashi, H. & Huffman, M. A. 1994. Use of Verno-

nia amygdalina by wild chimpanzees: possible roles of its bitter re-lated constituents. Physiology & Behavior, 56, 1209–1216.

Krieglstein, C. F., Anthoni, C., Rijcken, E. J. M., Laukotter, M.,Spiegel, H.-U., Boden, S. E., Schweizer, S., Safayhi, H., Sen-ninger, N. & Schurmann, G. 2001. Acetyl-11-keto-B-boswellic

acid, a constituent of herbal medicine from Boswellia serrata resin,

ANIMAL BEHAVIOUR, 70, 5988

attenuates experimental ileitis. International Journal of Colorectal

Disease, 16, 88–95.

Kurokawa, M., Ochiai, H., Nagasaka, K., Neki, M., Xu, H., Kadota,S., Sutardjo, S., Matsumoto, T., Namba, T. & Shiraki, K. 1993.

Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus, and measles virus in vitro and their therapeutic

efficacies for HSV-1 infection in mice. Antiviral Research, 22,

175–188.

Langenheim, J. H. 1994. Higher plant terpenoids: a phytocentric

overview of their ecological roles. Journal of Chemical Ecology,

20, 1223–1280.

Lanhers, M., Fleurentin, J., Mortier, F., Vinche, A. & Younos, C.1992. Anti-inflammatory and analgesic effects of an aqueous ex-tract of Harpagophytum procumbens. Planta Medica, 58, 117–

123.

Lim, D. S., Bae, K. G., Jung, I. S., Kim, C. H., Yun, Y. S. & Song,J. Y. 2002. Anti-septicaemic effect of polysaccharide from Panax

ginseng by macrophage activation. Journal of Infection, 45, 32–38.

Linde, K., Ramirez, G., Mulrow, C. D., Pauls, A., Weidenhammer,W. & Melchart, D. 1996. St. John’s Wort for depression: an over-

view and meta-analysis of randomised clinical trials. British MedicalJournal, 313, 253–258.

Loew, D., Mollerfeld, J., Schrodter, A., Puttkammer, S. & Kaszkin,M. 2001. Investigations on the pharmacokinetic properties of Har-

pagophytum extracts and their effects on eicosanoid biosynthesis

in vitro and ex vivo. Clinical Pharmacology & Therapeutics, 69,

356–364.

Lozano, G. A. 1998. Parasitic stress and self-medication in wild ani-

mals. Advances in the Study of Behavior, 27, 291–317.

Mahady, G. B., Pendland, S. L., Stoia, A. & Chadwich, L. R. 2003.

In vitro susceptibility of Helicobacter pylori to isoquinoline alkaloidsfrom Sanguinaria canadensis and Hydrastis canadensis. Phytother-

apy Research, 17, 217–221.

Markison, S., St John, S. J. & Spector, A. C. 1995. Glossopharyng-

eal nerve transection does not compromise the specificity of taste-

guided sodium appetite in rats. American Journal of Physiology,

269, R215–R221.

Markison, S., Gietzen, D. W. & Spector, A. C. 1999. Essential ami-

no acid deficiency enhances long-term intake but not short-termlicking of the required nutrient. Journal of Nutrition, 129, 1604–

1612.

Matsuda, H., Yoshikawa, M., Iinuma, M. & Kubo, M. 1998. Anti-

nociceptive and anti-inflammatory activities of limonin isolated

from the fruits of Evodia rutaecarpa var. bodinieri. Planta Medica,

64, 339–342.

Matsuda, H., Pongipiriyadacha, Y., Morikawa, T., Ochi, M. &Yoshikawa, M. 2003. Gastroprotective effects of phenylpropa-noids from the rhizomes of Alpinia galangal in rats: structural

requirements and mode of action. European Journal of

Pharmacology, 471, 59–67.

Mattace Raso, G., Pacilio, M., Di Carlo, G., Espposito, E., Pinto,L. & Rosaria, M. 2002. In-vivo and in-vitro anti-inflammatory

effect of Echinacea purpurea and Hypericum perforatum. Journalof Pharmacy and Pharmacology, 54, 1379–1383.

Mattes, R. D. 1985. Gustation as a determinant of indigestion:methodological issues. American Journal of Clinical Nutrition, 41,

672–683.

Melchart, D., Linde, K., Worku, F., Sarkady, L., Holzmann, M.,Jurcic, K. & Wagner, H. 1995. Results of five randomized studies

on the immunomodulatory activity of preparations of echinacea.

Journal of Alternative and Complementary Medicine, 5, 145–160.

Moon, T. C., Murakami, M., Kudo, I., Son, K. H., Kim, H. P., Kang,S. S. & Chang, H. W. 1999. A new class of COX-2 inhibitor, rutae-carpine from Evodia rutaecarpa. Inflammation Research, 48, 621–

625.

Mori, M., Dawada, T., Ono, T. & Torii, K. 1991. Taste preference

and protein nutrition and L-amino acid homeostasis in male

Sprague–Dawley rats. Physiology & Behavior, 49, 987–995.

Muruganandan, S., Srinivasan, K., Chandra, S., Tandan, J., Lal,J. & Raviprakash, V. 2001. Anti-inflammatory activity of Syzygiumcumini bark. Fitoterapia, 72, 369–375.

Nachman, M. 1962. Taste preferences for sodium salts by adrenal-ectomized rats. Journal of Comparative Physiology and Psychology,

55, 1124–1129.

Ohigashi, H., Jisaka, M., Takagaki, T., Nozaki, H., Tada, T., Huff-man, M. A., Nishida, T., Kaji, M. & Koshimizu, K. 1991. Bitter

principle and a related steroid glucoside from Vernonia amygda-

lina, a possible medicinal plant for wild chimpanzees. Agriculturaland Biological Chemistry, 55, 1201–1203.

Olajide, O. A. & Alada, A. R. A. 2001. Studies on the anti-inflamma-tory properties of Entada abyssinica. Fitoterapia, 72, 492–496.

Olajide, O. A., Makinde, J. M., Okpako, D. T. & Awe, S. O. 1999.Effects of the aqueous extract of Bridelia ferruginea stem bark

on carrageenan-induced oedema and granuloma tissue forma-

tion in rats and mice. Journal of Ethnopharmacology, 66, 113–

117.

Olajide, O. A., Makinde, J. M., Okpako, D. T. & Awe, S. O. 2000.

Studies on the anti-inflammatory and related pharmacologicalproperties of the aqueous extract of Bridelia ferruginea stem bark.

Journal of Ethnopharmacology, 71, 153–160.

Olajide, O. A., Okpako, D. T. & Makinde, J. M. 2003. Anti-inflam-

matory properties of Bridelia ferruginea stem bark inhibition of lipo-

polysaccharide-induced septic shock and vascular permeability.

Journal of Ethnopharmacology, 88, 221–224.

Parrotta, J. A. 2001. Healing Plants of Peninsular India. Oxon: CAB

International.

Penna, S. C., Medeiros, M. V., Aimbire, F. S. C., Faria-Neto,H. C. C. & Sertie, R. A. B. 2003. Anti-inflammatory effect of thehydralcoholic extract of Zingiber officinale rhizomes on rat paw

and skin edema. International Journal of Phytotherapy and Phyto-

pharmacology, 10, 381.

Perry, L. M. & Metzger, J. 1980. Medicinal Plants of East and South-

east Asia: Attributed Properties and Uses. Cambridge, Massachu-

setts: MIT Press.

Phillips-Conroy, J. E. 1986. Baboons, diet and disease: food plant

selection and schistosomiasis. In: Current Perspectives in Primate So-cial Dynamics (Ed. by D. M. Taub & F. A. King), pp. 287–304. New

York: Van Nostrand Rheinhold.

Phillipson, J. D. 2001. Phytochemistry and medicinal plants. Phyto-

chemistry, 56, 237–245.

Profet, M. 1988. The evolution of pregnancy sickness as protection

to the embryo against pleistocene teratogens. Evolutionary Theory,

8, 177–190.

Profet, M. 1992. Pregnancy sickness as adaptations: a deterrent to

maternal ingestion of tertatogens. In: The Adopted Mind (Ed. by

J. H. Barkow, L. Cosmides & J. Toody), pp. 327–365. New York:Oxford University Press.

Raphael, K. R. & Kuttan, R. 2003. Inhibition of experimental gastriclesion and inflammation by Phyllanthus amarus extract. Journal of

Ethnopharmacology, 87, 193–197.

Rehman, J., Dillow, J. M., Carter, S. M., Chou, J., Le, B. & Maisel,A. S. 1999. Increased production of antigen-specific immunoglo-

bulins G and M following in vivo treatment with the medicinal

plants Echinacea angustifolia and Hydrastis canadensis. ImmunologyLetters, 68, 391–395.

Riehemann, K., Behnke, B. & Schulze-Osthoff, K. 1999. Plant ex-tracts from stinging nettle (Urtica dioica), an antirheumatic

remedy, inhibit the proinflammatory transcription factor NF-

kB. Federation of European Biochemical Society Letters, 442,

89–94.

REVIEW 989

Rogers, Q. R. & Harper, A. E. 1970. Selection of a solution contain-

ing histidine by rats fed a histidine-imbalanced diet. Journal of

Comparative Physiology and Psychology, 72, 66–71.

Ross, I. A. 1999. Medicinal Plants of the World: Chemical Constituents,

Traditional and Modern Medicinal Uses. Vol. 1. Totowa, New Jersey:Humana Press.

Ross, I. A. 2001. Medicinal Plants of the World: Chemical Constituents,Traditional and Modern Medicinal Uses. Vol. 2. Totowa, New Jersey:

Humana Press.

Rouseff, R. L. 1990. Bitterness in Foods and Beverages. New York:

Elsevier.

Safayhi, H., Mack, T. & Ammon, H. P. T. 1991. Protection by bos-

wellic acids against galactosamine/endotoxin-induced hepatitis in

mice. Biochemical Pharmacology, 41, 1536–1537.

Salem, M. L. & Hossain, M. S. 2000. Protective effect of black seed

oil from Nigella sativa against murine cytomegalovirus infection.

International Journal of Immunopharmacology, 22, 729–740.

Santos, A. R. S., De Campos, R. O. P., Miguel, O. G., Filho, V. C.,Siani, A. C., Yunes, R. A. & Calixto, J. B. 2000. Antinociceptiveproperties of extracts of new species of plants of the genus Phyllan-

thus (Euphorbiacceae). Journal of Ethnopharmacology, 72, 229–

238.

Sapolsky, R. M. 1994. Fallible instinct: a dose of skepticism about

the medicinal ‘knowledge’ of animals. Sciences, 34, 13–16.

Scazzocchio, F., Cometa, M. F., Tomassini, L. & Palmery, M.2001. Antibacterial activity of Hydrastis canadensis extract and its

major isolated alkaloids. Planta Medica, 67, 561–564.

Schempp, C. M., Pelz, K., Wittmer, A., Schopf, E. & Simon, J. C.1999. Antibacterial activity of hyperforin from St John’s wortagainst multiresistant Staphylococcus aureus and Gram-positive

bacteria. Lancet, 353, 2129.

Schwartz, B. & Robbins, S. J. 1995. Psychology of Learning and Be-

havior. 4th edn. New York: W.W. Norton.

Shafi, P. M., Rosamma, M. K., Jamil, K. & Reddy, P. S. 2002. An-tibacterial activity of Syzygium cumini and Syzygium travancoricum

leaf essential oils. Fitoterapia, 73, 414–416.

Shamsa, F., Ahmadiani, A. & Khosrokhavar, R. 1999. Antihistaminic

and anticholinergic activity of barberry fruit (Berveris vulgaris)

in the guinea-pig ileum. Journal of Ethnopharmacology, 64,161–166.

Shapiro, A. K. & Shapiro, E. 1997. The Powerful Placebo: from An-

cient Priest to Modern Physician. Baltimore, Maryland: Johns Hop-kins University Press.

Shin, J., Song, J., Yun, Y., Yang, H., Rhee, D. & Pyo, S. 2002.Immunostimulating effects of acidic polysaccharides extract of

Panax ginseng on macrophage function. Immunopharmacology

and Immunotoxicology, 24, 469–482.

Singer, T., Seymour, B., O’Doherty, J., Kaube, H., Dolan, R. J. &Frith, C. D. 2004. Empathy for pain involves the affective butnot sensory components of pain. Science, 303, 1157–1162.

Solecki, M. 1971. Shanidar: the First Flower People. New York: Alfred

A. Knopf.

Somchit, M. N., Reezal, I., Elysha Nur, I. & Mutalib, A. R. 2003. In

vitro antimicrobial activity of ethanol and water extracts of Cassiaalata. Journal of Ethnopharmacology, 84, 1–4.

Sur, P., Chaudhuri, T., Vedasiromoni, J. R., Gomes, A. & Ganguly,D. K. 2001. Antiinflammatory and antioxidant property of sapo-

nins of tea [Camellia sinensi (L.) O. Kuntze] root extract. Phytother-

apy Research, 15, 174–176.

Suresh, K. & Vasudevan, D. M. 1994. Augmentation of murine nat-

ural killer cell and antibody dependent cellular cytotoxicity activi-

ties by Phyllanthus emblica, a new immunomodulator. Journal ofEthnopharmacology, 44, 55–60.

Swain, T. 1977. Secondary compounds as protective agents. AnnualReview of Plant Physiology, 28, 479–501.

Talla, E., Djamen, D., Djoulde, D. R., Tatsadjeu, L., Tantoh, D.,Mbafor, J. T. & Fomum, Z. T. 2002. Antimicrobial activity of

Bridelia ferruginea leaves extracts. Fitoterapia, 73, 343–345.

Thomson, M., Al-Qattan, K. K., Al-Sawan, S. M., Alnaqeeb, M. A.,Khan, I. & Ali, M. 2002. The use of ginger (Zingiber officinaleRosc.) as a potential anti-inflammatory and antithrombotic agent.

Prostaglandins, Leukotrienes and Essential Fatty Acids, 67, 475–478.

Tyler, V. E. 2000. Herbal medicine: from the past to the future.

Public Health Nutrition, 3, 447–452.

Utsunomiya, T., Kobayashi, M., Herndon, D. N., Pollard, R. B. &Suzuki, F. 1995. Glycyrrhizin (20b-carboxy-11-oxo-30-norolean-

12-en-3b yl-2-O-b-D-glucopyranouronosyl-a-D-glucopyranosidur-

onic acid) improves the resistance of thermally injured mice toopportunistic infection of herpes simplex virus type 1. Immunology

Letters, 44, 59–66.

Utsunomiya, T., Ito, M., Pollard, R. B. & Suzuki, G. 2000. Glycyr-

rhizin improves the resistance of MAIDS mice to opportunistic

infection of Candida albicans through the modulation of MAIDS-

associated type 2 T cell responses. Clinical Immunology, 95,145–155.

Valderrama, X., Robinson, J. G., Attygalle, A. B. & Eisner, T. 2000.Seasonal anointment with millipedes in wild primate: a chemical

defense against insects. Journal of Chemical Ecology, 26, 2781–

2790.

Villasenor, I. M., Canlas, A. P., Pascua, M. P. I., Sabando, M. N. &Soliven, L. A. P. 2002. Bioactivity studies on Cassia alata Linn. leaf

extracts. Phytotherapy Research, 16, S93–S96.

Vitazkova, S. K., Long, E., Paul, A. & Glendinning, J. I. 2001. Mice

suppress malaria infection by sampling a bitter chemotherapyagent. Animal Behaviour, 61, 887–894.

Vogler, B. K., Pittler, M. H. & Ernst, E. 1999. The efficacy of gin-seng: a systematic review of randomized clinical trials. European

Journal of Clinical Pharmacology, 55, 567–575.

Williams, C. A., Harborne, J. B., Geiger, H., Robin, J. & Hoult, S.1999. The flavonoids of Tanacetum parthenium and T. vulgare

and their anti-inflammatory properties. Phytochemistry, 51, 417–

423.

Williamson, E. M. 2003. Potter’s Herbal Cyclopedia. Essex: C.W.

Daniel.

Wrangham, R. 1995. Relationship of chimpanzee leaf-swallowing to

a tapeworm infection. American Journal of Primatology, 37, 297–303.

van Wyk, B. E., van Oudtshoorn, B. & Gericke, N. 1997. MedicinalPlants of South Africa. Pretoria, South Africa: Briza.

Zahorik, D. M. 1977. Associative and non-associative factors inlearned food preferences. In: Learning Mechanisms in Food Selection

(Ed. by L. M. Barker, M. R. Best & M. Domjan), pp. 181–199. Bay-

lor, Texas: Baylor University Press.

Zahorik, D. M. & Houpt, K. A. 1981. Species differences in feeding

strategies, food hazards, and the ability to learn food aversions. In:

Foraging Behavior (Ed. by A. C. Kamil & T. D. Sargent), pp. 289–310. New York: Garland STPM Press.

Zarkovic, N., Vukovic, T., Loncaric, I., Miletic, M., Zarkovic, K.,Borovic, S., Cipak, A., Sabolovic, S., Konitzer, M. & Mang, S.2001. An overview on anticancer activities of the Viscum album ex-

tract Isorel. Cancer Biotherapy and Radiopharmaceuticals, 16, 55–

62.

Ziauddin, M., Phansalkar, N., Patki, P., Diwanay, S. & Patward-han, B. 1996. Studies on the immunomodulatory effects of Ash-wagandha. Journal of Ethnopharmacology, 50, 69–76.

Zvetkova, E., Wirleitner, B., Tram, N. T., Schennach, H. & Fuchs,D. 2001. Aqueous extracts of Crinum latifolium (L.) and Camellia

sinensis show immunomodulatory properties in human peripheral

blood mononuclear cells. International Immunopharmacology, 1,

2143–2150.