Article in Press

G Model JEP-5123; No. of Pages 16 ARTICLE IN PRESS

Journal of Ethnopharmacology xxx (2008) xxx–xxx

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Journal of Ethnopharmacology

journal homepage: www.elsevier.com/locate/jethpharm

Ethnoveterinary use of southern African plants and scientiﬁc evaluation of their medicinal properties

L.J. McGaw ∗, J.N. Eloff

Phytomedicine Programme, Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa article info abstract

Article history: Aim of the study: Livestock keepers in many developing countries with restricted access to orthodox vet- Received 1 May 2008 erinary healthcare services commonly use traditional remedies to treat their animals when disease is Accepted 12 June 2008 encountered. This review collates the documented use of plants in South Africa for healing various ailments Available online xxx in domestic animals, and records bioactivity testing that has been carried out on these plants. Materials and methods: A literature survey was conducted on the use of plants in South African ethnovet- Keywords: erinary medicine (EVM), as well as on biological activity investigations relating to their ethnoveterinary Ethnoveterinary medicine use where available. Livestock disease South Africa Results: The ethnoveterinary application of plants, and results of screening studies of EVM plant extracts Traditional remedies in various bioassays is presented. For diseases such as coughs, wounds, skin diseases, mild diarrhoea and reproductive disorders, EVM may be a cheap and easily accessible alternative to expensive pharmaceuticals. Studies on biological activity of EVM plants can provide indications of promising leads for extracts that can be developed into standardized medications to be used on a commercial basis. Isolation studies on active plants may yield pure active compounds that could be chemically modiﬁed to optimize medicinal value and reduce possible toxic effects. Conclusion: In South Africa, a large proportion of the population relies on traditional remedies to treat themselves and their animals for common diseases. Only a small percentage of EVM plants have been analysed for biological activity or toxic effects, and hence research in this ﬁeld offers fertile possibilities for future investigation. © 2008 Elsevier Ireland Ltd. All rights reserved.

1. Introduction ery of structurally diverse metabolites with useful pharmacological activities from South African plants. South Africa is home to a rich temperate flora, possessing In South Africa, as in many other developing countries, the rich approximately 24 000 species comprising more than 10% of the cultural diversity is reflected in the use of plants as medicines, and world’s vascular plant flora (Germishuizen and Meyer, 2003). Plants it has been estimated that up to 60% of South Africans consult produce a diverse array of secondary metabolites with many func- traditional healers, usually in addition to making use of ortho- tions, such as defense against herbivores, diseases and parasites dox medical services (Van Wyk et al., 1997). In the case of animal (Cowan, 1999; Pieters and Vlietinck, 2005). These chemicals from diseases, it appears that the owners of the livestock will gener- plants may possess complex chemical structures that are not avail- ally treat their own animals using medicinal plant knowledge that able in synthetic compound libraries. There are estimated to be they themselves possess, rather than consulting traditional healers. 250 000 plant species in the world, and only 5–15% of these species Masika et al. (2000) estimated that 75% of rural livestock owners have been tested for potentially useful biologically active com- in the Eastern Cape (South Africa) use plants or plant-based reme- pounds (Pieters and Vlietinck, 2005). There are exciting possibilities dies to treat animal ailments. Diseases of livestock potentially have for using plants as a source for the discovery of novel lead struc- severe economic impacts in terms of production losses following tures to be used in drug production, and also for the development mortality and morbidity, particularly in the case of cultures where of active plant extracts useful in treating a variety of ailments in animals are equated to wealth. Such diseases also impact on the humans and animals. There is encouraging potential for the discov- health and well-being of companion animals. The search for effective and affordable remedies to combat diseases in animals, as is the case in human medicine, is ongoing.

Abbreviations: EVM, ethnoveterinary medicine. Ethnoveterinary medicine (EVM) comprises a complex system ∗ Corresponding author. Tel.: +27 12 529 8351; fax: +27 12 529 8525. of beliefs, skills, knowledge and practices relating to animal hus- E-mail address: [email protected] (L.J. McGaw). bandry and general animal care (McCorkle, 1986). The practice of

Please cite this article in press as: McGaw, L.J., Eloff, J.N., Ethnoveterinary use of southern African plants and scientiﬁc evaluation of their medicinal properties. J Ethnopharmacol (2008), doi:10.1016/j.jep.2008.06.013 G Model JEP-5123; No. of Pages 16 ARTICLE IN PRESS

2 L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx

EVM includes the use of diagnostic procedures, animal husbandry The treatment of livestock diseases by small-scale farmers in practices, surgical methods and traditional veterinary theory in the Eastern Cape Province of South Africa has been documented addition to the use of ethnoveterinary plants to prevent and con- in several reports (Masika et al., 1997; Masika et al., 2000; Masika trol disease (Schillhorn van Veen, 1996; Van der Merwe et al., 2001). and Afolayan, 2003). Several methods, both qualitative and quan- It is therefore important to keep in mind that lack of activity in a titative, including participatory research methods such as matrix laboratory-based in vitro screening system does not automatically ranking, diagramming and group interviews, were used to obtain correspond to lack of efficacy of a traditional medication. information from local livestock keepers (Masika et al., 2000). This Many aspects of EVM need to be taken into account, for exam- study showed that the use of herbal remedies to treat animal dis- ple methods of preparation and administration of the remedy, eases was widespread amongst small-scale farmers in the Eastern as well as management practices to limit the impact of the dis- Cape, largely because of low cost, convenience and ease of admin- ease. Orthodox treatments are certainly indispensable in cases istration (Masika et al., 2000). As was the case with the study of such as epidemics of contagious diseases, but for common ail- Van der Merwe et al. (2001), Masika et al. (2000) reported that ments, for example mild diarrhoea, skin diseases, intestinal worms there was a possible threat of herbal preparations being toxic. It and wounds, ethnoveterinary medicine may function effectively was recommended that further research is required to optimize (Martin et al., 2001). Shortcomings of ethnomedicine include sea- dosing and concentrations of EVM remedies, as well as identifi- sonal unavailability of plant material, inefficacy or harmfulness of cation of possible side effects and toxicity. According to Van der treatments, as well as lack of dosing certainty and standardization Merwe et al. (2001) it is likely that the small amounts of plant mate- of remedies (Martin et al., 2001). Means of overcoming these dis- rial used in medicines were the reason for the scarcity of reported advantages need to be formulated and should be communicated toxic effects. Other issues raised by Masika et al. (2000) were those to the users of EVM. The benefits of understanding, evaluating and of the urgent need for documentation of rapidly disappearing local ultimately integrating EVM into primary animal healthcare are evi- EVM knowledge, and conservation of medicinal plant resources. dent. Over-exploitation of plants was seen to be a threat to the continued In this paper, the current status of information on ethnoveteri- existence of EVM. nary usage of plants in South Africa, as well as biological activity The treatment of the diseases gallsickness (anaplasmosis) and and toxicity investigations on South African ethnoveterinary plants, redwater (babesiosis) by livestock farmers in the Eastern Cape was will be reviewed. among the subjects of another investigation by Masika et al. (1997). A large majority of farmers interviewed claimed to administer 2. Use of plants for ethnoveterinary purposes in South herbal remedies to treat these tick-borne diseases. Dold and Cocks Africa (2001) interviewed members of 25 households, also in the Eastern Cape Province, to obtain information on the use of 53 plants as vet- Traditional uses of many South African plants have been doc- erinary medicines by stock farmers. Most of the ailments treated umented in several books (Watt and Breyer-Brandwijk, 1962; concerned cattle, and the remainder pertained to goats, sheep and Hutchings et al., 1996; Van Wyk et al., 1997) and journal arti- poultry, with distemper in dogs included as well (Dold and Cocks, cles. However, a complete systematic ethnobotanical recording has 2001). not yet been compiled. There is an urgent need to record indige- Masika and Afolayan (2003) reported that, generally, more than nous knowledge on traditional plant use before it is lost to rapid one plant species is combined for treating livestock in the Eastern urbanization and acculturation, and this includes hitherto relatively Cape, while Van der Merwe et al. (2001) found that most remedies neglected areas such as ethnoveterinary medicine (Van Wyk, 2002). were used in the form of a single plant. The use of single plants as In recent years, South African researchers have ventured into remedies in most cases was confirmed by the findings of Luseba EVM fieldwork investigations with promising results. A Rapid Rural and Van der Merwe (2006). Appraisal (RRA) approach was used by Van der Merwe et al. Luseba and Van der Merwe (2006) made use of RRA methods to (2001) to obtain information on the use of EVM plants in cattle collate indigenous knowledge on animal disease treatment by the by Setswana-speaking people in the North West Province of South Tsonga people of South Africa. These remedies were used because Africa. The RRA data collection approach is an adaptable technique they were thought to be more effective for treating some diseases, aimed at achieving understanding of a rural situation quickly and and also as alternatives to expensive orthodox pharmaceuticals cheaply. In this method, semi-structured interviews are preferred (Luseba and Van der Merwe, 2006). rather than pre-prepared questionnaires, and lines of inquiry are The plants used for EVM purposes in South Africa are listed in adapted to take advantage of new insights as they become apparent Table 1, together with references to the original sources. Plants used (Van der Merwe et al., 2001). for magical purposes, such as for protection against evil, have been Techniques including interviews, observations and guided field excluded. Just over 200 species were found to be used in EVM, with walks were used by Van der Merwe et al. (2001) with people extremely diverse indications being recorded. in the study area involved with livestock production or who had knowledge on EVM. To give some structure to the interviews and information garnered, questions were asked around specific dis- 3. Biological activity investigation of ethnoveterinary ease topics (such as different organ systems), general conditions, plants nutritional conditions, plant poisoning and other forms of poisoning (Van der Merwe et al., 2001). Informants were asked to describe The study of the ethnopharmacological properties of South the symptoms treated as well as the names of the diseases, to African plants in general is a productive research field, and cur- account for the lack of formal veterinary training. Forty-five plant rent endeavours are primarily targeted at validating traditional species from 24 families, used for 29 indications, were recorded plant use, although some attention has been paid to the commer- (Van der Merwe et al., 2001). The most important indications cial potential of plants (Van Wyk, 2002). Relatively little research noted were retained placenta, diarrhoea, gallsickness, fractures, eye has been conducted on the bioactivity of plants used for ethnovet- inflammation, general unwellness, fertility problems, gastrointesti- erinary purposes in particular, and published information on such nal ailments, heartwater, helminthosis, coughing, redwater and bioactivities is summarized in this section, and some notes of the reduction of ticks. plant species tested have been made in Table 1.

L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx 3 McGaw McGaw McGaw McGaw ) ) ) ) ); antibacterial, Luseba et al., 2007 brine shrimp toxicity ( et al., 2007 brine shrimp toxicity ( et al., 2007 brine shrimp toxicity ( et al., 2007 brine shrimp toxicity ( et al., 2007 anti-inflammatory, mutagenic ( ) Watt and ) ) ) ) Watt and Watt and Villegas et al., 1988 Watt and haemolytic saponin ( Breyer-Brandwijk, 1962 Breyer-Brandwijk, 1962 crinidine, dihydrocrinidine and powelline and phenols ( Breyer-Brandwijk, 1962 (antifungal) ( christyoside ( Breyer-Brandwijk, 1962 Root and bark decoctions Roots, bark Antibacterial, anthelmintic, Bark Bark, root bark Volatile oil ( Bulb, root, bulb scales Whole plant infusions Roots Leaf decoction Bark, roots Falcarindiol and sarisan Unspecified Cardiac glycosides stropeside and Bark Antibacterial, anthelmintic, Leaves, roots Aerial partsLeaves, bark Antibacterial, anthelmintic, Antibacterial, anthelmintic, ) Bulb ) Unspecified parts ) Unspecified parts) Alkaloids, organic acid and Unspecified parts Unknown ) Unspecified parts Lycorine, cheryrilline, crinamidine, Dold and ) Dold and Hutchings et Palmer and ) ) Dold and Cocks, Hutchings et al., ) Gerstner, 1938 Gerstner, 1939 Gerstner, 1939 Dold and Cocks, ); Xhosa use roots for Dold and Cocks, 2001 Van der Merwe et al., Van der Merwe et al., Watt and ); redwater, Dold and Cocks, 2001; Van der Merwe et al., Jacot Guillarmod, 1971 )) Masika et al., 2000 ); bark used for retained placenta ) ); abortion ( Gerstner, 1938 Dold and Cocks, 2001 Van der Merwe et al., 2001 ); diarrhoea, redwater, sweating Dold and Cocks, 2001 ) ) ) ) ) ) Cocks, 2001 2001 after an accident, bark given todiarrhoea cows ( for to facilitate healing of broken limbsCocks, ( 2001 al., 1996 sickness ( 2001 gallsickness ( Breyer-Brandwijk, 1962 Zulus use bark for colic, scrofulafor and horses vermifuge ( threadworm in horses ( Used to drench calves suffering fromcondition a referred to as white scours 2001 2001 1996 Given to cattle for snakebite ( cattle, snakebite, anthrax, tapeworm, swollen limbs ( in stock, leaves used to treatand/or endometritis vaginitis in cows, bark decoctiongallsickness for in cattle ( Masika et al., 2000 paralyzed in their hind quarters ( Pitman, 1972 2001 personal communication) (Hook.) Baill. Medicine for cattle ( (Lam.) Codd Heartwater in goats and sheep, redwater in (Wendl.) Eckl. & (Ward & Harv.) (Ker-Gawl.) Herb. Used medicinally for cattle ( Jacq. Healing of broken limbs ( Willd. Diarrhoea in sheep and goats ( (Bernh.) Engl. Heartwater and diarrhoea in cows ( (Thunb.) Aellen Endometritis and vaginitis ( (L.f.) J.H.Ross Infectious diseases in cattle (van der Merwe, Verdoorn Used medicinally for cattle ( (Sond.) R. & A. Fernandes Abdominal problems in animals ( (Vahl) Soland. Ex Roem. (L.f.) Herb. Redwater in cattle, constipation in cattle, used (A. Rich.) Hochst. Diarrhoea, fractures ( Thunb. Leaves applied in hot fomentations to goats Hook. F. Used medicinally for cattle ( L.f. Diarrhoea, gallsickness ( L.f. Roots given to livestock as treatment for shock Rhus lancea Rhus incisa Sclerocarya birrea Boophane disticha Protorhus longifolia Crinum delagoense Haemanthus albiflos Crinum moorei Ozoroa paniculosa Agapanthus praecox Exomis microphylla Ammocharis coranica Zantedeschia albomaculata Heteromorpha trifoliata Zeyh. Hypoestes aristata & Schult. Secamone filiformis Acokanthera oppositifolia Strophanthus speciosus Reber Cussonia spicata Anacardiaceae Anacardiaceae Anacardiaceae Amaryllidaceae Anacardiaceae Amaryllidaceae Amaryllidaceae Amaryllidaceae Anacardiaceae Alliaceae Amaranthaceae Amaryllidaceae Araceae Apiaceae FamilyAcanthaceae Species Indication Plant part used Chemical constituents Screened for activity Table 1 Plants used in South Africa for ethnoveterinary purposes, and bioactivity of tested species Apocynaceae Apocynaceae Apocynaceae Araliaceae

4 L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx Naidoo et ) ); Naidoo et al., ) ); anti-babesial ( Luseba et al., 2007 Luseba et al., 2007 al., 2005 anti-rickettsial ( 2006 anti-inflammatory, mutagenic ( anti-inflammatory, mutagenic ( ) ) Graham et Hutchings et al., 1996 phenylheptatriyne and chalcones ( al., 1980; Hoffman and Hoelzl, 1988 emodin, aloenin, polysaccharides, lectins and other compounds ( Rhizome decoctions Rhizome decoctions Unspecified parts Fresh leaves, roots, whole plant Leaves Leaves, roots, whole plant Smoke from burning leaves Leaves, juice from leaves Roots Stems, aerial partsTubers Roots Roots, tubers Root infusions or decoctions Antibacterial, Leaves Antibacterial, Leaf infusions ) ) Leaf decoctions Aloin, barbaloin, aloe ); ) ) Unspecified The polyacetylene ); ) Whole plant ) )Stem Dold and )Roots Jacot Watt and Van der Merwe Van der Merwe Hutchings et al., Hutchings et al., Van der Merwe Luseba and Van der ); redwater, intestinal ) Hutchings et al., 1996 Dold and Cocks, 2001 ) Van der Merwe et al., ) Hutchings et al., 1996 Luseba and Van der Merwe, Hutchings et al., 1996 Luseba and Van der Merwe, Dold and Cocks, 2001 ) Dold and Cocks, 2001 Dold and Cocks, 2001 Dold and Cocks, 2001 Dold and Cocks, 2001 ) Watt and Breyer-Brandwijk, 1962 ); gallsickness, parasites, diarrhoea, ) ) ) ) Masika et al., 2000 Dold and Cocks, 2001 ); Burns, general ailments, blood cleansing, ) ) ) ) Dold and Cocks, 2001 Van der Merwe et al., 2001 1996 Guillarmod, 1971 et al., 2001 2006 internal parasites, eye infections ( 1996 intestinal parasites ( Burns, general ailments, blood cleansing, internal parasites, eye infections ( 2001 cattle ( worms ( improper food ( et al., 2001 sores, redwater, uterine infections ( et al., 2001 Cocks, 2001 galactagogue in cows ( wounds and maggots ( 2006 ( Breyer-Brandwijk, 1962 Merwe, 2006 constipation, retained placenta, dystocia, maggots ( indigestion in poultry ( (Schönland) H.F.Glen (Kunze) Kuntze Retained placenta in cows by the Sotho ( (Bak.) Oberm. Anthelmintics for animals and humans ( (L.) R. Br. Stems used to encourage lactation in cows, (L.) Willd. Used to treat sick cattle and goats ( (Burch.) Oberm. Retained placenta in cows ( davyana (L.f.) O.Hoffm. Heartwater in goats ( (L.f.) J.H. Ross Diarrhoea in cattle ( Burch. Sores, redwater, uterine infections ( (Kunth) Oberm. Used to treat livestock for shock after an accident Jacq. Wash to treat footrot in sheep and goats ( Mill. Used to drench sick calves ( (L.) Willd. Redwater in cattle ( var. All. Used for ‘blood scours’ in calves and enteritis and Berger Newcastle disease in chickens ( L. Equine anthelmintics ( Bak. Used to protect cattle from the ill effects of eating Baker Wounds and maggots ( Haw. Retained placenta in cows, tapeworm, redwater, sp. Administered to horses with bots ( Mill. Typhoid, ticks and lice in poultry, redwater in Bidens pilosa Arctotus arctotoides Polystichum Dryopteris athamantica Bulbine alooides Bulbine asphodeloides Aloe zebrine Aloe maculata Aloe tenuior Secamone filiformis Asparagus laricinus & D.S.Hardy Aloe cooperi Aloe ferox Aloe greatheadii Sarcostemma viminale Asparagus setaceus Asparagus suaveolens Protasparagus virgatus Aloe arborescens Phoenix reclinata Aloe marlothii ) Continued Asteraceae Asteraceae Aspidiaceae Aspidiaceae Asphodelaceae Asphodelaceae Asphodelaceae Asphodelaceae Asphodelaceae Asclepiadaceae Asparagaceae Asphodelaceae Asphodelaceae Asphodelaceae Asclepiadaceae Asparagaceae Asparagaceae Asparagaceae Asphodelaceae Table 1 ( FamilyArecaceae Species Indication Plant part used Chemical constituents Screened for activity Asphodelaceae

L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx 5 McGaw ) ); antibacterial, Luseba et al., 2007 brine shrimp toxicity ( et al., 2007 anti-inflammatory, mutagenic ( ) ) 17 ). Hutchings et Zdero and ) Candy et al., ) and 3-hydroxy- Bohlmann and ) ) ) -coumarate ( Bohlmann and Zdero, 1978b Bohlmann et al., 1983 Dictionary of Natural Dekker et al., 1987 Bohlmann and Fritz, 1979 al., 1996 Epi-friedelinol and C atractyligenin ( 1977 angeloyl and bisabolenes ( vernodalin from aerial parts, and 13-hydroxybisabol-2,10- dien-1-one and small amounts of onopordopicrin in roots ( Onopordopicrin ( Bohlmann, 1987 Zdero, 1978a The alkaloids stachydrine ( Products, 1996 4-methoxy-3-methyl-oxindole ( p acetylenic compounds ( Infusions from leaves and stems Root decoctions Germacranolides ( Roots Root decoctions Root paste Atractyloside and its aglycone, LeavesUnspecified parts Stems Roots, leaves A tricyclic sesquiterpenoid, Squalene,Leaves vernolide and Leaves Dried leaf milk infusions Aerial parts Antibacterial, anthelmintic, Paste made from root ashes, root infusions and decoctions Unspecified )Roots ) Roots Matricaria ester and ) ), ) Gerstner, Watt and Gerstner, Hutchings et al., Gerstner, 1939 Gerstner, 1939 ) ) ); pounded leaf ) ) Hutchings et al., Hutchings et al., Dold and Cocks, Dold and Cocks, Luseba and Van der Watt and Van der Merwe et al., ) ) Van der Merwe et al., 2001 Mabogo, 1990 Watt and Breyer-Brandwijk, ) ) ) ) ) ); fractures ( ); root decoctions administered by ) ) Watt and Breyer-Brandwijk, 1962 Gerstner, 1939 Hutchings et al., 1996 Hutchings et al., 1996 Dold and Cocks, 2001 1996 Tonics for stock animals ( ( plants used for sores and woundshorses on ( 1962 ( 2001 and root infusions administered by Vhavenda as anthelmintics to domestic animals ( 1996 Breyer-Brandwijk, 1962 2001 1939 Lobedu as anthelmintics to donkeys ( Diarrhoea in cattle ( Merwe, 2006 1996 2001 Diarrhoea in lambs ( ( heartwater ( root decoction for gallsickness in stock ( cows; root infusions used for stomach ailments in animals, particularly diarrhoea in cattle ( Breyer-Brandwijk, 1962; Pujol, 1990 1939 Hilliard Used by Zulus to treat calves ( (Less.) B.L. Less. Heartwater in goats ( (Lam.) Phill. & (Thunb.) DC. Used for treating calves ( DC. Anthelmintics for calves, sheep and goats Lam. Root ash paste applied to sore teats in DC. Swellings in animals ( (Lam.) Thell. Eye infections, pneumonia, diarrhoea, DC. Used to kill maggots in cattle ( DC. Plants used for horse sickness ( L. Used by Xhosa for gallsickness in stock DC. Anthrax and ‘quarter evil’ in cattle Sond. Gallsickness in stock animals; powdered Less. Used for treating calves ( (Thunb.) Druce Gallsickness in cattle ( Microglossa mespilifolia Robinson Capparis sepiaria Capparis tomentosa Dicoma anomala Senecio tamoides Vernonia mespilifolia Vernonia neocorymbosa Balanites maughamii Ehretia rigida Senecio oxyriifolius Schweick. Callilepis laureola Brachylaena ilicifolia Brachylaena elliptica Schkuhria pinnata Brachylaena discolor Printzia pyrifolia Mikania capensis ) Continued Asteraceae Capparaceae Capparaceae Asteraceae Asteraceae Asteraceae Asteraceae Balanitaceae Boraginaceae Asteraceae Asteraceae Asteraceae Asteraceae Asteraceae FamilyAsteraceae Species Indication Plant part used Chemical constituents Screened for activity Table 1 ( Asteraceae Asteraceae

6 L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx ) Masika and Afolayan, 2002 Antibacterial, antifungal ( ) ) Hutchings Hutchings Watt and ) ) Watt and Watt and ) flavonoids, ) ) ) Hutchings et al., 1996 Watt and Hutchings et al., 1996 Breyer-Brandwijk, 1962 quercetin, oxalic, malic and succinic acids, triterpenoid glycosides, chenopodoside A and B, amino acids, ascaridole ( et al., 1996 ( potassium oxalate, ascorbic acid, sitosterol, oleanic acid ( Breyer-Brandwijk, 1962; Hutchings et al., 1996 acid, various alkaloids and other constituents ( An alkaloid and organic acids ( Breyer-Brandwijk, 1962 Dulcitol, a spermidine alkaloid, celacinnine, triterpenoids, maytansine ( et al., 1996 Diosgenin ( Breyer-Brandwijk, 1962 Root bark Leaves, roots Unspecified Toxic cucurbitacins Unspecified Hydrocyanic acid, Milk or whey bark infusions Unspecified Saponins ( squeezed leaves CormsRoots Colchicine, chelidonic Water heated in scooped out tuber Bark and leaf infusions Bark Lotions from boiled crushed inner parts of tubers ) ) ); ) Bark ) Hutchings ) ) ) Bark ) )Roots ) ) ) Drops from ) Gerstner, 1939; administered to goats Hutchings et al., 1996 Dold and Cocks, 2001 administered to goats and Hutchings et al., 1996 Luseba and Van der Merwe, Masika et al., 2000 ) Van der Merwe et al., 2001 Van der Merwe et al., 2001 Watt and Breyer-Brandwijk, 1962 ) Van der Merwe et al., 2001 Dold and Cocks, 2001 Luseba and Van der Merwe, 2006 Watt and Breyer-Brandwijk, 1962 Watt and Breyer-Brandwijk, 1962 ) Watt and Breyer-Brandwijk, 1962 Watt and Breyer-Brandwijk, 1962 et al., 1996 ( Roberts, 1990 dogs ( and screw-worm on cattle ( 2006 Xhosa ( diarrhoea ( diarrhoea ( Chenopodium ambrosioides and sheep for anaemia ( Chenopodium album sheep for anaemia ( ( parasites ( (Burch.) Sond. Small doses administered as fattening tonics to L. Decoctions made from plants mixed with (Thunb.) Loes. Heartwater in cattle, worms in calves, intestinal Vent. Fertility problems ( (Eckl. & Zeyh.) N.K.B.Robson Administered by Zulus to stock animals for (Burtt Davy) Codd Diarrhoea ( L. Decoctions made from plants mixed with (Eckl. & Zeyh.) Kuntze Conjunctivitis ( (Kunth) Dur. & Schinz Sores and wounds in animals and humans by Hallier f. Fractures ( (Kunth) Eckl. Swollen udders and uterine problems in cows Thunb. Used by Zulus to drench worm-infested calves L.f. Used as animal medicines by the Xhosa ( Burch. Ex DC. Wounds ( L. Used to kill lice, for skin eruptions, tick infections (Burm. F.) C.A.Sm. Heartwater in cows ( Curtisia dentata Cucumis africanus Cassine aethiopica Terminalia sericea Dioscorea dregeana Seddera sufruticosa Maytenus heterophylla Chenopodium ambrosioides Cassine transvaalensis Combretum caffrum Combretum erythrophyllum Gloriosa superba Combretum paniculatum Dioscorea sylvatica Chenopodium album Mystroxylon aethiopicum ) Continued Cornaceae Cucurbitaceae Table 1 ( FamilyCelastraceae Species Indication Plant part used Chemical constituents Screened for activity Combretaceae Dioscoreaceae Convolvulaceae Celastraceae Chenopodiaceae Celastraceae Combretaceae Combretaceae Colchicaceae Combretaceae Dioscoreaceae Chenopodiaceae Celastraceae

L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx 7 McGaw McGaw Naidoo et ) ) Naidoo et al., ); antibacterial, ) ) ); anti-babesial ( Luseba et al., 2007 Luseba et al., 2007 Antibacterial, anthelmintic, brine shrimp toxicity ( et al., 2007 anti-inflammatory, mutagenic ( anti-inflammatory, mutagenic ( brine shrimp toxicity ( et al., 2007 al., 2005 Anti-rickettsial ( 2006 ) ) ) Trease and ). Hutchings et al., Watt and Watt and ) Hutchings et al., 1996 lipases and ricinine ( Evans, 1983 Tannin ( Breyer-Brandwijk, 1962 ( Breyer-Brandwijk, 1962 1996 Sap, wood Powdered seed Seeds contain a fixed oil, ricin, Bark Roots, aerial parts and bulb Aerial parts Unspecified parts The alkaloid oroboidine Aerial parts RootsRoots, bark Antibacterial, Saponins ( Bark Milk infusions of leaves, stems and roots Seeds Unspecified parts Alkaloids ( Leaf sap Leaves, roots Bark, leaves Milky latex Antibacterial, anthelmintic, ) ) Branch tips ) ) Bark decoction ), root Dold and Luseba Luseba and Watt and Dold and ); Mfengu Luseba and ) ) ) ) Dold and Cocks, ) Van der Merwe et ); sweating ) ) ) Luseba and Van der Luseba and Van der ) Hutchings et al., Masika et al., 2000 ) Van der Merwe et al., Luseba and Van der ); diarrhoea, heartwater, ) ) ) ); fractures and diarrhoea Van der Merwe et al., 2001 Van der Merwe et al., 2001 ) Luseba and Van der Merwe, 2006 Hutchings et al., 1996 Bryant, 1966 ); heartwater, blackquarter, appetite ) ); constipation, internal parasites Hutchings et al., 1996 Van der Merwe et al., 2001 Watt and Breyer-Brandwijk, 1962 Gerstner, 1939 Hutchings et al., 1996 Van der Merwe et al., 2001 Van der Merwe et al., 2001 sickness ( ( refusing to suckle ( 1996 ( and Van der Merwe, 2006 The Xhosa use roots for diarrhoeadysentery and in cattle, horses and humans ( given to cows for mange ( Merwe, 2006 2001 stimulant or tonic ( coughing, pneumonia ( al., 2001 Eye infections ( 2001 on maggot-infested sores on cattle ( goats ( Merwe, 2006 sores ( Van der Merwe, 2006 goats ( use bark for colds in horsesBreyer-Brandwijk, 1962 ( ( For milk production ( Merwe, 2006 Pneumonia, tonic, fertility enhancement ( and goats for conjunctivitis ( Cocks, 2001 Cocks, 2001 ( goats, sheep, poultry and pigs ( Eye infection, blackquarter ( Van der Merwe, 2006 (Burch.) (L.) Druce Fresh leaf sap applied to eyes of sheep Hochst. Ex A. (Boiss.) L.C. Sond. Sap applied to cattle sores to kill maggots Müll.Arg. [and Sond.] (E. Mey.) Presl Powdered roots used by Zulus to fatten Burch. var. N.E.Br. ex A.Berger Blackquarter ( L. Administered as a purgative to calves Oliv. Drench for worm infestations ( Willd. Hastens oestrus ( Harv. The Sotho use plant infusions topically Sond. General ailments, diarrhoea ( (Ait.) Benth. Zulus use plant to destroy maggots in L. Drenches for griping pains in calves L. Drench for constipation in cattle and Hayne Diarrhoea in goats, intestinal parasites in (Forssk.) Hayne Diarrhoea ( Spirostachys abbrevia Elephantorrhiza elephantina Skeels Ricinus communis Cassia abbreviata Phyllanthus burchellii Phyllanthus parvulus Jatropha curcas Calpurnia aurea Calpurnia villosa Adenopodia spicata Clutia pulchella Croton gratissimus Jatropha zeyheri DC. gratissimus Diospyros mespiliformis Euphorbia cooperi Acacia tortilis Sansevieria hyacinthoides Synadenium cupulare Wheeler Acacia decurrens Acacia karroo ) Continued Euphorbiaceae Fabaceae Euphorbiaceae Fabaceae Euphorbiaceae Euphorbiaceae Fabaceae Fabaceae Fabaceae Euphorbiaceae Euphorbiaceae Euphorbiaceae Ebenaceae Euphorbiaceae Fabaceae FamilyDracaenaceae Species IndicationEuphorbiaceae Plant part used Chemical constituents Screened for activity Fabaceae Table 1 ( Fabaceae

8 L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx ) ) McGaw McGaw ) Bizimenyera et ) ); antibacterial, Masika and Afolayan, 2002 Luseba et al., 2007 ( Antibacterial, anthelmintic, brine shrimp toxicity ( et al., 2007 brine shrimp toxicity ( et al., 2007 anti-inflammatory, mutagenic ( anthelmintic ( al., 2005, 2006a, 2006b ) Watt ) ) ) Watt and Wagner Wagner Watt and ) ) Watt and ) Watt and Breyer-Brandwijk, ( 1962 and Bladt, 1975 Coumarins in roots ( and Bladt, 1975 and Breyer-Brandwijk, 1962 erythrophleine ( Breyer-Brandwijk, 1962 Breyer-Brandwijk, 1962 deguelin ( Breyer-Brandwijk, 1962 Unspecified parts Roots may contain a saponin Bark, roots Bark decoction Antibacterial, antifungal Bark Antibacterial, anthelmintic, Warm water leaf and stalk infusions Bark, root bark Antibacterial, antioxidant, Roots Root bark decoctions Leaf infusions Coumarins in roots ( Decoctions of unspecified parts Unspecified Bark Seeds and bark contain Unspecified partsRoot decoction Phloroglucin tannin ( Roots, seeds, leaves Roots contain toxicarol and Cold water leaf infusions Roots Bitter principle, celastrin ( Unspecified ); ) ) ) ) ) Hutchings et Luseba and ) Watt and Gerstner, 1941 ) Gerstner, 1939 ) Watt and ) ) Luseba and Van ) ); gallsickness, Hulme, 1954 Dold and Cocks, ) Dold and Cocks, Sond. ( Van der Merwe et al., ) Van der Merwe et al., 2001 Gerstner, 1938 Watt and Breyer-Brandwijk, Hulme, 1954 ) Dold and Cocks, 2001 Bryant, 1966 Hutchings et al., 1996 ) ) ) ) Doke and Vilakazi, 1972 Watt and Breyer-Brandwijk, 1962 against quarter-evil and other diseases ( Van der Merwe, 2006 intestinal diseases, heartwater, anthrax, pneumonia ( Merwe, personal communication) 2001 2001 der Merwe, 2006 udders after calving ( worms, blackquarter ( 2001 especially roundworm ( Breyer-Brandwijk, 1962 al., 1996 on animals and humans ( Ziziphus zeyheriana leaf extracts used as anthelmintics for cattle ( Breyer-Brandwijk, 1962 in animals and women ( humans ( succession of calves of the same( gender dogs ( in cattle, liver disorders in cattlesheep and ( humans ( 1962 to cows ( Corbishley Lung sickness in cattle and abortions in Sond. Tonic, diarrhoea ( Curtis Diarrhoea in goats and cows, heartwater DC. General illness, gallsickness, intestinal C.B. Cl. Administered by the Zulus as purgatives (L.f.) L’Hérit Stomach ailments in calves, lambs and (E. Mey.) Harv. Roots and seeds used for killing vermin (E. Mey.) Verdc. Administered to cows with swollen (Andr.) Sweet Administered to sick calves ( DC. Used as anthelmintics for calves with Meisn. Plants used by Zulus for protecting cattle DC. Diarrhoea in calves ( Sond. Infectious diseases in cattle (van der L.f. Anthelmintics in animals and humans, (Hook. F.) Jessop Administered to cows to ensure a L. Used to facilitate expulsion of afterbirth Jacq. Redwater in cattle ( Mill. Diarrhoea and gallsickness ( sp. Purgative and vermifuge for animals and Tephrosia kraussiana Senna italica Schotia brachypetala Schotia latifolia Pterocarpus angolensis Peltophorum africanum Macrotyloma axillare Indigofera sessilifolia Albuca Ledebouria cooperi Erythrophleum lasianthum Indigofera frutescens Pelargonium luridum Pelargonium reniforme Pelargonium sidoides Tephrosia macropoda Monsonia emarginata Streptocarpus prolixus Gunnera perpensa ) Continued Fabaceae Fabaceae Fabaceae Fabaceae Fabaceae Fabaceae Fabaceae Fabaceae Fabaceae Hyacinthaceae Hyacinthaceae Table 1 ( FamilyFabaceae Fabaceae Species Indication Plant part used Chemical constituents Screened for activity Geraniaceae Geraniaceae Geraniaceae Geraniaceae Gesneriaceae Gunneraceae

L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx 9 Naidoo et al., ) 2005 ) Dictionary ) -pyrones ␣ Dictionary of Natural Volatile oil and diterpenoids related diterpenoids, large amounts of ( Products, 1996 (labdane type lactones) for example marrubin ( of Natural Products, 1996 Corms Bark, leaves Bulb decoction BulbsUnspecified Anti-babesial ( Bulbs, leaves Unspecified Ground rhizomes Roots, leaves, drops from squeezed leaf used for eyes Leaves A diterpene diol, ibozol, and Bark infusion Leaves Bark infusion Powdered aerial parts Roots, leaves Leaves Leaves ) Unspecified ) ) ); Dold Dold ) ); bulb Watt ) ); used by Hutchings ) Unspecified ) Dold and Gerstner, 1941 ) Watt and ) ) Van der Merwe et Dold and Cocks, Dold and Cocks, Dold and Cocks, Gerstner, 1938 ); eye inflammation ) ) ) Hutchings et al., 1996 Hulme, 1954 ) ) Gerstner, 1941 ) Dold and Cocks, 2001 Van der Merwe et al., 2001 ) Hulme, 1954 Hulme, 1954 ) ) ) Watt and Breyer-Brandwijk, 1962 Masika et al., 2000 Watt and Breyer-Brandwijk, 1962 Hutchings et al., 1996 Hutchings et al., 1996 ( worms in cattle ( Fertility enhancement, general ailments, heartwater, abortion ( al., 2001 afterbirth ( internal parasites, gallsickness, heartwater, redwater, sores, retained placenta ( the Xhosa to prevent or treatailments stomach in goats and sheep ( drinking water to prevent sickness in poultry and are used for gallsicknesscattle in ( ( and Johnson, 1986 Cocks, 2001 ( infusion for diarrhoea in goats, leaf decoction for gallsickness ( ( and Breyer-Brandwijk, 1962 and Cocks, 2001 and Cocks, 2001 and sheep, bloat in goats, anthrax ( Used for gallsickness and fevers in( cattle drinking water to prevent sickness in poultry and are used for gallsicknesscattle in ( 2001 Breyer-Brandwijk, 1962 2001 2001 Baker] Fisch. & C.A. Benth. Drenches for animals ( (Klatt) Goldbl. Used for bovine diarrhoea by the Sotho Gilg. Heartwater and diarrhoea in cattle ( Thunb. Gallsickness in cattle, heartwater in goats (Pappe) Roundworm in cows ( (L.f.) Jessop Gallsickness in animals by the Xhosa Bak. Diarrhoea in calves by the Sotho ( L. Gallsickness in stock ( E. Mey. Ex Arn. Purgatives for calves ( (Burm. F.) Iwarsson Pounded roots and leaves are added to Schinz General ailments, intestinal diseases, (Jacq.) Bak. ‘Itch’ in goats ( (L.) R. Br. Pounded roots and leaves are added to (L.f.) Baker Intestinal parasites in cattle, retained (L.) Sweet ex Klatt Tonics for goats ( Planch. Administered to cattle with lung sickness (Benth.) Engl. Gallsickness in stock ( (Burch.) Jessop Used as purges for calves ( Hypoxis rigidula Apodytes dimidiata Crocosmia paniculata Hypoxis hemerocallidea Mey. [and Urginea physodes Urginea sanguinea Dietes iridioides Urginea altissima Ledebouria revoluta Scilla natalensis Scilla nervosa Leonotis leonurus Watsonia densiflora Leonotis ocymifolia Strychnos decussata Strychnos henningsii Teucrium africanum Tetradenia riparia Leucas capensis Marrubium vulgare Plectranthus laxiflorus ) Continued Icacinaceae Iridaceae Hypoxidaceae Hyacinthaceae Htacinthaceae Iridaceae Hyacinthaceae FamilyHyacinthaceae SpeciesHyacinthaceae Hyacinthaceae Indication Plant part used Chemical constituents Screened for activity Lamiaceae Iridaceae Table 1 ( Lamiaceae Loganiaceae Loganiaceae Lamiaceae Lamiaceae Lamiaceae Lamiaceae Lamiaceae

10 L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx McGaw ) ); antibacterial, Luseba et al., 2007 Antibacterial, anthelmintic, brine shrimp toxicity ( et al., 2007 anti-inflammatory, mutagenic ( ) ) ) Moreno and Watt and ) Hutchings et al., Watt and ) Hutchings et al., 1996 Breyer-Brandwijk, 1962 as yiamoloside B ( Rodriguez, 1981 dried leaves contain many constituents ( 1996 ( Breyer-Brandwijk, 1962 Leaf, root or bark decoction Leaf decoctions Anthraquinones ( Leaf decoction Aerial parts, roots, Root infusions Triterpenoid saponins, known Root infusions Unspecified Roots Roots Leaves, bark Fruit Root decoction Powdered leaves Essential oils from ground Leaves, bark, roots Bark may contain tannin Bark decoctions Bark whole plant Bark decoctions Tannin ( )Roots ) ) )Roots Dold ) Bark decoction ) Unspecified parts Watt and Watt and Jacot Hutchings et al., Watt and ) ) ) ) and Vhavenda Hutchings et al., ) Watt and Dold and Cocks, Dold and Cocks, ) Van der Merwe et al., Dold and Cocks, 2001 Van der Merwe et al., ) ) ) ) Masika et al., 2000 Van der Merwe et al., 2001 Jacot Guillarmod, 1971 Watt and Breyer-Brandwijk, 1962 Watt and Breyer-Brandwijk, 1962 ) ) ) ) ) ) ); Vhavenda use root decoctions for Dold and Cocks, 2001; Masika et al., Luseba and Van der Merwe, 2006; Van Gerstner, 1941 Masika et al., 2000 Mabogo, 1990 1996 Distemper in dogs, gallsickness in cattle ( 2000 2001 Distemper in dogs ( Dystocia, drench for retained placenta ( der Merwe et al., 2001 Breyer-Brandwijk, 1962 cattle ( Emetics for animals and humans ( Gall sickness in animals ( Guillarmod, 1971 Retained placenta, intestinal worms ( Internal parasites ( 2001 vaginitis in cows, bark infusion for diarrhoea in goats, gallsickness in cattle, eye lotion for animals and humansand ( Cocks, 2001 2001 cattle ( Breyer-Brandwijk, 1962 Breyer-Brandwijk, 1962 2001 production by Zulus ( Breyer-Brandwijk, 1962 ( bovine galactagogues ( 1996 retained placenta in cows ( DC. Retained placenta ( (Dcne.) microphylla (Steud.) Stapf Sims Gallsickness ( E.Mey. ex Harv. (L.) Mez Heartwater in cows ( Harv. Drench for stock animals ( Retz. The Xhosa use roots for lung sickness in Lam. Diarrhoea in cows ( (Thunb.) R. Br. Ex Presl Anthrax ( L. Lung sickness in cattle ( (Thunb.) R. Br. Ex L. Pneumonia ( L. var. Oliv. Used by the Xhosa for gallsickness in (R. Br. Ex Lindl.) H. Steinh. Threadworm in horses ( L. Leaves used for endometritis and Dicerocaryum senecioides (Miq.) Miq. Administered to cows to increase milk Forssk. Zulus use leaf and bark infusions as Polygala hottentotta Emex australis Podocarpus latifolius Mirb. Mirb. Plumbago zeylanica Podocarpus falcatus Pittosporum viridiflorum Dicerocaryum eriocarpum J.Abels [and (Kltzsch.) J.Abels] Plumbago auriculata Phytolacca heptandra Phytolacca octandra Olea europaea Eulophia speciosa Bol. Cymbopogon marginatus ex Burtt Davy Hibiscus malacospermus & Sond. Bersama tysoniana Ximenia americana Harpagophytum procumbens Rapanea melanophloeos Ficus ingens Heteropyxis natalensis Ficus sur ) Continued Polygalaceae Polygonaceae Podocarpaceae Plumbaginaceae Podocarpaceae Pittosporaceae Pedaliaceae Plumbaginaceae Phytolaccaceae Phytolaccaceae Oleaceae Orchidaceae Poaceae Table 1 ( FamilyMalvaceae Melianthaceae Species Indication Plant part used Chemical constituents Screened for activity Olacaceae Pedaliaceae Myrsinaceae Moraceae Myrtaceae Moraceae

L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx 11 ) McGaw McGaw McGaw ) ) ); antibacterial, ) Luseba et al., 2007 Masika and Afolayan, 2002 brine shrimp toxicity ( et al., 2007 brine shrimp toxicity ( et al., 2007 anti-inflammatory, mutagenic ( Antibacterial, anthelmintic, brine shrimp toxicity ( et al., 2007 Antibacterial, antifungal ( ) ) ) ); timber Watt and Hutchings Watt and Watt and ) ) Watt and Breyer-Brandwijk, Hutchings et al., 1996 has high oil and resin content ( 1962 Contains anemonol ( Breyer-Brandwijk, 1962 and induces sneezing ( volatile oil ( Breyer-Brandwijk, 1962 Resinous and oily substances in wood and leaves ( Breyer-Brandwijk, 1962 alkaloids, coumarins and many other compounds ( et al., 1996 Root-stock Leaf decoctions, roots Infusions from shoots and leaves Bark Antibacterial, anthelmintic, Roots, leaves Antibacterial, anthelmintic, Wood Powdered wood is irritating Root bark decoctions Decorticated root infusions Unspecified parts Chrysophanic acid, emodin and Leaf and root infusions or decoctions, leaf sap, bark Root decoctions Bark infusionsLeaves, root decoction Root decoctions Terpenoid hydrocarbons, of unspecified parts ) Root ) Decoction or infusion ) Van Dold ) ); root Dold ) ) ); leaf sap Jacot A. DC. to treat ); bark used for ) ) ) Dold and Cocks, Hutchings et al., Masika et al., 2000 Dold and Cocks, 2001 ) ) ) Hutchings et al., 1996 Euclea coriacea Van der Merwe et al., 2001 Watt and Breyer-Brandwijk, Watt and Breyer-Brandwijk, Hutchings et al., 1996 Hutchings et al., 1996 ) ) ) Hutchings et al., 1996 Hutchings et al., 1996 Watt and Breyer-Brandwijk, 1962 Watt and Breyer-Brandwijk, 1962 kid goats, roots for broken bones ( and Cocks, 2001 Used by Xhosa to aid expulsionretained of animal or human placenta ( Merwe, personal communication) der Merwe et al., 2001 ailments ( ( diarrhoea ( humans ( 1962 gallsickness in stock animals ( Guillarmod, 1971 ( mucus from noses of sheep and( goats infusions given to stock animals with coughs ( used for inflamed eyes in animalshumans and ( 1962; Masika et al., 2000 heartwater and diarrhoea in cattle ( and Cocks, 2001 Dysentery in cattle ( 1996 2001 humans ( prunelloides (L.f.) Radlk. Leaf and root infusions used to clear (Klotzsch ex (Thunb.) Radlk. Anthrax remedy, for ticks in cattle (Thunb.) Harv. Gallsickness in stock ( Sond. Diarrhoea, internal parasites, general Willd. Fertility enhancement, sores, burns ( (Verdoorn) Waterm. Administered as tonics to animals and Thunb. Used with Thunb. Vermifuge and for bots in horses Lam. Dystocia in cows ( Engl. Dysentery and diarrhoea in calves and (Sond.) Grubov Infectious diseases in cattle (van der (Willd.) Hook. F. Ex (L.) Batsch. Leaf decoction for diarrhoea in lambs and Meisn. Enemas given to calves with bloody L. spp. Retained placenta ( Prunus persica Pentanisia prunelloides Eckl. & Zeyh.) Walp. subsp. Clematis brachiata Berchemia zeyheri Ziziphus mucronata Ziziphus zeyheriana Protea welwitschii Ptaeroxylon obliquum Rumex lanceolatus Protea caffra Clausena anisata Benth. Zanthoxylum davyi Salix Azima tetracantha Hippobromus pauciflorus Zanthoxylum capense ) Continued Rosaceae Rubiaceae Ranuncluaceae Rhamnaceae Rhamnaceae Rhamnaceae Proteaceae Ptaeroxylaceae Proteaceaae FamilyPolygonaceae Species Indication Plant part used Chemical constituents Screened for activity Table 1 ( Rutaceae Rutaceae Salicaceae Salvadoraceae Sapindaceae Rutaceae

12 L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx McGaw McGaw ) ) brine shrimp toxicity ( et al., 2007 brine shrimp toxicity ( et al., 2007 ) Watt ) ) ) Hutchings et Hutchings et al., Watt and and references ) Hutchings et al., 1996 Oliver-Bever, 1986 Breyer-Brandwijk, 1962 azosolanidin, quinhydrone solasonine, solasodine, solasodamine from fruit ( and Breyer-Brandwijk, 1962 leucanthocyanidins from bark ( hyoscyamine and hyoscine ( choline, tropanaol, glycowithanolides, withanolides, withaferine and withasomnine ( al., 1996 therein) toxic diterpenoid fraction, polysaccharides daphnane orthoesters ( 1996 Fruit Fruit, leavesAerial Solanin, parts solanidine, Fruit Solanine ( Unspecified parts Roots Unspecified parts; bark Cinnamic acid, kaempferol and Powdered leavesLeaves Alkaloids including Unspecified parts, roots Many compounds including Roots Leaves and flowers Antibacterial, anthelmintic, Root decoction Antibacterial, anthelmintic, Unspecified parts Flavone heteroside from roots, )Roots ) ) Fruit sap Watt ) ) )Roots Luseba ) Dold and ) ) Hutchings et Hutchings et ); infectious Van der Merwe et Van der Merwe et Luseba and Van Van der Merwe et ); roots used for Dold and Cocks, 2001 ) ) Van der Merwe et al., Hutchings et al., 1996 ) Van der Merwe et al., 2001 Dold and Cocks, 2001 Watt and Breyer-Brandwijk, ) ) ) ); Xhosa use bark for gallsickness ); diarrhoea ( Jacot Guillarmod, 1971 Van der Merwe et al., 2001 Gerstner, 1941 Watt and Breyer-Brandwijk, 1962 ) ); bark decoction used for redwater Watt and Breyer-Brandwijk, 1962 Gerstner, 1939 ringworm in animals and humans, fruit sap for sores, distemper and soredogs eyes ( in sheep and horses by Xhosa and( Sotho der Merwe, 2006 for anthrax ( ( Fertility enhancement ( al., 2001 tonics to calves and goats ( animal and human bruises and wounds to draw out inflammation and pusand ( Breyer-Brandwijk, 1962 2001 al., 1996 in stock ( 1962 in cattle ( cows ( al., 1996 black gallsickness in cattle ( al., 2001 and Van der Merwe, 2006 diseases in cattle (van der Merwe, personal communication) fractured limbs of stock animals bySotho the ( al., 2001 Cocks, 2001 E. Mey. Diarrhoea ( Scop. Dystocia in cows ( Willd. Respiratory problems ( (Hochst.) Planch. Newcastle disease in chickens ( Dun. Ringworm in cattle and horses and also (L.) Dun. Used to stimulate milk production in L. Powdered leaves are applied by Zulus to Dun. Fruit sap and leaf paste used for sores on L. Preparations administered by Zulus as L. Eye infections ( L. Sores ( Meisn. Preparations injected near the site of L. Fruit pulp used by Xhosa for warts and Eckl. & Zeyh. Used medicinally by Zulus for calves L.f. Heartwater in cows, anthrax ( DC. Fertility enhancement ( Solanum hermannii Solanum capense Solanum mauritianum Solanum incanum Solanum panduriforme Solanum lichtensteinii Datura stramonium Nicotiana tabacum Englerophytum magalismontanum Krause Sideroxylon inerme Solanum aculeastrum Pappea capensis Withania somnifera Dombeya rotundifolia Gnidia capitata Gnidia kraussiana Grewia flava ) Continued Solanaceae Solanaceae Solanaceae Solanaceae Solanaceace Solanaceae Solanaceae Solanaceae Sapotaceae Sapotaceae Solanaceae Table 1 ( FamilySapindaceae Species IndicationSolanaceae Plant part used Chemical constituents Screened for activity Sterculiaceae Thymelaeaceae Thymelaeaceae Tiliaceae

L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx 13 McGaw McGaw ) Naidoo et al., ); antibacterial, ) ) Luseba et al., 2007 Antibacterial, anthelmintic, brine shrimp toxicity ( et al., 2007 anti-inflammatory, mutagenic ( 2005 brine shrimp toxicity ( et al., 2007 ). ) ) -terpineol ␣ Hutchings et al., -dimethyl ether Watt and ) -glucoside from leaf Van Wyk et al., 1997 Hutchings et al., 1996 and other monoterpenoids ( sesquiterpenoid, triterpenoids ( 1996 lantanin ( Breyer-Brandwijk, 1962 4 ( Roots Whole plant, aerial parts Rhizome infusions Volatile oil with a characteristic Aerial parts A steroidal mixture and Rootstock Leaves Leaves Root bark Unspecified parts Quercetin 3 Tubers Anti-babesial ( Leaves, bark Leaves Volatile oil and the alkaloid Roots, leaves, stems Antibacterial, anthelmintic, ); ) ) Tubers ) ), ). The Watt and Dold and Van der ); diarrhoea in Watt and Van der Merwe Watt and ) ) ). The Tswana use ) Watt and ) ) Dold and Cocks, Van der Merwe et al., ) Dold and Cocks, 2001 Hutchings et al., 1996 Pujol, 1990 ) Van der Merwe et al., ) Van der Merwe et al., 2001 ) Hutchings et al., 1996 Roberts, 1990 Roberts, 1990 ) ) ) Gerstner, 1939 Watt and Breyer-Brandwijk, 1962 Luseba and Van der Merwe, 2006 heartwater, redwater, internal parasites, Anthelmintics for calves ( Breyer-Brandwijk, 1962 goats and sheep ( Used by Zulus for colic in( cattle et al., 2001 Administered to horses as prophylactics against horse sickness ( Breyer-Brandwijk, 1962 ( aerial parts used as poultice forlumpy wounds, skin disease and as tick( repellent Cocks, 2001 2001 2001 2001 aid expulsion of afterbirth in animalshumans and ( general ailments, abortion ( Merwe et al., 2001 Unspecified parts are used as purgatives for calves ( Sotho and Swazi use topical leaf decoctions to prevent parasites developing in animal wounds ( Breyer-Brandwijk, 1962 leaf infusions and bark scrapings as anthelmintics for dogs, calves and donkeys ( human eye complaints ( Breyer-Brandwijk, 1962 discharge ( (Schweinf.) (Szyszyl.) J. V. L. Used by Zulus as a drench for sick horses (Lam.) Wild & (L.f.) Wild & Drum. Cattle diseases ( L.f. Gallsickness in stock ( (L.f.) Gilg & Brandt Cattle diseases ( L. Retained placenta ( L. Retained placenta, bloat ( (Kunze) Baill. Internal parasites in livestock ( Solms Retained placenta, bloat, vaginal Thunb. Pastes or infusions used for animal and (Rohrb.) N.E. Br. Decoctions taken or applied externally to Sond. ex Schauer Eye infections ( Rhoicissus tridentata Rhoicissus digitata Rhoicissus tomentosa Drum. Tribulus terrestris Cyphostemma natalitium D. Merwe Siphonochilus aethiopicus B.L. Burtt Cissus quadrangularis Grewia occidentalis Triumfetta sonderi Typha capensis Stangeria eriopus Lantana rugosa Vitex zeyheri Pouzolzia mixta Clerodendrum glabrum ) Continued Vitaceae Vitaceae Vitaceae Zygophyllaceae Vitaceae Zingiberaceae Vitaceae FamilyTiliaceae Species Indication Plant part used Chemical constituents Screened for activity Tiliaceae Typhaceae Table 1 ( Zamiaceae Verbenaceae Verbenaceae Urticaceae Verbenaceae

14 L.J. McGaw, J.N. Eloff / Journal of Ethnopharmacology xxx (2008) xxx–xxx

Many diseases affect livestock and other animals, and causal Gunnera perpensa (Gunneraceae) is a widely used herb for organisms of disease include protozoa, viruses, bacteria, fungi endometritis and retained placenta in cattle, and extracts of the and helminth parasites. Ticks are important vectors of several rhizomes were investigated for antibacterial efficacy (McGaw et economically important ailments such as heartwater, anaplasmo- al., 2005). The relatively weak antibacterial activity of Gunnera per- sis, sweating sickness and babesiosis, and several plant remedies pensa extracts against four bacterial species did not appear to be a are used to rid animals of ticks. Ethnoveterinary medicine may major factor in the reputed activity of the plant, but its known utero- play a significant role in the management of such diseases in a tonic activity was probably largely responsible (Kaido et al., 1997). cost-effective and accessible manner, and there are an increasing In a screening procedure of 17 plant species used to treat number of publications in the scientific literature reporting on the infectious diseases in cattle, McGaw et al. (2007) used the bac- ethnopharmacological activity of plants used in traditional veteri- teria recommended for antibacterial testing by the NCCLS (1990), nary medicine. It is essential to evaluate not only the bioactivity namely Escherichia coli, Enterococcus faecalis, Pseudomonas aerug- but also the safety of such plant treatments if their use is to be inosa and Staphylococcus aureus. Hexane, methanol and water promoted and potentially developed for commercial purposes. It is extracts were generally more active against the Gram-positive bac- expensive and ethically complex to conduct in vivo experiments, teria, confirming earlier reports of increased susceptibility of these and large quantities of test material and specialized facilities are organisms (Vlietinck et al., 1995). McGaw et al. (2007) reported required; hence many studies involve in vitro investigations of a that a third of the plant extracts screened exhibited MIC values less particular bioactivity. than 1 mg/ml, rationalising to an extent the use of these plants in The methods of preparation as well as application and dosages EVM. The same plant extracts were also screened for anthelmintic are critical factors to account for when evaluating a tradi- activity using as test organism the free-living nematode Caenorhab- tional remedy, but for the sake of consistency, many researchers ditis elegans (McGaw et al., 2007), and more than a third of extracts employ standard laboratory extraction techniques using a vari- exhibited activity. In the brine shrimp assay to evaluate cytotoxicity, ety of solvents to extract potential active compounds from plant some degree of toxic effect to the brine shrimp larvae was shown material. The type of assay and appropriate selection of test organ- by 30% of extracts but the lowest LC50 value was a relatively high ism(s) are also important in verifying a particular activity. The 0.6 mg/ml (McGaw et al., 2007). concept of immune support rather than direct destruction of Following the preliminary screening study showing high levels microorganisms may be a significant mechanism of action for of antibacterial efficacy in extracts of Ziziphus mucronata (Rham- EVM remedies. These features and others complicate the issues naceae) (McGaw et al., 2007), further work was conducted on this associated with evaluating and assessing the rationale for EVM plant. Compounds were isolated from leaves of the plant: 2,3- treatments. dihydroxyl-up-20-en-28-oic acid and zizyberanalic acid (Moloto, Several research articles focus on the potential antibacterial 2004). The first compound demonstrated excellent activity against activity of ethnoveterinary plants, often on the basis that bacterial Staphylococcus aureus, promoting claims of the efficacy of a Ziziphus diseases such as wound infections are likely to be more easily diag- mucronata leaf paste in treating bacterial infections in animals and nosed by rural livestock owners than a viral infection for example. humans. Luseba and co-workers (2007) tested dichloromethane extracts for Antifungal activity studies of extracts of Terminalia species antibacterial and anti-inflammatory activity in a study appraising (Combretaceae) against clinical isolates of the most common and the efficacy of South African medicinal plants used in the treatment important disease-causing fungi in animals have also revealed of wounds and retained placenta in livestock. Cissus quadrangularis interesting results (Masoko et al., 2005). The test fungal pathogens stem and Jatropha zeyheri root extracts were selectively inhibitory represented the various morphological fungal forms, namely in the anti-inflammatory assay against cyclooxygenase-2 enzyme. yeasts (Candida albicans and Cryptococcus neoformans), moulds The extracts tested were not mutagenic in the Ames test against (Aspergillus fumigatus) and thermally dimorphic fungi (Sporothrix Salmonella typhimurium strain TA98. In an interesting discussion, schenckii). Acetone extracts, out of hexane, dichloromethane, ace- Luseba et al. (2007) claimed that although water is traditionally tone and methanol extracts of Terminalia leaves, displayed the a commonly available solvent to prepare medicinal extracts, the highest antifungal activity. activity of organic extracts need not be disregarded. In livestock Anti-babesial and anti-rickettsial in vitro assay systems have also wound treatment, the whole plant is often processed and applied been used to test EVM plant extracts. Naidoo et al. (2005) used a cell locally, and with disorders such as retained placenta where the culture-based anti-babesial test, exposing Babesia caballi cultures treatment mixtures are given orally (probably unfiltered), active to plant extracts, and demonstrating activity at 100 ␮g/ml in the ingredients may be made available (Luseba et al., 2007). acetone extract of Elephantorrhiza elephantina rhizome. This species Bizimenyera et al. (2005) used a serial microplate dilution is a popular ethnoveterinary plant. Urginea sanguinea, Rhoicissus tri- technique (Eloff, 1998) to identify antibacterial activity against dentata and Aloe marlothii acetone extracts were not active against Staphylococcus aureus (Gram-positive) and Pseudomonas aerugi- the babesia cultures using this assay (Naidoo et al., 2005). The nosa (Gram-negative) in organic solvent extracts of Peltophorum anti-babesial drugs used as controls, imidocarb and diminazene, africanum (Fabaceae). Antioxidant activity was also determined exhibited EC50 values of 0.08 and 0.3 ␮g/ml, respectively. Naidoo et (Bizimenyera et al., 2005). Pastoralists use extracts of the root and al. (2006) evaluated the anti-rickettsial activity of Elephantorrhiza bark to treat stomach ailments such as diarrhoea and dysentery elephantina and Aloe marlothii in an in vitro Ehrlichia ruminantium in cattle (Bizimenyera et al., 2005), and the detected antibacte- culture system. Ehrlichia ruminantium cultures were incubated with rial activity, as well as antioxidant efficacy, provides some support acetone extracts of the leaves and results were compared to those to the traditional EVM use against bacterial infections. Masika obtained with oxytetracycline and untreated controls. Elephantor- and Afolayan (2002) tested extracts of three plant species used rhiza elephantina and Aloe marlothii both possessed anti-ehrlichial for livestock disease treatment, namely Combretum caffrum, Salix activity with EC50 values of 111.4 and 64.5 ␮g/ml and EC90 values capensis and Schotia latifolia, for antibacterial and antifungal activ- of 228.9 and 129.9 ␮g/ml, respectively. The EC50 and EC90 values ity. They reported some activity against Gram-positive bacteria for oxytetracycline were 0.29 and 0.08 ␮g/ml. It was proposed that (with MIC values as low as 0.1 mg/ml). Most extracts were not the plant extracts may be inhibitory against the Ehrlichia parasite active against Gram-negative bacteria but generally all of them by a similar mechanism to each other, which was unrelated to the were active against the five test fungi (Masika and Afolayan, 2002). mechanism of action of the tetracyclines (Naidoo et al., 2006).

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In further work on the popular ethnoveterinary plant, Peltopho- possible should be confirmed with in vivo tests. Alternatively, rum africanum, which is used in treating helminth diseases, the if facilities for in vivo studies are not available, a battery of in acetone extracts of the leaf, bark and root were screened for activ- vitro assays designed to investigate potential modes of action will ity against Haemonchus contortus and Trichostrongylus colubriformis also provide useful information. Investigation of synergistic effects in the egg hatch and larval development assays (Bizimenyera et where plants are used in combinations would also be useful. al., 2006a,b). At relatively low concentrations of 0.2 mg/ml, the The development of active plant extracts with reliable bioactiv- extracts showed activity, which supports the use of the plant for ity and little or no toxicity is a practical pursuit with commercial anthelmintic purposes. potential. Additionally, lead structures with novel or more effec- A promising area of research involves the investigation of tive mechanisms of action are required to overcome the problems anti-tick activity of plant extracts, entailing observation of tick of drug resistance encountered in several disease-causing organ- repellent and toxic effects of plants. Allium species were investi- isms. gated for repellency and toxicity against Hyalomma marginatum Motivation for the study of South African ethnoveterinary plants rufipes adults (Nchu, 2004). The acetone extract of Allium porrum largely resides in validating the efficacy of remedies used by rural revealed a high repellency index (65–79.48%), and Allium sativum stock owners. An essential component of this evaluation of plants dichloromethane extract was toxic to 100% of ticks within an hour should involve toxicity studies, to enable cautions to be issued of of exposure. Essential oils from the aerial parts of Lippia javanica and dangerous practices or toxic effects of plants. Further research is Tagetes minuta were repellent toward the ticks in a concentration required to highlight bioactivity not due to non-specific toxic effects dependent manner (Nchu, 2004). In a growth inhibition bioassay, on microorganisms and mammalian cells. In this paper, more than it was shown that Tagetes minuta essential oil delayed molting to 200 plant species were recorded in the available literature as being adult stage of 60% of engorged nymphs of Hyalomma marginatum employed in EVM, and of these, a mere 27 species have been tested rufipes (Nchu, 2004). for bioactivity in targeted ethnoveterinary assays. More plants need Zorloni (2007) investigated 28 Ethiopian plants used for eth- to be evaluated, and more investigation of those plants already noveterinary tick control purposes for repellent and toxic effects tested in one or two screening systems needs to be carried out. against adult Rhipicephalus pulchellus ticks. Promising repellency The unique heritage of South Africa, both in terms of its rich plant was exhibited by organic solvent extracts of many species, with diversity and its cultural traditions of utilizing that plant wealth, Calpurnia aurea revealing the best tick toxicity (Zorloni, 2007). Ethyl needs to be studied and developed for the benefit of all its people acetate extracts of Senna italica subsp. arachoides demonstrated and animals. a concentration dependent acaricidal activity against Hyalomma marginatum rufipes (Thembo, 2006). Results of an in vivo exper- Acknowledgements iment suggested that aqueous extracts of Senna italica subsp. arachoides given to guinea pigs and rabbits may hinder the feeding The National Research Foundation (NRF) and the University of performance of adult Hyalomma marginatum rufipes ticks (Thembo, Pretoria are thanked for financial support. 2006). Other plants used traditionally as arthropocides in South Africa, namely Eucalyptus globoidea and Lavendula angustifolia, were References reported by Mkolo (2008) to be effective tick repellents. These studies demonstrate that South African plants have Bizimenyera, E.S., Swan, G.E., Chikoto, H., Eloff, J.N., 2005. Rationale for using Pel- good potential for the discovery of biologically active extracts tophorum africanum (Fabaceae) extracts in veterinary medicine. Journal of the South African Veterinary Association 76, 54–58. and isolated compounds with interesting effects against a range Bizimenyera, E.S., Githiori, J.B., Swan, G.E., Eloff, J.N., 2006a. In vitro ovicidal and of disease-causing organisms, or disease-transmitting ticks. Only larvicidal activity of the leaf, bark and root extracts of Peltophorum africanum around 13% of EVM plants in South Africa have been evaluated for Sond. (Fabaceae) on Haemonchus contortus. Journal of Animal and Veterinary some sort of biological activity in ethnoveterinary studies. Much Advances 5, 608–614. Bizimenyera, E.S., Githiori, J.B., Eloff, J.N., Swan, G.E., 2006b. In vitro activity of Pel- work needs to be done to evaluate more types of bioactivity as well tophorum africanum Sond. (Fabaceae) extracts on the egg hatching and larval as other plant species, particularly those that are widely used and development of the parasitic nematode Trichostrongylus colubriformis. Veteri- readily available. 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