South African traditional medicinal plant trade—Challenges in regulating quality, safety and efficacy

South African traditional medicinal plant trade—Challenges in regulating quality, safety and efficacy

Journal of Ethnopharmacology 119 (2008) 705–710 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevie...

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Journal of Ethnopharmacology 119 (2008) 705–710

Contents lists available at ScienceDirect

Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm

South African traditional medicinal plant trade—Challenges in regulating quality, safety and efficacy R.A. Street, W.A. Stirk, J. Van Staden ∗ Research Centre for Plant Growth and Development, School of Biological and Conservation Sciences, University of KwaZulu-Natal Pietermaritzburg, Private Bag X01, Scottsville 3209, South Africa

a r t i c l e

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Article history: Received 9 May 2008 Received in revised form 18 June 2008 Accepted 19 June 2008 Available online 27 June 2008 Keywords: Drug development Environmental contaminants Medicinal plants Pesticide residue Toxic metal accumulation

a b s t r a c t Based on the long history of medicinal plant use, users of traditional medicines accept that they are safe for human consumption. However, the absence of regulation of the medicinal plant trade in aspects such as collection, processing and storage provides no such guarantee. Environmental pollution, misidentification and adulteration provides further grounds for concern. The potential adverse effects of South African traditional medicines are not well documented. There are only a few investigations of mutagenic properties and heavy metal contamination. In the absence of regulatory controls, the safety and quality of medicinal plants vary considerably. The current comprehension and future challenges regarding quality, safety and efficacy of South African traditional medicine are discussed. © 2008 Elsevier Ireland Ltd. All rights reserved.

1. Introduction It is estimated that around 27 million South Africans depend on traditional medicine for their primary health care needs (Mander, 1998). The reliance of such a large portion of the population on traditional medicine can be attributed to a number of factors; relatively good accessibility to the plants, affordability and extensive local knowledge and expertise amongst the local communities (Mander et al., 1996). Secondary metabolites obtained from plants are not benign molecules (Gurib-Fakim, 2006). Plants have evolved such chemical defenses in order to deter, stun, poison or kill threatening species. It would therefore be naive to assume that plant extracts are inevitably safe (Gurib-Fakim, 2006). Nonetheless, a common misconception is that medicinal plants are “pure and natural” which equates to “harmless”. Inappropriate methods of collection, processing and storage with undesirable contaminants in the products, have all contributed to the negative impact with regards to African natural plant products competing in international markets (Tadmor et al., 2002). The regulation of traditional medicinal plant use embodies three fundamental aspects: quality, safety and efficacy. Unfortunately, comprehensive safety and efficacy data on traditional medicines

∗ Corresponding author. Tel.: +27 33 2605130; fax: +27 33 2605897. E-mail address: [email protected] (J. Van Staden). 0378-8741/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2008.06.019

are lacking (Springfield et al., 2005). The shortage of safety and quality controls of South African medicinal plants is further compromised by the fact that there is currently no pharmacopoeia that documents indigenous medicinal plants of South Africa (Fennell et al., 2004a). The objective of this paper is to discuss factors which influence the safety, quality and efficacy of medicinal plants and to highlight current knowledge and future challenges of the South African medicinal plant trade. 2. Factors compromising quality, safety and efficacy of South African medicinal plants Many South African medicinal plants are harvested from the wild. This not only threatens medicinal plant biodiversity and population stability but also leads to speculation with regard to safety as industrial encroachment has led to contamination of water sources and natural habitats. The deposition of processed and unprocessed mining and industrial waste materials (Naicker et al., 2003; Roychoudhury and Starke, 2006) have led to questions of safety for South African medicinal plants that are harvested near to these resources. According to Verster et al. (1992) large quantities of polluted water and tonnes of dry sewage sludge is being disposed on South African soils—much of this on agricultural land. Numerous reports have revealed heavy metal contamination of South African rivers and soils (Abbu et al., 2000; Binning and Baird, 2001; Okonkwo and Mothiba, 2005). As a result of polluted harvest sites or poor farming practices, medicinal plant products may

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be contaminated with pesticides, microbial contaminants, heavy metals, toxic substances and adulterants (Chan, 2003). Due to genetic, ecological and environmental differences, plants harvested from the wild generally vary in quality and consistency of active compounds (Bopana and Saxena, 2007). Medicinal plant gatherers collect their materials throughout the year to supply the persistent demand for medicinal plants. If mature trees or plants cannot be found, then younger ones suffice, which results in availability of inconsistent plant material of the same species (Von Ahlefeldt et al., 2003). Plant age, seasonal variation and geographical deviation in harvest site are contributing factors towards variation in biological activity (Taylor and Van Staden, 2001; Shale et al., 2005; Buwa and Van Staden, 2007). Collections of Harpephyllum caffrum Bernh. (Anacardiaceae) bark from the same female tree at different times of the year showed the highest antibacterial activity in summer months (Buwa and Van Staden, 2007). A study by Taylor and Van Staden (2001) on the effect of age, season and growth conditions on the anti-inflammatory activity of Eucomis autumnalis (Mill.) Chitt. (Hyacinthaceae) plant extracts showed significant differences between plants harvested before and after the growing season with the highest anti-inflammatory activity (COX1 inhibition) shown shortly before the onset of dormancy. The age of plant affected COX-1 inhibition, with young plants having large amounts of COX-1 inhibitory activity, particularly in leaves. However, as the plants matured, more activity was associated with the underground plant parts (bulb and root). Thus, harvesting plants from undisclosed harvest sites throughout the year may result in inconsistent quality of available plant material. Proper drying conditions are largely overlooked by the collectors, growers and traders (Ramakrishnappa, 2002). Inadequate drying may result in mould growth (Whitten, 1997), which can lead to deterioration of the plant product (Ramakrishnappa, 2002). Yeasts and moulds can cause opportunistic infections in humans and are more significant in HIV patients (Govender et al., 2006). A recent study on South African medicinal plants recommended for the treatments of HIV/AIDS revealed that many plants had high bacterial and fungal numbers due to low environmental sanitation and a low standard of processing during preparation (Govender et al., 2006). A study on African herbal teas showed samples containing a high microbial count, unacceptable in modern food and food supplement markets (Tadmor et al., 2002). The effect of harvest and duration of storage on quality and efficacy remains understudied (Fennell et al., 2004a). The effect of storage on biological activity was carried out on nine frequently used medicinal plants of South Africa (Stafford et al., 2005). On the whole, antibacterial activity was retained while anti-inflammatory activity (COX-1 inhibition) was lost. Changes in the chemical composition of the plant material during storage were shown through the use of TLC-fingerprints. According to Stafford et al. (2005), phytochemical stability is species-specific and no general assumption can be made with respect to recommended shelf-life. Whether in the fresh, desiccated or semi-processed state, the accurate identification of medicinal plant species is fundamental with respect to quality control (Springfield et al., 2005). The wellbeing of the consumer is compromised due to poorly trained plant vendors who misidentify plant materials (Grace et al., 2002; Fennell et al., 2004b). Medicinal plants collected from the wild may be contaminated by other species or plant parts through misidentification (WHO, 2003). Poisoning from traditional medicines is frequently a consequence of misidentification (Stewart et al., 1998). Jatropha curcas L. (Euphorbiaceae), a medicinal plant commonly associated with poisonings in South Africa (Munday, 1988), was the cause of 11% (50) of the total number of acute poisonings (442) admitted to Ga-Rankuwa Hospital due to accidental ingestion of the seeds—all cases were children (Mampane et al., 1987).

The bulk of the medicinal plant trade takes place at informal street markets and involves the sale of unprocessed or semiprocessed products. Raw plant material undergoes very little processing (e.g. grinding or boiling) before being administered to the patient (Mander and Le Breton, 2006). The deliberate addition of biologically active material to a plant preparation (known as adulteration) is a common method of malpractice used to enhance the efficacy of the products (Yee et al., 2005). There had been no reports of deliberate adulteration of traditional African herbal remedies until recently with reports of two separate incidences in which South African traditional remedies were adulterated with western pharmaceuticals causing severe toxicity (Snyman et al., 2005). In the preparation of traditional medicinal plants, efficacious compounds are not extracted individually from the plants. Instead the whole plant, parts thereof or crude extracts (extracted with the use of alcohol or water), are used (Drewes et al., 2006). Many traditional health practitioners believe that isolated compounds have weaker efficacy than whole plant extracts (Rodriguez-Fragoso et al., 2008). Owing to the fact that traditional medicines are complex mixtures of more than one active ingredient, possibilities of interaction between herbal and conventional drugs are increased (Ernst, 2000). Unfortunately, herbal–drug interactions and the consequences thereof is a poorly studied field. If neglected, it may have serious negative implications on today’s ‘herbal boom’ (Ernst, 2000). For example, two South African medicinal plants often recommended for the treatment of HIV/AIDS include Hypoxis hemerocallidea Fisch. & C.A. Mey. (Hypoxidaceae) and Sutherlandia sp. (Fabaceae). However, despite the support of the Ministry of Health and NGOs, no clinical trials of efficacy exist (Mills et al., 2005a). Alarmingly, the plants have shown a negative interaction with antiretroviral medication (Mills et al., 2005b). Thus patients may be at risk from treatment failure, viral resistance or drug toxicity (Mills et al., 2005b). Although it is customary for traditional healers to make inquiries regarding the prescription drugs used by their patients, the lack of scientific evidence with regards to herbal–drug interactions does not equip the healers to make informed decisions (Mirranda Javu, South African traditional health practitioner, personal communication). Throughout southern Africa, plant material that is dried (roots or bark), or has an extensive shelf-life (bulbs, seeds and fruits) dominates traditional medicinal markets (Fig. 1) (Cunningham, 1993). South African medicinal plants are most commonly sold at informal street markets or indoor shops. The outdoor markets are customarily positioned in the hub of the city center to allow easy access for commuters. A rudimentary cover may keep direct sunlight or rain off the trader but most of the plants are displayed in the open (Fig. 1). Therefore, plant material may come in contact with

Fig. 1. Informal street market, Pietermaritzburg, South Africa.

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various kinds of urban pollution such as industrial and vehicular emissions. Furthermore, the plant material is exposed to microbial and insect attack (Stafford et al., 2005). Pests are a frequent problem for medicinal plant vendors and fumigation does take place in medicinal plant shops. Shop owners, however, do not seem to be concerned about the consequences of potentially toxic residues on the plant material being sold to their patients (Fennell et al., 2004a). Pesticide and herbicide residues are a common contaminant of medicinal plants (Dogheim et al., 2004; Rodrigues et al., 2006). Captan, a commercial pesticide with known mutagenic, genotoxic and teratogenic activity, was recently isolated from Cyrtanthus suaveolens Schönland (Amaryllidaceae), a medicinal plant widely used in southern Africa (Elgorashi et al., 2004). The packaging used for plant products includes newspaper and plastic packets. A survey of rural clinic patients (n = 100) in South Africa revealed that 84% would prefer more hygienically packaged indigenous medicine. Most consumers indicated that they would also prefer more modernized and hygienic trading venues (Mander, 1998). The lack of storage facilities and trading infrastructure results in the spoiling of plant material. Thus, undesirable wastage and/or a decrease in product quality is common (Mander, 1998). Poisonings by traditional plant-based remedies in South Africa is not uncommon, particularly in children (Stewart et al., 1999; Steenkamp et al., 2002). Nonetheless, medicinal personal tend not to ask about the use of traditional medicines administered to young children, especially not babies (Van Wyk and Els, 2008). A recent case study reported a single case of neonatal organo-phosphatelike poisoning, presumed to be caused by traditional medicine. The traditional healer was contacted and a sample of the traditional medicine administered to the child was sent for analysis. Unfortunately, the specimen was misplaced during transfer and no analysis could be performed (Van Wyk and Els, 2008). An analysis of the Johannesburg forensic database over a 5-year period (1991–1995) revealed 206 cases in which a traditional remedy was either stated to be the cause of death or was found to be present in a case of poisoning with an unknown substance (Stewart et al., 1999). Heavy metals were accountable for 10% of these poisonings. Heavy metals are a known contaminant or adulterant of many traditional remedies (Ernst, 2004; Haider et al., 2004; Obi et al., 2006). Senecio coronatus (Thunb.) Harv. (Asteraceae) is known to hyperaccumulate nickel (Przybylowicz et al., 1995) and is an extensively used medicinal plant in South Africa (Dold and Cocks, 2002). Human overexposure to nickel has the potential to produce a variety of pathologic effects including skin allergies, lung fibrosis and cancer of the respiratory tract (Kasprzak et al., 2003). Toxicity reports show that root decoctions of Senecio coronatus, administered by enema, caused the fatal veno-occulusive disease in infants (Savage and Hutchings, 1987). Similarly other metal accumulating medicinal plants such as Datura metal L. (Solanaceae), an accumulator of cobalt and nickel (Bhattacharjee et al., 2004) and Datura innoxia Miller, Gard. a metal tolerant species (Kelly et al., 2002), are used in South African medicine. Both species have been reported as toxic (Hutchings et al., 1996). It is known that a number of traditional remedies give rise to severe renal pathology, the mechanism of which is uncertain but which could be associated with heavy metal toxicity (Steenkamp et al., 2002). The metals most commonly implicated in morbidity and death in South Africa are arsenic, chromium and magnesium (Steenkamp et al., 2002). Nevertheless, few comprehensive studies have been done to assess the heavy metal content in South African medicinal plants. Steenkamp et al. (2000) determined heavy metal concentrations in plants and urine from patients treated with traditional remedies. Although few plants had high levels of toxic metals, the concentrations in those that did were sufficiently high to cause concern. Another screening of South African medicinal plants for

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heavy metal contamination revealed that plant samples, obtained from informal street markets, contained arsenic and cadmium at levels exceeding the WHO limits of 1.0 and 0.3 mg/kg, respectively (WHO, 1998), and lead and nickel were detected in all samples (Street et al., 2008). A number of South African medicinal plant species, from a range of plant families, have revealed cytotoxic and genotoxic effects (Taylor et al., 2003; Steenkamp et al., 2005; Steenkamp and Gouws, 2006; Luseba et al., 2007; McGaw et al., 2007). With some contradictory findings regarding toxicity of certain plant species, differences in results may be attributed to differences in extraction methods and the natural variability in plants. Different cell lines demonstrate different sensitivities towards the plant extracts (Steenkamp and Gouws, 2006). The mutagenic and antimutagenic properties of South African medicinal plants are covered in a review in this issue. Despite the range of medicinal plants used and the rich biodiversity of South Africa, only a relatively small number of plant species have been scientifically validated (Springfield et al., 2005). In many developing countries, due to their long history of use, it is deemed adequate to merely demonstrate biological activity of plant remedies (Jäger and Van Staden, 2005). A large portion of South African medicinal plants tested for biological activity are obtained from informal medicinal markets, which may contain elevated levels of contamination (Street et al., 2008). As environmental contaminants such as heavy metals can affect biological activity (Murch et al., 2003; Narula et al., 2005; Rai et al., 2005), researchers should be aware of the effect of environmental contaminants when reporting on biological activity of crude plant extracts. 3. Future challenges Health, safety and quality assurance are universal concerns with regards to the regulatory requirements and standards of traditional medicine (Diederichs et al., 2006). The correct documentation and traceability of medicinal plants that enter into regional and international trade need to be maintained and monitored. Investigations regarding the effect of cultivation, drying and storage practices on safety, quality and efficacy of South African medicinal plants will not only benefit the consumer but will also ensure sustainable use of the medicinal plants (Fennell et al., 2004a). Loss of biodiversity through over harvesting of medicinal plants may not only lead to diminishing biological resources, but also a loss of cultural practices (Wiersum et al., 2006). The potential loss of cultural value which has a strong link to medicinal plant biodiversity supports the initiative for conservation of medicinal plant biodiversity (Anyinam, 1995; Wiersum et al., 2006). Good agricultural practice (GAP) is the first step in quality assurance, upon which the safety and efficacy of plant-based medicinal products directly depend (WHO, 2003). Until now, only the European Union and a few other countries, such as China and Japan have developed regional and national guidelines for good agricultural and collection practices for medicinal plants (WHO, 2003). Such guidelines are regulated and monitored to ensure soil and irrigation water are within the limits or free from harmful heavy metals, pesticides, herbicides and toxicologically hazardous substances. Although many studies have recommended the cultivation of South African medicinal plants (Sparg et al., 2005; Crouch et al., 2006), there is little information on the response of these medicinal plants to agricultural practices such as frequent watering and fertilization regimes. According to the World Health Organization (WHO) guidelines on good agricultural and collection practices (GACP) (WHO, 2003), soil should contain sufficient amounts of essential elements and organic matter to ensure optimal medicinal plant growth and quality. The Water Research Commission of South

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Africa has issued a set of maximum permissible heavy metal levels in agricultural soils (WRC, 1997). However, as implied by Street et al. (2007), the permissible levels may be too high for normal plant growth and development of wild medicinal plants. Thus, separate threshold limits for metal elements need to be established for the cultivation of traditional medicinal plants. Despite the fact that certain more conventional traditional healers believe that plants grown as agricultural crops will not have the same medicinal properties as those harvested from the wild (Cunningham, 1993), 82% of urban-based healers (n = 57) and 69% of the clinic patients (n = 138) in the Eastern Cape reported that they would make use of cultivated plants for medicinal purposes (Dold and Cocks, 2002). Evaluating and monitoring potentially harmful substances is an essential step in improving the overall safety and quality of widely used medicinal plants which will in turn result in safeguarding the consumer. Assessing heavy metal and microbial contamination of medicinal plants has become an integral part of Good Agricultural Practice (WHO, 1998). As certain South African medicinal plants are known to accumulate heavy metals (Przybylowicz et al., 1995; Bhattacharjee et al., 2004), research into potential accumulator species, which will enter into the food chain, need to be thoroughly investigated and reported. Many medicinal plants are susceptible to climatic conditions, requiring proper drying and storage under precise temperature and humidity (Ramakrishnappa, 2002). Food preservation techniques, frequently used to stop degradation of agricultural products, should be adopted for the medicinal plant trade (Fennell et al., 2004a). Such techniques are imperative as there may be a long time period between harvesting and point of sale (Grace et al., 2002). Implementation of correct post-harvest techniques will allow the timely disposal of medicinal plants with unstable compounds and will therefore contribute to the quality and efficacy of these plants. Challenges in biological screening remain a key focus in drug discovery from medicinal plants (Balunas and Kinghorn, 2005). “Too many papers are published which extrapolate results from in vitro tests to claim in vivo activity and efficacy without taking into account biopharmaceutical factors, traditional methods of making actives, treatment of the extract prior to administration, the effect of other added substances or the dose showing activity” (Houghton et al., 2007). There are numerous reports of noteworthy pharmacological properties of plant extracts without identification and a vast number of isolated compounds remain devoid of comprehensive biological and clinical assessment (Graz et al., 2007). Many plants show promising biological activity in assays which later fail to have the activity confirmed on subsequent re-collections. This may be due to the chemistry of the plant or the bioassay system used or mix-ups in labeling of plant samples or incorrect taxonomic identification (Fabricant and Farnsworth, 2001). The chemistry of relatively few South African medicinal plants has been studied in detail (Drewes et al., 2006). Perhaps the biggest obstacle to natural plant chemistry is the continual supply of large amounts of natural plant product required for further evaluation. Plant-based compounds are typically isolated in small quantities that are insufficient for drug discovery, drug development and clinical trials (Balunas and Kinghorn, 2005). Owing to the fact that millions of South Africans rely on traditional medicines for their primary health care needs, there is insufficient pragmatic information regarding the pharmacology and toxicology of commonly used herbal remedies. This information should be available to health care workers such as doctors, pharmacists, nurses, and social workers (Rodriguez-Fragoso et al., 2008). As the current research is aimed at investigating medicinal plants for commercially useful compounds, it does not directly benefit the majority of the users, including traditional healers,

gatherers and traders (Light et al., 2005). A major downfall of ethnobotanical research in South Africa is the inadequate transfer of knowledge back to local communities (Fennell et al., 2004a). Although some researchers are not conscious of the importance of relaying their findings to the public (Jäger, 2005), the majority are ill-equipped to undertake such an important yet largely overlooked step. There needs to be a shift in ideology and practice whereby healers, sociologists, scientists and medicinal practitioners work together to bridge the gap between the healing remedies, laboratories and hospitals. Scientific findings need to filter through to consumers, and just as importantly, consumer reports on adverse reactions should be accepted as a serious source of information, placing emphasis on current and relative problems. 4. Conclusions Unfortunately, South Africa is being left behind on all fronts because of its lack of direction and focus when it comes to the outcome of various challenges in the South African medicinal plant trade. The number of South African medicinal plants screened for the validation of biological activity far outweighs the assessment for potentially toxic compounds and contaminants. Once off studies on biological activity and/or toxicity of South African medicinal plants by and large do not develop into more comprehensive investigations. In many cases, simply reporting on biological activity is deemed sufficient (Jäger and Van Staden, 2005). Unfortunately, the shortage of researchers and equipment to carry out phytochemical analysis is a major stumbling block (Mulholland, 2005). Nonetheless, screening for efficacy, toxicity and stability of compounds should be incorporated into comprehensive programmes to provide a complete understanding of the effect of these plants (Fennell et al., 2004b). At grassroots level, the South African medicinal plant trade is a thriving industry, supplying primary health care to millions of South Africans, with or without guidance or advice from the scientific community. To date, most of the work focuses on screening and isolating potentially valuable compounds (Fennell et al., 2004a). Unfortunately, little is done to preserve or enhance the benefits that the existing trade already delivers to millions of consumers (Fennell et al., 2004a) namely to provide a product of quality and safety. Acknowledgements The National Research Foundation, South Africa, and the University of KwaZulu-Natal are thanked for financial support. References Abbu, R., Pillay, A.E., Moodley, K.G., 2000. The use of ICP-AES and anodic stripping voltammetry (ASV) to determine the levels of cadmium and lead in river water samples from KwaZulu-Natal (KZN), South Africa. Journal of Trace and Microprobe Techniques 18, 83–97. Anyinam, C., 1995. Ecology and ethnomedicine: exploring links between current environmental crisis and indigenous medical practices. Social Science and Medicine 40, 321–329. Balunas, M.J., Kinghorn, A.D., 2005. Drug discovery from medicinal plants. Life Sciences 78, 431–441. Bhattacharjee, S., Kar, S., Chakravarty, S., 2004. Mineral compositions of Datura: a traditional tropical medicinal plant. Communications in Soil Science and Plant Analysis 35, 937–946. Binning, K., Baird, D., 2001. Survey of heavy metals in the sediments of the Swartkops River Estuary, Port Elizabeth, South Africa. Water SA 27, 461–466. Bopana, N., Saxena, S., 2007. Asparagus racemosus—ethnopharmacological evaluation and conservation needs. Journal of Ethnopharmacology 110, 1–15. Buwa, L.V., Van Staden, J., 2007. Effects of collection time on the antimicrobial activities of Harpephyllum caffrum bark. South African Journal of Botany 73, 242–247. Chan, K., 2003. Some aspects of toxic contaminants in herbal medicines. Chemosphere 52, 1361–1371.

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