**1. Introduction**

166 Toxicity and Drug Testing

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Flockhart & G. G. Illei (2004). Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis. Traditional medicines occupy a central place among rural communities of developing countries for the provision of health care in the absence of an efficient public health care system (WHO, 2003).

The use of traditional remedies is common in sub-Saharan Africa, and visits to traditional healers remain a mainstay of care for many people because of preference, affordability, and limited access to hospitals and modern health practitioners (Homsy et al., 1999).

It is an important part of medical care in Uganda and throughout Africa, representing first line therapy for 70% of the population, (Homsy et al., 2004). For many, traditional herbal medicines may be the only source of treatment available. The main reasons to explain this are: traditional medicines are often more accessible compared with licensed drugs; there are no records attesting the resistance to whole-plant extracts possibly due to the synergistic action of their constituents; phytotherapy, possibly produces fewer adverse effect than chemotherapy (Willcox and Bodeker, 2000).

In Africa more than 2,000 plants have been identified and use as herbal medicines. However, very few of these plants have been screened for safety in resource-constrained countries including Uganda. It is time to ask in a systematic and scientific manner how these local treatments work, what are the best means to establish their safety and can they be used as traditionally prepared? The source of antimalarial drugs such as artemisinin derivatives and quinolines currently in use today were isolated from medicinal plants. Renewed interest in traditional pharmacopoeias has meant that researchers are concerned not only with determining the scientific rationale for plants usage, but also with the discovering of novel compounds of pharmaceutical value for the treatment of malaria.

Herbals are as old as human civilization and they have provided a complete storehouse of remedies to cure acute and chronic diseases. Numerous nutraceuticals are present in medicinal herbs as key components. Scientific evaluation of herbal products has been limited, yet herbal products are the most commonly consumed health care products. Because of known pharmacological effects and potential interaction of many of these compounds with therapeutic drugs, a history of herbal intake should be considered as part of routine medical history and should be evaluated before any change in prescription drugs and before medical procedures (Schwartz et al 2000)

Herbal Medicine in the Treatment of Malaria:

some other countries in the continent.

flavonoids.

**2. Methods** 

**2.1 Research design** 

obtained for this research study.

possessing significant pharmacological activity.

*Vernonia amygdalina*: An Overview of Evidence and Pharmacology 169

produces large mass of forage and is drought tolerant (Hutchioson and Dalziel, 1963), it is 2 – 5 m with petiolate leaf of about 6 mm diameter and elliptic shape. The leaves are green with a characteristic odour and a bitter taste. No seeds are produced and the tree has therefore to be distributed through cutting. It is known locally as Omubirizi in southwestern Uganda and used traditionally for pain relief and malaria attack. Patients are instructed to soak the plant leave in hot water about (80oC). They should then drink half a glass (about 0.25l) two times daily for 4-7 days. Smaller doses are prescribed for children according to their weight.They are used as vegetable and stimulate the digestive system in

 This plant has ethnomedical use in treating veneral diseases, gastrointestinal problems and malaria (Kambizi et al, 2001; Huffman et al, 2003; Hamill et al, 1992). Furthermore, they are used as local medicine against leech, which are transmitting bilharzias. Free living chimpanzees eat the leaves, if they have attacked by parasites (Huffman, M.A. 2003). There are reports concerning the hypoglycaemic, antineoplastic antibacterial and antioxidant properties of the plant. (Akah et al, 1992; Izevbigie et al, 2004; Taiwo et al, 1999; Iwalewa et al, 2005). Despite the varied uses of the plant, there are no information on its analgesic properties and exact toxicology on sub-chronic exposure, although some reports describe its antiplasmodial effects (Abosi et al 2005; Masaba et al 2000; Tona et al, 2004; Wilcox et al, 1999). Previous phytochemical reports have shown the presence of steroid, saponins,

Ninety traditional healers were identified through community and healers association leaders. Once identified, study staff members approached the individuals to determine eligibility. Eligibility criteria included 30 years of age and older, recognition as a traditional healer by the local community council, and having established an active practice in the community. Three districts (Kanungu/Bwindi area, Bushenyi and Mbarara) south-western Uganda were identified. With consent a taxonomist samples of antimalarial herb were

To evaluate consistency, interviews were conducted by a person specially trained in

The ethnographic interview included questions about common plant names, sources of products, method of preparation, purpose of use, quantity of herbs use and perceived benefit of herbs in ameliorating malaria symptoms and improving overall health. Ethical forms were used in order to assure them of the defense of their knowledge and intellectual property right was applied. Traditional healer's name, age, gender, and ethnicity tribe, were asked. We relied on the knowledge of healers and the taxonomist to select the products of greatest importance. This enabled us target products that have a high likelihood of

A strategy was developed that respected the healers' rights to maintain propriety of unique blends of herbal medicine. Also, a memorandum of understanding was developed that disclosed our study objective, which is to characterize the pharmacologic activity and to elucidate the toxicity of these remedies in order to determine any potential adverse effect. We emphasized that we were interested in general knowledge about the remedy and not in specific formulation, and that it was not our intention to use the knowledge gained from this

interview administration and who is fluent in the language of the participants.

At present, work conducted on traditional medicine in Africa has mainly concentrated on the collection, identification, and classification of herbal products for treatment of different ailments. However, research in the areas of safety and toxicology is lacking.

Traditional medicines, like modern pharmaceuticals can do harm, but because humans have been using herbal drugs for long time, they are considered safe and non-toxic so the toxicological actions of these agents have been mostly ignored, even while the effectiveness is either already known or under study (O'Hara et al., 1998). Willcox (1999), carried out a clinical study on 'AM' (coded to protect the intellectual property right of the traditional healers), a popular antimalarial herb that has a long history of use among the people of south-western Uganda. In her result, 'AM' significantly reduced parasite count between day 1 and day 7, patients showed symptomatic improvement, but 50% of them experienced some side effects including vomiting, nausea and stomach upset. These were partly attributed to malaria itself as well as to 'AM' ingestion (Willcox, 1999).

If the origin of herbs' toxicity is not identified, the adverse effects may be wrongly associated with other environmental exposures or some traditional belief. Failure to establish the true cause of exposure also means that the patient continues taking the toxic herb. Thus, the screening of traditional remedies for safety and toxicity is recommended to protect public health. On the other hand, several plants used in Uganda traditional medicine can cause damage to genetic material and therefore have potential to cause long-term damage in patients when administered as medicinal preparations (Steenkamp, 2005).

#### **1.1 The main groups of active principle or constituents obtained from medicinal herbs**

The therapeutic effects of plant species are determined by their constituents. These affect the condition and function of the various human body organs, clear up residual symptoms or destroy the cause of the disease in most cases infectious micro-organisms. They help increase the body's resistance to disease, retard or delay the processes of natural aging or facilitate the adaptation of the organism to certain conditions (Forantisek, 2001). Over the centuries, man used medicinal plants even though he was unable to find a rational explanation for their effects. It was not until the 19th century and after the rapid development of organic chemistry and pharmacology, that man determined which active or group of principles are responsible for a given therapeutic effect. Knowledge of these substances frequently served as a model for the synthetic preparation of new medicines, enabling the drug to be modified and made more effective. It was soon discovered that a better therapeutic effect was often obtained by the particular combination of active principle naturally present in each plant that by a single, isolated substance. The most important constituents are the secondary metabolism in plants, which includes alkaloids, glycosides, essential oils, tannins and the bitter principles. Products of secondary metabolism of plants are responsible for the plants' therapeutics effects. Of greater importance for the plants themselves of course are the products of primary metabolism which are necessary for the proper function of the basic life processes in plants. Primary metabolism products are also used by man. This group includes sugars, fatty oils, organic acids, vitamins and protein. These products of primary metabolism themselves may have no therapeutic effect but may possibly increase the efficiency of the therapeutically important principles (70)

#### **1.2** *Vernonia amygdalina*

(Aseraceae), also called bitter leaf is a popular African vegetable that grows as a shrub or small tree indigenous to Central and East Africa including Uganda (Huffman et al, 1996). It produces large mass of forage and is drought tolerant (Hutchioson and Dalziel, 1963), it is 2 – 5 m with petiolate leaf of about 6 mm diameter and elliptic shape. The leaves are green with a characteristic odour and a bitter taste. No seeds are produced and the tree has therefore to be distributed through cutting. It is known locally as Omubirizi in southwestern Uganda and used traditionally for pain relief and malaria attack. Patients are instructed to soak the plant leave in hot water about (80oC). They should then drink half a glass (about 0.25l) two times daily for 4-7 days. Smaller doses are prescribed for children according to their weight.They are used as vegetable and stimulate the digestive system in some other countries in the continent.

 This plant has ethnomedical use in treating veneral diseases, gastrointestinal problems and malaria (Kambizi et al, 2001; Huffman et al, 2003; Hamill et al, 1992). Furthermore, they are used as local medicine against leech, which are transmitting bilharzias. Free living chimpanzees eat the leaves, if they have attacked by parasites (Huffman, M.A. 2003). There are reports concerning the hypoglycaemic, antineoplastic antibacterial and antioxidant properties of the plant. (Akah et al, 1992; Izevbigie et al, 2004; Taiwo et al, 1999; Iwalewa et al, 2005). Despite the varied uses of the plant, there are no information on its analgesic properties and exact toxicology on sub-chronic exposure, although some reports describe its antiplasmodial effects (Abosi et al 2005; Masaba et al 2000; Tona et al, 2004; Wilcox et al, 1999). Previous phytochemical reports have shown the presence of steroid, saponins, flavonoids.
