Antimalarial activity of some plants traditionally used in treatment of Malaria in Kwale and Meru districts

Abstract

Plasmodium falciparum, the commonest etiological agent for human malaria is becoming increasingly resistant to commonly used drugs like chloroquine (CQ), which was efficacious, available, affordable and of low toxicity. Therapeutic regimens for prevention and treatment, of CQ resistant P. falciparum are associated with higher costs and side effects compared to CQ. Efforts are being directed towards obtaining new drugs with different structural features. The success of artemisinin, a sesquiterpene lactone from Chinese traditional medicine which has a different chemical structure from quinine has stimulated the search for new antimalarial drugs from traditional antimalarial remedies. Since many modern drugs originated from plants, the investigation of chemical components of traditional medicinal plants could lead to development of new effective, affordable and safe antimalarial drugs. Kenya, with its rich floral resources and ethnobotanical history is an ideal place to document and screen plants for antiplasmodial activities. Sixty four medicinal plants with a traditional reputation for their use against malaria were collected and documented from two study sites at Meru and Kwale districts. 15 plant species were selected for antimalarial assays. 15 methanolic and 15 water extracts from these plants were screened for their in vitro antiplasmodial activities by inhibition of radio labeled uptake of hypoxanthine by CQ sensitive (D6) and resistant (W2) P. falciparum clones. They were also screened for their antimalarial activities in vivo in a 4- Day suppressive test using mice infected with P. berghei strain ANKA. Animal acute toxicity and cell cytotoxicity using Vero E6 cells was carried out on all the extracts. Of the 15 methanolic extracts tested for antiplasmodial activity, 10 (67%) had IC5O<20mg/ml for W2 and D6 sensitivity. The water extracts were less active. For the same 15 methanolic extracts, 10 (67%) had a chemo suppression >50% while 6 (40%) water extracts had chemo suppression >50%. Half of the water extracts were inactive in vitro, but active in vivo suggesting a prodrug effect. Four methanol and four water extracts gave survival times which were similar to that of mice treated with CQ (p>0.05). The CQ sensitive clone was more susceptible to the extracts than the CQ resistance clone. The ratio between the two, for some of the extracts, was less than that of CQ reference drug suggesting no cross-resistance to CQ. Almost all the extracts tested for acute toxicity were safe with LD5O>5000 mg/kg body weight and the selectivity index (SI) of the extracts was high indicative of non-toxicity. These findings seem to confirm the validity of these plants for traditional treatment of malaria and a possibility of activity-guided isolation of active principles from the bioactive extracts.