Anti-Malarial Activity and Toxicological Effect of Combined Corymbia Citriodora, Maytenus Senegalensis and Warbugia Ugandensis as Used in Traditional Medicine in Kenya

Malaria is majorly caused by Plasmodium falciparum resulting in thousands of deaths every year. In Africa, it is a key contributor to the disease burden notable in the disability adjusted life years (DALYs). About 243 million individuals are at a risk of contracting the disease and a higher rate of deaths are observed in children under the age of five. Conventional drugs are available at a subsidized rate but the rising problem is the resistance of the plasmodium parasite to these drugs. Hence, there is an urgent need for the development of new and alternative therapeutics for treatment of malaria. In some regions in Kenya, parts of locally available plants are harvested and used for treating malaria. It is estimated that locally, 30% of the population relies on traditional medicine for treating various ailments due to the lack of infrastructure and accessible medical facilities especially in the rural areas. Warbugia ugandensis , Maytenus senegalensis and Corymbia citriodora are amongst the plants used in herbal medicine for the treatment of malaria. However, their combinatorial antimalarial efficacy and safety is yet to be determined hence the aim of this study. The plants were harvested from their natural habitats and transported to the Centre of Traditional Medicine and Drug Research (CTMDR) at the Kenya Medical Research Institute (KEMRI), Nairobi. Antimalarial properties of single and combined extracts were analyzed against Plasmodium berghei in vivo . Cytotoxic properties of the plants were carried out against the vero cell-lines in vitro by the MTT assay. Acute oral toxicity was conducted according to the OECD protocol. Effective concentration (ED 50 ), cytotoxicity concentration (CC 50 ) and median lethal dose (LD50) were derived. The result indicated that the combination of M. senegalensis: W. ugandensis (1:1) had the most antimalarial activity at ED 50 of 1.05mg/kg whereas among the single plants W. ugandensis had the highest antimalarial activity (ED 50 of 3.3mg/kg). The combinations of C. citriodora : M. senegalensis : W. ugandensis (1:1:1), C. citriodora : M. senegalensis : W. ugandensis (1:0.5:1) and C. citriodora : M. senegalensis : W. ugandensis (0.5:1:0.5) showed cytotoxicity concentration (CC 50 ) of 101.47±3.17 µg/ml, 213.55±3.47 µg/ml and 575.80±31.40 µg/ml respectively. A ll the plants combinations showed no cytotoxic effects. The synergistic antimalarial properties of combined C. citriodora : M. senegalensis , C. citriodora : W. ugandensis and M. senegalensis : W. ugandensis were confirmed as the extracts showed SFIC indexes of 0.67, 0.83 and 0.28 respectively. All the plant extracts demonstrated LD 50 above 2000 mg/kg with no adverse effects hence recognized as safe. This study confirms the safety and antimalarial activities of these plants and justify their use in herbal medicine practices. The results of this study sets the precedence for the development of an antimalarial herbal formulation that is less toxic and more affordable.