Antiplasmodial Activities And In Vivo Safety Of Extracts And Compounds Of Seven Indigenous Kenyan Medicinal Plants Used Traditionally To Treat Malaria

ABSTRACT

Among human parasitic diseases, malaria is the most important and it has global incidence of 300 to 500 million cases per year with about 1.5 million deaths among African children. Recently the disease has been subjected to massive control efforts with varying degrees of success. The development of parasite and vector resistance to conventional drugs and insecticides has complicated both treatment and control today. The main goal of this project was to identify viable phytomedicines traditionally employed for the treatment of malaria in Kenya that could be developed into antimalarial agents. Seven medicinal plants used by herbalits in Kilifi and Homa-Bay Counties were examined: Achyranthes aspera, Heinsia crinita, Bridelia cathartica, Citrus limon, Microglossa pyrifolia, Vernonia glabra and Carissa edulis. Both organic and aqueous plant extracts were obtained and tested for antiplasmodial activity against CQ sensitive and resistant strains of P.falciparum in vitro. Active extracts were subjected to bioactivity guided fractionation and isolation of compounds. Structural elucidation of isolated compounds was determined using standard spectroscopic techniques (IR, NMR & MS). The most active plant extracts against P. falciparum had the following IC50 activities: DCM extract of Citrus limon roots (7.017 μg/ml), aqueous extract of Carissa edulis roots (8.054 μg/ml), DCM and methanolic extracts of Bridelia cathartica leaves (11.537 μg/ml, 15.647 μg/ml) respectively and DCM extract of Heinsia crinita leaves (13.336 μg/ml). The others were as follows: hexane extract of Achyranthes aspera leaves (18.087 μg/ml), hexane extract of Microglossa pyrifolia leaves (21.376 μg/ml), methanolic extract of Heinsia crinita leaves (24.805 μg/ml), aqueous extract of Bridelia cathartica leaves (25.985 μg/ml), and DCM extract of Carissa edulis roots (30.074 μg/ml). Toxicity tests on crude DCM root extract of C. limon, indicated that 70% of the biochemical parameters studied using the rabbit model were not affected. Two pure coumarin compounds, suberosin (IC50 53.1415μg/ml ά D6 strain of P. falciparum, 26.732μg/ml ά W2 strain) and xanthyletin (IC50 1580μg/ml ά W2 strain) were isolated from C. limon. Spinasterol (IC50 43.169 μg/ml ά V1/S strain) was isolated for the first time from hexane leaf extract of Microglossa pyrifolia. Histology of the liver, heart, kidney and brain did not reveal any damage. Citrus limon is a potential antimalarial drug and owes its activity to the presence of suberosin and other compounds with which it works in synergy against falciparum. In conclusion, there were no significant toxic effects on rabbit tissue observed upon treatment with the crude DCM root extract of C. limon in the subchronic toxicity studies as about 90% of the parameters examined were not affected. Therefore a drug that can cure malarial infection can be synthesized modelled upon the structure of suberosin. Quinine and mefloquine have structures which are closely related to this compound. Further studies on C. limon required to be carried out in order to isolate and identify more compounds and test them against falciparum. In addition, compound isolation from aqueous extracts of C. edulis which also demonstrated high activity against P. falciparum requires to be carried out. This study has verified the use of these plants for the treatment of malaria by the traditional communities.