Antiplasmodial activity, Toxicity and Phytochemistry of Selected Plant Species used by Rukararwe and Prometra Herbalists in Treatment of Malaria in Uganda

Abstract

Resistance of malaria parasites to known antimalarial drugs necessitated to finding new drugs from natural products which are readily available to treat malaria. The study documented; medicinal plants used in malaria treatment by Traditional Herbalists of Prometra and Rukararwe, determined antiplasmodial activity and toxicity, and characterised isolated chemical structures of the compounds. The selected plant species were identified from ethnobotanical surveys. Micro Mark III test was used for in vitro antiplasmodial analysis of the extracts and some pure compounds. Acute and sub-chronic toxicity was done on Wister mice and Albino rats. A combination of chromatographic techniques were used to isolate pure compounds and their chemical structures were determined using spectroscopic techniques. 86 and 54 plant species were used in malaria treatment by Prometra and Rukararwe Herbalists respectively. Clerodendrum rotundifolium (leaves) and Zanthoxylum chalybeum (stem bark) were selected for further investigation. The most active extracts against Plasmodium falciparum from Z. chalybeum and C. rotundifolium had IC50 values of ≤ 0.03 µg/mL and the water extracts had very low toxicity values (LD50 20,216 mg/kg and 8,300mg/kg) respectively. A dose of 200 mg/kg of the water extract of C. rotundifolium was found to be safe for use. Fagaramide from Z. chalybeum, Verbascoside and Quercetin from C. rotundifolium were isolated and elucidated with IC50 values of 2.85 µg/ml, IC50 17.0 µg/ml and IC50 27.0 µg/ml respectively against P. falciparum. The findings indicate that the selected plants are efficacious and non-toxic which justifies their use in malaria treatment. The isolated compounds are potential antiplasmodial agents for the discovery of new natural antimalarial compounds. The compounds can also be used as markers in the formulation of antimalarial herbal remedies from these plants.