Co-administration effects and toxicity profile of ethyl acetate fraction of Stemonocoleus micranthus Harms and Artesunate in murine malaria model

Abstract

The increasing reports of multi-drug resistant malaria has necessitated the continuous search for new drug candidates, enhancing the efficacy and life span of existing agents. The study aims at evaluating antimalarial potentials and safety use of ethyl acetate fraction of Stemonocoleus micranthus Harms (SM-EF) in co-administration with antimalarial artesunate. Ethyl acetate fraction from 80% methanolic leaf extract was investigated for antimalarial activity in single and combination with different doses of artesunate (2.5, 5 and 10 mg kg_1) against Plasmodium berghei in mice. The parameters measured were curative effect against established infection, mean survival time (MST), weight loss, rectal temperature changes and packed cell volume (PCV). Histopathological study was done on concerned internal organs. The daily monitored curative effect of SM-EF used singly and in combination with artesunate showed a daily, dose-dependent and progressively reduction of malaria parasite. Ethyl acetate fraction of Stemonocoleus micranthus Harms used alone showed a poor onset of activity but long acting effect. On day 9, percentage inhibition effect was 86.78, 85.42, 92.98, 100, 91.19 and 100% for SM-EF, SM-EF-artesunate 2.3, 5 and 10 mg kg-1, artesunate 10 mg kg_1 and chloroquine 10 mgkg_1 respectively. Highest MST was chloroquine (21 days) and SM-EF-artesunate 10 mg kg_1 (19.5 days). Safety study of the harvested organs showed no untoward effect. The combination of SM-EF with artesunate 10 mg kg_1, showed an enhanced antimalarial activity. This study supports the basis for the suggestion of SM-EF as a prospective drug candidate in antimalarial drug combinations regimen.