Isolation and Characterization of Prophylactic Antimalarial Agents from Ochna kibbiensis Leaves

Abstract

Ochna kibbiensis (Family: Ochnaceae) has been employed in ethnomedicine for the treatment of malaria and inflammation, among others. The aim of this study was to isolate and characterize prophylactic antimalarial agents from the leaves of O. kibbiensis against Plasmodium berghei, in vivo and in silico. The median lethal dose (LD50) of the methanol extract and its fractions (hexane, dichloromethane, ethylacetate and butanol) was determined according to Lorke’s method while the antimalarial effect of the extract and its fractions was investigated according to the method described by Peters prophylactic test using Chloroquine-sensitive Plasmodium berghei (NK65). All the extract/fractions exhibited LD50 values ≥ 5000 mg/kg with the exception of the n-butanol fraction (1702.94 mg/kg), which indicate that the plant is non-toxic. Dichloromethane fraction exhibited a significant (p < 0.05) and dose-dependent prophylactic effect with 47.62, 85.12, and 100.0% prophylaxis (at 500, 250, and 125 mg/kg), while the least effect was observed by the butanol fraction with a percentage prophylaxis of 64.29 and 76.19, respectively; the standard drug, pyrimethamine, had 95.24% prophylaxis. Based on the results obtained, dichloromethane fraction of O. kibbiensis was subjected to chromatographic purification, which led to the isolation of a mixture of two compounds identified as stigmasterol and β-sitosterol by analysis of the NMR spectral data and comparison with existing literature; the compounds exhibited good binding affinities (−5.129 and −4.889 kcal/mol) against pfLDH and a favorable ADMET profile. In conclusion, the leaves of O. kibbiensis have demonstrated a significant prophylactic antimalarial activity and the two known steroids (stigmasterol and β-sitosterol) were isolated from the dichloromethane fraction for the first time.