Cysteine Protease Inhibitors from Calotropis procera with Antiplasmodial Potential in Mice

Abstract

Inhibitory activity of crude extract of cysteine protease inhibitors from Calotropis procera against Plasmodium berghei infected mice was investigated. Various extracts obtained from the leaves, roots, flowers, latex and stem bark of Calotropis procera using different extraction media that included Sodium Chloride, Sodium Hydroxide, Hydrochloric acid, Sodium phosphate buffer and distilled water were used to evaluate for Cysteine Protease inhibitory activity against Papain enzyme. Sodium phosphate buffer extract of the latex of Calotropis procera with the highest Protease inhibitor activity was concentrated by cold acetone precipitation, freeze-dried and used for further studies. Subchronic toxicity study of the extract was carried out in a mouse model. Inhibitory effect of the extract on Plasmodium berghei Cysteine protease and in vivo studies on infected mice was investigated using incremental doses of 20, 30, and 50 mg/kg body weight/day. The crude extract exhibited inhibitory activity against Cysteine protease with an IC50 value of 25.50 µg/ml. The highest percentage parasite suppression of 48% was obtained for the group treated with 50 mg/kg bodyweight/day of the extract. Subchronic toxicity study using the effective dose of the extract at 50 mg/kg body weight/day showed a significant elevation in body weight of the animals and Alanine transaminase activity. A dose-dependent relationship was observed in the elevation of total protein and glucose concentrations in treated animals, but there were no significant changes in percentage PCV, triacylglycerol concentration, Aspartate transaminase and Alkaline Phosphatase activities. The result of this study shows that crude extract obtained from Latex of Calotropis procera is active against plasmodium Cysteine Protease in rodent malaria model and could be considered as a potential source for antimalarial drug development.