Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Antimalarial activity and safety assessment of Flueggea virosa leaves and its major constituent with special emphasis on their mode of action.

PMID 28273638


A clinical emergency stands due to the appearance of drug resistant Plasmodium strains necessitate novel and effective antimalarial chemotypes, where plants seem as the prime option, especially after the discovery of quinine and artemisinin. The present study was aimed towards bioprospecting leaves of Flueggea virosa for its antimalarial efficacy and active principles. Crude hydro-ethanolic extract along with solvent derived fractions were tested in vitro against Plasmodium falciparum CQ sensitive (3D7) and resistant (K1) strains, where all the fractions exhibited potential activity (IC50 values <10μg/mL) against both the strains. Interestingly, under in vivo conditions against P. berghei in Swiss mice, preferential chemo-suppression was recorded for crude hydro-ethanolic extract (77.38%) and ethyl acetate fraction (86.09%) at the dose of 500mg/kg body weight. Additionally, ethyl acetate fraction was found to be capable of normalizing the host altered pharmacological parameters and enhanced oxidative stress augmented during the infection. The bioactivity guided fractionation lead to the isolation of bergenin as a major and active constituent (IC50, 8.07±2.05μM) of ethyl acetate fraction with the inhibition of heme polymerization pathway of malaria parasite being one of the possible chemotherapeutic target. Furthermore, bergenin exhibited a moderate antimalarial activity against P. berghei and also ameliorated parasite induced systemic inflammation in host (mice). Safe toxicity profile elucidated through in vitro cytotoxicity and in silico ADME/T predications evidently suggest that bergenin possess drug like properties. Hence, the present study validates the traditional usage of F. indica as an antimalarial remedy and also insists for further chemical modifications of bergenin to obtain more effective antimalarial chemotypes.

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