Anti-malarial Effect of Momordica charantia Involved Modulation of Cytokine Mediated via GSK3β Inhibition in Plasmodium berghei- Infected Mice.

Increasing resistance of malarial parasites to current anti-malarials has led to efforts to explore use of medicinal plants as immunomodulators to target the host. Momordica charantia(MC) is an Asian dietary fruit with different pharmacological activities. GSK3 is known to be pivotal in the controlling of cytokine inflammatory response. Present investigation involves evaluation of MC aqueous extract for its anti-malarial activity and to elucidate whether its mechanism involves inhibition of GSK3β. Akt and NF-κB in the action of MC on GSK3 were evaluated. Our in vitro studies using Plasmodium falciparum 3D7 culture revealed that MC suppressed parasite growth with a selectivity index exceeding 10. Intra-peritoneal administration of the aqueous extract into P. berghei NK65-infected mice resulted in a dose-dependent manner and improved median survival time. The selected doses of MC into infected mice resulted in significant increase in the levels (7.2 and 2.7fold) of phosphorylated GSK3β and Akt respectively in liver. Decreased phosphorylation of NF-κB (2.0fold) in MC-treated infected mice was observed. MC decreased levels of the serum pro-inflammatory cytokines IFN-γ(2.7fold), TNF-α (4.9fold), while the anti-inflammatory cytokine level IL-10 was increased (2.3fold). Our findings demonstrate that anti-malarial effect of MC involved cytokine modulation mediated via inhibition of GSK3β in P. berghei- infected mice. [ABSTRACT FROM AUTHOR]