Rutin Ameliorates Malaria Pathogenesis by Modulating Inflammatory Mechanism: An In-Vitro and In-Vivo Study

Abstract

Rutin (3,3’,4’ 5,7-pentahydroxyflavone-3-rhamnoglucoside) is a flavonoid glycoside, found in many edible plants such as buckwheat and berries. Rutin as a food supplement is recommended for the treatment of various diseases, which directed us to investigate its valuable effects in malaria induced pathogenesis. In the present study, Rutin was tested for its anti-plasmodial activity against chloroquine sensitive and resistant strains (NF-54 and K1) of Plasmodium falciparum and studied for its anti-oxidative and anti-inflammatory potential against LPS stimulated macrophage cells. In vitro observations were further validated using an in-vivo physiological rodent model of Plasmodium berghei-induced malaria pathogenesis. Rutin was also tested for its effect in combination with chloroquine.Rutin was found to have potent anti-plasmodial activity against both chloroquine sensitive and resistant strains of P. falciparum (NF-54 and K1). It was able to reduce the oxidative stress induced by LPS in macrophage cells with decreased production of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β). Rutin was found to significantly suppress the parasitaemia, increase the mean survival time and restored the haemoglobin and glucose level in in vivo assays. This was corroborated by reduced production of malondialdehyde (MDA) and pro-inflammatory mediators in rutin treated mice in P.berghei-induced malaria pathogenesis. Interestingly, the combination of rutin with chloroquine had shown synergy in both in vitro and in vivo experiments. The findings of the present study thus highlighted the suitability of rutin for further study in the management of drug resistant malaria, alone or in combination with other compounds.