Inhibition of Bungarus caeruleus snake venom toxicity by Citrus reticulata methanolic extract and in-silico analysis of possible binding modes

Abstract

Snakebite envenomation has been one of the major causes of morbidity and mortality around the world. Though intravenous administration of commercial anti-venom systemically neutralizes the toxicity, adverse effects are commonly seen in the post-treatment period. Plant metabolites and their derivatives have been shown to exhibit a wide range of anti-ophidian properties. In this study, we have investigated the Bungaruscaeruleus venom neutralization potential of Citrus aurantium and Citrus reticulata Blanco peels in terms of phospholipase and hemolytic inhibition. Methanolic extract of C. reticulata exhibited the highest inhibition (93%) of PLA₂ activity. However, the extracts of both these Citrus species significantly inhibited the hemolytic activity of the venom (54–82%). Molecular docking indicated the binding of the citrus metabolites to catalytic site residues (TRP19, GLY30, TYR31, GLY32, and HIS48) of PLA₂. In vivo studies using Swiss Albino mice confirmed the neutralising capacity of the citrus peel extract, as reflected by the increase in survival time. Therefore, the study reveals that these metabolites in the methanolic extract of the citrus peel can be used as supplements for the management of snake bites.