Molecular Docking Studies and Anti−Snake Venom Metalloproteinase Activity of Thai Mango Seed Kernel Extract

Pimolpan Pithayanukul,Jiraporn Leanpolchareanchai,Patchreenart Saparpakorn

doi:10.3390/molecules14093198

Pimolpan Pithayanukul, Jiraporn Leanpolchareanchai + Show 1 more

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https://doi.org/10.3390/molecules14093198

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Journal: Molecules	Publication Date: Aug 27, 2009
Citations: 70	License type: CC BY 4.0

Affiliation: Mahidol University, Kasetsart University

Abstract

Snakebite envenomations cause severe local tissue necrosis and the venom metalloproteinases are thought to be the key toxins involved. In this study, the ethanolic extract from seed kernels of Thai mango (Mangifera indica L. cv. ‘Fahlun’) (Anacardiaceae) and its major phenolic principle (pentagalloylglucopyranose) exhibited potent and dose−dependent inhibitory effects on the caseinolytic and fibrinogenolytic activities of Malayan pit viper and Thai cobra venoms in in vitro tests. Molecular docking studies revealed that the binding orientations of the phenolic principles were in the binding pockets of snake venom metalloproteinases (SVMPs). The phenolic principles could form hydrogen bonds with the three histidine residues in the conserved zinc−binding motif and could chelate the Zn2+ atom of the SVMPs, which could potentially result in inhibition of the venom enzymatic activities and thereby inhibit tissue necrosis.

Highlights

Snakebite envenomations constitute a relevant public health hazard in remote areas of Thailand since the economic activities in these areas are mainly agricultural
Snake venom metalloproteinases (SVMPs) are responsible for degrading extracellular matrix (ECM)
From the in vitro test, the initial caseinolytic doses of Calloselasma rhodostoma Kuhl (CR) and naja kaouthiaLesson (NK) venoms obtained from the plot between venom doses and their caseinolytic activity were 50 and 500 μg, respectively

Summary

Introduction

Snakebite envenomations constitute a relevant public health hazard in remote areas of Thailand since the economic activities in these areas are mainly agricultural. Among the many venomous snakes found in Thailand, CR and NK venoms cause the most severe local tissue damage on the bite site. Snake venoms are complex mixtures and are comprised mainly of proteins and peptides possessing a variety of biological activities. Snake venom metalloproteinases (SVMPs) are the only venom components that possess hemorrhagic activity and are both direct [3] and indirect [4] mediators of local tissue damage, such as hemorrhage, edema, myonecrosis, dermonecrosis and inflammation following envenoming. Most of the venom metalloproteinases are fibrinogenolytic enzymes, cleaving preferentially the A chain and slowly the B chain of fibrinogen [5].

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