Pithayanukul Pimolpan, Leanpolchareanchai Jiraporn, Saparpakorn Patchreenart
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Molecules. 2009 Aug 27;14(9):3198-213. doi: 10.3390/molecules14093198.
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 Zn(2+) atom of the SVMPs, which could potentially result in inhibition of the venom enzymatic activities and thereby inhibit tissue necrosis.
蛇咬伤中毒会导致严重的局部组织坏死,毒液金属蛋白酶被认为是其中的关键毒素。在本研究中,泰国芒果(芒果属印度种‘法伦’)(漆树科)种仁的乙醇提取物及其主要酚类成分(五倍子酰葡萄糖)在体外试验中对马来亚蝰蛇和泰国眼镜蛇毒液的酪蛋白水解和纤维蛋白原水解活性表现出强效且剂量依赖性的抑制作用。分子对接研究表明,酚类成分的结合方向位于蛇毒金属蛋白酶(SVMPs)的结合口袋中。酚类成分可与保守锌结合基序中的三个组氨酸残基形成氢键,并能螯合SVMPs的Zn(2+)原子,这可能会抑制毒液的酶活性,从而抑制组织坏死。