文章基本信息

标题：Epicatechin Gallate as Xanthine Oxidase Inhibitor: Inhibitory Kinetics, Binding Characteristics, Synergistic Inhibition, and Action Mechanism
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作者：Miao Zhu ; Junhui Pan ; Xing Hu 等
期刊名称：Foods
电子版ISSN：2304-8158
出版年度：2021
卷号：10
期号：9
DOI：10.3390/foods10092191
语种：English
出版社：MDPI Publishing
摘要：Epicatechin gallate (ECG) is one of the main components of catechins and has multiple bioactivities. In this work, the inhibitory ability and molecular mechanism of ECG on XO were investigated systematically. ECG was determined as a mixed xanthine oxidase (XO) inhibitor with an IC 50 value of 19.33 ± 0.45 μM. The promotion of reduced XO and the inhibition of the formation of uric acid by ECG led to a decrease in O 2− radical. The stable ECG–XO complex was formed by hydrogen bonds and van der Waals forces, with the binding constant of the magnitude of 10 4 L mol −1, and ECG influenced the stability of the polypeptide skeleton and resulted in a more compact conformation of XO. Computational simulations further characterized the binding characteristics and revealed that the inhibitory mechanism of ECG on XO was likely that ECG bound to the vicinity of flavin adenine dinucleotide (FAD) and altered the conformation of XO, hindering the entry of substrate and the diffusion of catalytic products. ECG and allopurinol bound to different active sites of XO and exerted a synergistic inhibitory effect through enhancing their binding stability with XO and changing the target amino acid residues of XO. These findings may provide a theoretical basis for the further application of ECG in the fields of food nutrition and functional foods.
关键词：enxanthine oxidase;epicatechin gallate;synergistic inhibition mechanism;superoxide anion;molecular dynamics simulation