Proteins make tea polyphenol EGCG not always develop satisfactory α-glucosidase inhibition: The influences of three proteins on α-glucosidase inhibitory activity of EGCG

Abstract

Tea polyphenol epigallocatechin-3-gallate (EGCG) has been previously explored as an effective inhibitor of carbohydrate hydrolyzing α-glucosidase for regulating postprandial blood glucose level. Proteins act as one common dietary component, the influence of which on α-glucosidase inhibition of EGCG remains unknown. In this study, bovine serum albumin (BSA) and isolated whey protein (IWP) were found to significantly weaken the competitive inhibitory activity of EGCG against α-glucosidase by the effect order of BSA > IWP, while egg albumin (EA) hardly influenced the enzyme inhibition. Through the analyses of kinetics, spectroscopy, thermodynamics and simulated docking, a protein-EGCG-enzyme ternary complex was suggested to generate in the interaction system, in which there existed competition between proteins (BSA and IWP) and α-glucosidase regarding formation of hydrogen bondings with polyphenolic groups (especially galloyl moiety). This weakened the EGCG-enzyme binding interactions at α-glucosidase active site, and thus reduced the enzyme inhibition in vitro and in vivo. However, there existed a co-existing relationship between proteins and α-glucosidase regarding π-stackings of EGCG benzene ring with aromatic residues of both macromolecules, which remained the fluorescence quenching ability of EGCG against the enzyme. Conclusively, dietary proteins should be considered as a potential influence factor when developing natural products as inhibitors of carbohydrate hydrolyzing enzymes.