Exploring the inhibitory mechanism of piceatannol on α-glucosidase relevant to diabetes mellitus

Due to their association with type 2 diabetes mellitus treatment, alpha-glucosidase inhibitors have attracted increasing attention of researchers. In this study, we systemically investigated the kinetics and inhibition mechanism of piceatannol on alpha-glucosidase. Enzyme kinetics analyses showed that piceatannol exhibited strong inhibition on alpha-glucosidase in a non-competitive manner. Spectroscopy analyses indicated that piceatannol could bind with alpha-glucosidase to form complexes via high affinity. Further, computational molecular dynamics and molecular docking studies validated that the binding of piceatannol was outside the catalytic site of alpha-glucosidase, which would induce conformational changes of alpha-glucosidase and block the entrance of substrate, causing declines in alpha-glucosidase activities. Our results provide useful information not only for the inhibition mechanism of piceatannol against alpha-glucosidase but also for a novel target site for developing novel alpha-glucosidase inhibitors as potential therapeutic agents in the treatment of type 2 diabetes mellitus.