Inhibition effects of xanthohumol on α-amylase and α-glucosidase: Kinetics, multi-spectral and molecular docking

Abstract

α-Amylase and α-glucosidase, two therapeutic targets for diabetes management, play crucial roles in carbohydrate metabolism and glucose absorption. Xanthohumol, one chalcone derived from hops, has demonstrated potential as a natural healthy phytonutrient. But its inhibition effects against α-amylase and α-glucosidase were still unclear. This study employs a comprehensive analytical strategy, including kinetics, multi-spectral, and molecular docking methods, to dissect the inhibition effects of xanthohumol against α-amylase and α-glucosidase. Our findings indicated that xanthohumol exerted a reversible mixed-type inhibition on both enzymes, with IC₅₀ values of 71.07 ± 5.82 μM for α-amylase and 32.58 ± 3.11 μM for α-glucosidase. Multi-spectral analyses (fluorescence quenching, synchronous fluorescence, 3D fluorescence, ANS-binding fluorescence, and CD) revealed that xanthohumol binding induced conformation changes and microenvironment alterations in the enzymes, thereby inhibiting their activities. Molecular docking and dynamics studies further substantiated the interaction forces between xanthohumol and the enzymes. This research provided insights into the effects of xanthohumol as an inhibitor of α-amylase and α-glucosidase, offering valuable data to support the development of xanthohumol as a natural therapeutic for diabetes management.