Background: The suppression of α-glucosidase activity to retard glucose absorption is an important therapy for type-2 diabetes. Corosolic acid (CRA) is a potential antidiabetic component in many plant-based foods and herbs. In this study, the interplay mechanism between α-glucosidase and corosolic acid was investigated by several methods, including three-dimensional fluorescence spectra, circular dichroism spectra, and molecular simulation.
Results: Corosolic acid significantly inhibited α-glucosidase reversibly in an uncompetitive manner and its IC50 value was 1.35 × 10-5 mol L-1 . A combination of CRA with myricetin exerted a weak synergy against α-glucosidase. The intrinsic fluorescence of α-glucosidase was quenched via a static quenching course and the binding constant was 3.47 × 103 L mol-1 at 298 K. The binding of CRA to α-glucosidase was mainly driven by hydrophobic forces and resulted in a partial extension of the protein polypeptide chain with a loss of α-helix content. The molecular simulation illustrated that CRA bound to the entrance part of the active center of α-glucosidase and interacted with the amino acid residues Ser157, Arg442, Phe303, Arg315, Tyr158, and Gln353, which could hinder the release of substrate and catalytic reaction product, eventually suppressing the catalytic activity of α-glucosidase.
Conclusions: These results may suggest new insights into corosolic acid from food sources as a potential α-glucosidase inhibitor that could better control diabetes. © 2019 Society of Chemical Industry.
Keywords: corosolic acid; inhibition mechanism; isobologram; synergy; uncompetitive inhibitor; α-glucosidase.
© 2019 Society of Chemical Industry.