α-Glucosidase inhibitory effect of anthocyanins from Cinnamomum camphora fruit: Inhibition kinetics and mechanistic insights through in vitro and in silico studies

alpha-Glucosidase inhibitors are widely used to suppress postprandial glycemia in the treatment of type 2 diabetes mellitus. The present study evaluated the in vitro alpha-glucosidase inhibitory activity of three major pigment constituents of Cinnamomum camphora fruit, namely cyanidin, cyanidin 3-rutinoside, and cyanidin-3-O-glucoside. We found that cyanidin exerted strong inhibitory activity on alpha-glucosidase, with IC50 of 5.293 x 10(-3) mM, whereas cyanidin 3-rutinoside and cyanidin-3-O-glucoside did not show inhibitory activity on alpha-glucosidase. The inhibitory activity of cyanidin was stronger than that of acarbose (10(50) 1.644 mM), the current most commonly used drug for postprandial glycemia. Kinetic analysis indicated that cyanidin inhibited alpha-glucosidase through competition, with a K-1 value of 0.0183 mM. Fluorescence spectrum titration showed only one binding site between cyanidin and alpha-glucosidase, and the binding constant was calculated. Further, molecular docking was conducted to simulate the binding interactions between cyanidin and alpha-glucosidase. Cyanidin was found to interact with several residues close to the catalytic site of alpha-glucosidase through pi-pi stack interaction and hydrogen bonds. The calculated binding energy of the cyanidin and enzyme complex was - 105.031 kJ/mol. Molecular simulation and calculation showed that the van der Waals force played an essential role in the binding of alpha-glucosidase and cyanidin. (C) 2019 Elsevier B.V. All rights reserved.