An Insight Into the Inhibitory Mechanisms of Hesperidin on α-Glucosidase Through Kinetics, Fluorescence Quenching and Molecular Docking Studies

The α-glucosidase inhibitor is of interest to researchers due to its association with type-II diabetes treatment by suppressing postprandial hyperglycemia. Hesperidin is a major flavonoid in orange fruit with diverse biological properties. This paper evaluates the effects of hesperidin on α-glucosidase through inhibitory kinetics, fluorescence quenching, and molecular docking methods for the first time. The inhibition kinetic analysis showed that hesperidin reversibly inhibited the α-glucosidase activity with an IC50 value of 18.52 M and the inhibition was performed in an uncompetitive type. Fluorescence quenching studies indicated that the intrinsic fluorescence of α-glucosidase was quenched via a static quenching process and only one binding site was present between hesperidin and α-glucosidase. The interaction between them was spontaneous and mainly driven by hydrogen bonds as well as hydrophobic forces. Furthermore, molecular docking results suggested that hesperidin might bond to the entrance or outlet part of the active site of α-glucosidase through a network of five hydrogen bonds formed between hesperidin and the four amino acid residues (Trp709, Arg422, Asn424, and Arg467) of ?-glucosidase and hydrophobic effects. These results provide new insights into the inhibitory mechanisms of hesperidin on α-glucosidase, supporting the potential application of hesperidin-rich orange product as a hypoglycemic functional food.