Inhibitory mechanism of vitexin on α-glucosidase and its synergy with acarbose

Vitexin, a C-glycosylated flavonoid , is abundant in numerous foods . In this study, vitexin was determined as an uncompetitive α-glucosidase inhibitor and its binding site was different from the active site. It possessed a remarkably higher inhibitory activity than acarbose with its IC 50 value of 52.80 ± 1.65 μM. Interestingly, the combination of acarbose with vitexin showed a strong synergistic inhibition effect. The stable complex between vitexin and α-glucosidase was mainly formed by hydrogen bonds and hydrophobic forces. The presence of vitexin induced a looser conformation of α-glucosidase and decreased its surface hydrophobicity. Computational docking and chemical modification of α-glucosidase found that residues Glu, Asn, Lys, and Thr were essential for the binding course and their importance order was Glu, Asn > Lys > Thr. Molecular dynamics simulation results revealed the molecular mechanism of the interaction between vitexin and α-glucosidase and verified the above experimental results. This work proposed rewarding findings in functional research of vitexin as a potential α-glucosidase inhibitor.