α-Glucosidase inhibition activity and mechanism of phenolic compounds extracted from Gleditsia sinensis Lam.

Inhibiting α-glucosidase activity by secondary metabolites has been confirmed as an effective strategy for treating type 2 diabetes mellitus (T2DM). α-Glucosidase inhibitory activity was determined by different parts of Gleditsia sinensis Lam. (GSL) extracts. The thorn of the GSL methanol extract exhibited the highest activity (IC 50  = 0.21 mg/mL). Eleven potential α-glucosidase inhibitors were detected by Ultra Performance Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry, and fisetin was screened as the dominant compound (IC 50  = 0.211 µM) through virtual screening, correlation analysis, and inhibitory assay. Fluorescence quenching experiment explained that fisetin inhibited α-glucosidase through hydrogen bonds and hydrophobic forces in a reversible and non-competitive mode. Three-dimensional fluorescence and circular dichroism demonstrated that fisetin modified the amino acids’ microenvironment and disrupted the hydrogen-bonded network of α-glucosidase. α-Glucosidase was bounded with fisetin by hydrogen (Thr448, His515, Asp346, and Gln531) and hydrophobic residues (His515, Lys352, and Ala349) simulated by molecular docking. This study points out the fisetin’s inhibitory mechanism of α-glucosidase, indicating that it is a promising natural ingredient in T2DM treatment.