Inhibitory mechanism of sinensetin on α-glucosidase and non-enzymatic glycation: Insights from spectroscopy and molecular docking analyses.

Inhibition of α-glucosidase and non-enzymatic glycation is regarded as an effective method to prevent and treat type 2 diabetes and its complications. In this study, the inhibition of sinensetin on α-glucosidase and non-enzymatic glycation was studied with multi-spectroscopic techniques and molecular docking analysis. The results of fluorescence spectroscopy analysis indicated that sinensetin quenched the endogenous fluorescence of α-glucosidase in static manner. The binding of sinensetin with α-glucosidase was a spontaneous process primarily driven by hydrophobic interaction. At 298 K, the binding constant was (5.70 ± 0.12) × 104 L·mol−1 and the binding site number was 1. The conformation of α-glucosidase was altered by sinensetin, which was revealed by circular dichroism (CD), FTIR spectra, synchronous fluorescence and three-dimensional (3D) fluorescence spectroscopy methods. Molecular docking analysis demonstrated that sinensetin interacted with the amino acid residues of α-glucosidase, which might prevent the entrance of substrate, leading to the decrease of catalytic efficiency of α-glucosidase. Furthermore, glycation assays showed that sinensetin stabilized the structure of bovine serum albumins (BSA), interacted with BSA, strongly inhibited the formation of dityrosine, N′-formylkynurenine and advanced glycation end products (AGEs). This study provided useful information concerning sinensetin preventing and treating type 2 diabetes and its related complications. Sinensetin inhibited α-glucosidase activity and non-enzymatic glycation reaction. Unlabelled Image • Sinensetin bound with α-glucosidase and changed its conformation. • The binding was a spontaneous process primarily driven by hydrophobic interaction. • Sinensetin suppressed glycation-induced protein oxidation. • Sinensetin exhibited strong inhibitory activities on α-glucosidase and glycation. • Sinensetin exerted hypoglycemic activity via multiple targets. [ABSTRACT FROM AUTHOR]