Inhibitory mechanism of chrysin and diosmetin to α-glucosidase: insights from kinetics, multispectroscopy and molecular docking investigations

Inhibition of alpha-glucosidase activity is a promising method to prevent postprandial hyperglycemia. The inhibitory effect and interaction of chrysin and diosmetin on alpha-glucosidase were studied in this study. The results of inhibition kinetics showed that chrysin and diosmetin reversibly inhibited alpha-glucosidase activity with IC50 value of 26.445 +/- 1.406 mu mol L-1 and 18.380 +/- 1.264 mu mol L-1, respectively. Further research revealed that chrysin exhibited a mixed-type inhibitory pattern against alpha-glucosidase, while diosmetin was noncompetitive inhibitory with Ki value of (2.6 +/- 0.04) x10(-4 )mol L-1. Fluorescence spectroscopy showed that both chrysin and diosmetin could quench the intrinsic fluorescence of alpha-glucosidase, the maximum emission wavelength of tyrosine (Tyr) and tryptophan (Trp) were not moved by chrysin, but red shifted by diosmetin. UV-Vis, fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) measurements showed that the secondary structure and microenvironment of alpha-glucosidase were changed by chrysin and diosmetin. Further analysis of molecular docking showed that chrysin and diosmetin could bind with alpha-glucosidase and might cause the decrease of alpha-glucosidase activity. The results of molecular dynamics (MD) simulation showed that the stability of chrysin (or diosmetin)-alpha-glucosidase complex system was changed during binding process. In conclusion, chrysin and diosmetin are good alpha-glucosidase inhibitors.