Insights into an α-Glucosidase Inhibitory Profile of 4,4-Dimethylsterols by Multispectral Techniques and Molecular Docking.

Inhibition of α-glucosidase activity is closely related to the treatment of type 2 diabetes. However, the potential mechanism by which 4,4-dimethylsterols inhibit α-glucosidase has not been elucidated. In this work, the inhibitory activity and mechanism of 4,4-dimethylsterols against α-glucosidase were studied through kinetic analysis, fluorescence spectroscopy, ultraviolet spectroscopy, circular dichroism, and molecular docking. 4,4-Dimethylsterols showed higher inhibition activity against α-glucosidase than acarbose with an IC 50 value of 0.71 mg/mL and a noncompetitive inhibition type. They could bind to α-glucosidase through van der Waals forces and hydrogen bonds and quench its endofluorescence with a static quenching mechanism. Changes in the secondary structure of α-glucosidase were induced by its binding interaction with 4,4-dimethylsterols. Molecular docking further indicated that a hydrogen bond was generated between OH at the C-3 position of 4,4-dimethylsterols and the α-glucosidase residue Arg-442. This study provides new insights into the potential utilization of 4,4-dimethylsterols as antidiabetic phytochemicals in dietary supplements.