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

Inhibition of alpha-glucosidase activity is closely related to the treatment of type 2 diabetes. However, the potential mechanism by which 4,4-dimethylsterols inhibit alpha-glucosidase has not been elucidated. In this work, the inhibitory activity and mechanism of 4,4-dimethylsterols against alpha-glucosidase were studied through kinetic analysis, fluorescence spectroscopy, ultraviolet spectroscopy, circular dichroism, and molecular docking. 4,4-Dimethylsterols showed higher inhibition activity against alpha-glucosidase than acarbose with an IC50 value of 0.71 mg/mL and a noncompetitive inhibition type. They could bind to alpha-glucosidase through van der Waals forces and hydrogen bonds and quench its endofluorescence with a static quenching mechanism. Changes in the secondary structure of alpha-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 alpha-glucosidase residue Arg-442. This study provides new insights into the potential utilization of 4,4-dimethylsterols as antidiabetic phytochemicals in dietary supplements.