Inhibitory kinetics and mechanism of oleanolic acid on α-glucosidase

Inhibition of alpha-glucosidase is considered as an effective approach to treat type 2 diabetes. Therefore, it is of great significance to study the inhibition of this enzyme. In the present study, the inhibitory activity of oleanolic acid (OA) on alpha-glucosidase and their interaction mechanism were investigated. The inhibition kinetic analysis showed that OA reversibly inhibited alpha-glucosidase activity in a mixed-type manner with an IC50 value of 3.04 +/- 0.05 mu M, and the inhibition followed a multi-phase kinetic process with a first-order reaction. The change of enthalpy and entropy indicated that the binding of OA to glucosidase was mainly driven by hydrophobic interaction and hydrogen bonding, and the binding distance was estimated at 3.51 nm. Synchronous fluorescence, circular dichroism (CD) and Fourier transform infrared spectra (FT-IR) showed that the binding of OA to alpha-glucosidase induced rearrangement and conformational changes of the enzymes. The molecular docking illustrated that OA entered the active center of alpha-glucosidase and interacted with the amino acid residues Asp-352 and ultimately inhibiting the enzyme activity.

Automated summary

The study demonstrated that oleanolic acid inhibits alpha-glucosidase activity in a reversible mixed-type manner driven mainly by hydrophobic interaction and hydrogen bonding. The binding of OA induced conformational changes in the enzyme and ultimately inhibited its activity by interacting with specific amino acid residues in the active center.