Inhibitory kinetics and mechanism of oleanolic acid on α-glucosidase

Inhibition of α-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 α-glucosidase and their interaction mechanism were investigated. The inhibition kinetic analysis showed that OA reversibly inhibited α-glucosidase activity in a mixed-type manner with an IC50 value of 3.04 ± 0.05 µM, 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 α-glucosidase induced rearrangement and conformational changes of the enzymes. The molecular docking illustrated that OA entered the active center of α-glucosidase and interacted with the amino acid residues Asp-352 and ultimately inhibiting the enzyme activity.