New Insights into the Inhibition Mechanism of Betulinic Acid on α‑Glucosidase

Betulinic acid (BA), an important pentacyclic triterpene widely distributed in many foods, possesses high antidiabetic activity. In this study, BA was found to exhibit stronger inhibition of α-glucosidase than acarbose with an IC50 value of (1.06 ± 0.02) × 10–5 mol L–1 in a mixed-type manner. BA bound with α-glucosidase to form a BA−α-glucosidase complex, resulting in a more compact structure of the enzyme. The obtained concentrations and spectra profiles of the components resolved by the multivariate-curve resolution–alternating least-squares confirmed the formation of the BA−α-glucosidase complex. Molecular docking showed that BA tightly bound to the active cavity of α-glucosidase, which might hinder the entrance of the substrate leading to a decline in enzyme activity. The chemical modification of α-glucosidase verified the results of the computer simulation that the order of importance of the four amino acid residues in the binding process was His > Tyr > Lys > Arg.