Mechanistic Insights into the Inhibitory Activities of Chemical Constituents from the Fruits of Terminalia boivinii on alpha-Glucosidase

Regulation of key digestive enzymes is currently considered an effective remedy for diabetes mellitus. In this study, bioactive constituents were purified from Terminalia boivinii fruits and identified by H-1-NMR, C-13-NMR and El-MS. In vitro and in silico methods were used to evaluate alpha-glucosidase, alpha-amylase, and lipase inhibition activities. Compounds 1, 2, and 4-7 with IC50 values between 89 and 445 mu M showed stronger alpha-glucosidase inhibitory activities than the antihyperglycemic drug acarbose (IC50 = 1463.0 +/- 29.5 mu M). However, the compounds showed lower inhibitory effects against a-amylase and lipase with IC50 values above 500 mu M than acarbose (IC50 = 16.7 +/- 3.5 mu M) and ursolic acid (IC50 = 89.5 +/- 5.6 mu M), respectively. Lineweaver-Burk plots showed that compounds 1, 2, and 7 were non-competitive inhibitors, compounds 4 and 5 were competitive inhibitors and compound 6 was a mixed-type inhibitor. Fluorescence spectroscopic data showed that the compounds altered the microenvironment and conformation of alpha-glucosidase. Computer simulations indicated that the compounds and enzyme interacted primarily through hydrogen bonding. The findings indicated that the compounds were inhibitors of alpha-glucosidase and provided significant structural basis for understanding the binding activity of the compounds with alpha-glucosidase.