Natural triterpenoids isolated from Akebia trifoliata Stem Explants exerts hypoglycemic effect via inhibits α-glucosidase and stimulates glucose uptake in insulin-resistance HepG2 cells.

The inhibition of α-glucosidase activity is a prospective approach to prevent postprandial hyperglycemia in the treatment of type 2 diabetes mellitus. Herein, we investigated the inhibition of three triterpenoid compounds ( 1-3 ) of Akebia trifoliata stem, namely hedragenin, 3-Epiakebonoic acid, and arjunolic acid on α-glucosidases by enzyme kinetics and molecular docking. The results indicated that three triterpenoids exhibited excellent inhibitory activities against α-glucosidase. Compounds ( 1-3 ) showed the strongest inhibition with IC 50 values of 42.1 ± 5.4, 19.6 ± 3.2, and 11.2 ± 2.3 µM, respectively, as compared to the positive control acarbose (IC 50 = 106.3 ± 8.2). The kinetics of enzyme inhibition showed that compounds (1-3) were competitive, mixed, and non-competitive types inhibition against α-glucosidase. The inhibition constants (K i ) value of compounds ( 1-3 ) were calculated to be 21.21, 7.7, and 3.18 μM, respectively. Docking analysis determined the interaction of compounds ( 1-3 ) and α-glucosidase was mainly forced by hydrogen bonds and hydrophobic interaction, which could be effectively inserted into the active pocket of α-glucosidase. On the other hand, insulin resistance HepG2 cells model conducted in this study (10 -7 M insulin administered to the HepG2 cells during 24 h) and the glucose uptake assays showed that test compounds with no cytotoxicity concentrations ranging from 6.25 to 25 μM displayed high activities in promoting the glucose uptake in insulin-resistant HepG2 cells. These triterpenoids exhibited dual therapeutic effects of α-glucosidase inhibition and glucose uptake promotion, thus they could be used as antidiabetic agents for developing novel drugs against type 2 diabetes.