Triterpenoids from Kochiae Fructus: Glucose Uptake in 3T3-L1 Adipocytes and a-Glucosidase Inhibition, In Silico Molecular Docking

In this study, three new triterpenes (1-3) and fourteen known triterpenoids (4-17) were isolated from the ethanol extract of Kochiae Fructus, and their structures were elucidated by analyzing UV, IR, HR-ESI-MS, 1D, and 2D NMR spectroscopic data. Among them, compounds 6, 8, and 11-17 were isolated for the first time from this plant. The screening results of the glucose uptake experiment indicated that compound 13 had a potent effect on glucose uptake in 3T3-L1 adipocytes at 20 mu M. Meanwhile, compounds 3, 9 and 13 exhibited significant inhibitory activities against alpha-glucosidase, with IC50 values of 23.50 +/- 3.37, 4.29 +/- 0.52, and 16.99 +/- 2.70 mu M, respectively, and their alpha-glucosidase inhibitory activities were reported for the first time. According to the enzyme kinetics using Lineweaver-Burk and Dixon plots, we found that compounds 3, 9 and 13 were alpha-glucosidase mixed-type inhibitors with K-i values of 56.86 +/- 1.23, 48.88 +/- 0.07 and 13.63 +/- 0.42 mu M, respectively. In silico molecular docking analysis showed that compounds 3 and 13 possessed superior binding capacities with alpha-glucosidase (3A4A AutoDock score: -4.99 and -4.63 kcal/mol). Whereas compound 9 showed +2.74 kcal/mol, which indicated compound 9 exerted the effect of inhibiting alpha-glucosidase activity by preferentially binding to the enzyme-substrate complex. As a result, compounds 3, 9 and 13 could have therapeutic potentials for type 2 diabetes mellitus, due to their potent hypoglycemic activities.

Automated summary

Three new triterpenes and fourteen known triterpenoids were isolated from Kochiae Fructus, and their structures were elucidated. Compound 13 showed potent effect on glucose uptake in adipocytes. Compounds 3, 9, and 13 exhibited significant inhibitory activities against alpha-glucosidase, with their inhibitory activities and binding capacities with alpha-glucosidase reported for the first time. These compounds could have therapeutic potentials for type 2 diabetes mellitus.