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

• Published in: International journal of molecular sciences 2023-01, Vol.24 (3), p.2454
• Main Authors: Chen, Xue-Lin, Zhang, Kun, Zhao, Xia, Wang, Han-Lei, Han, Mei, Li, Ru, Zhang, Zhen-Nan, Zhang, Yu-Mei
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocytes; Adipocytes - metabolism; alpha-Glucosidases - metabolism; Animals; Antifungal agents; Binding; Carbohydrates; Carbon; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Enzymes; Glucose; Glucosidase; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Hypoglycemic Agents - chemistry; Insulin resistance; Metabolism; Mice; Molecular docking; Molecular Docking Simulation; Molecular Structure; NMR; Nuclear magnetic resonance; Triterpenes; Triterpenes - pharmacology; Triterpenoids; α-Glucosidase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24032454

In this study, three new triterpenes ( - ) and fourteen known triterpenoids ( - ) 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 , , and - were isolated for the first time from this plant. The screening results of the glucose uptake experiment indicated that compound had a potent effect on glucose uptake in 3T3-L1 adipocytes at 20 μM. Meanwhile, compounds , and exhibited significant inhibitory activities against -glucosidase, with IC values of 23.50 ± 3.37, 4.29 ± 0.52, and 16.99 ± 2.70 µM, respectively, and their -glucosidase inhibitory activities were reported for the first time. According to the enzyme kinetics using Lineweaver-Burk and Dixon plots, we found that compounds , and were -glucosidase mixed-type inhibitors with values of 56.86 ± 1.23, 48.88 ± 0.07 and 13.63 ± 0.42 μM, respectively. In silico molecular docking analysis showed that compounds and possessed superior binding capacities with -glucosidase (3A4A AutoDock score: -4.99 and -4.63 kcal/mol). Whereas compound showed +2.74 kcal/mol, which indicated compound exerted the effect of inhibiting -glucosidase activity by preferentially binding to the enzyme-substrate complex. As a result, compounds , and could have therapeutic potentials for type 2 diabetes mellitus, due to their potent hypoglycemic activities.