Investigation of the inhibitory activity of triterpenoids isolated from Actinidia polygama stems against /?-glucuronidase via enzyme kinetics, molecular docking, and molecular dynamics analyses

초록

Actinidia polygama, well-known for its traditional medicinal properties, has garnered significant attention due to its distinctive chemical composition. In this study, we isolated and structurally elucidated 11 known compounds, including a monoterpene glycoside ( 1 ), eight triterpenoids ( 2 - 9 ), and two lignan glycosides ( 10 and 11 ), from A. polygama stems. Notably, the inhibitory activity of these compounds on /?- glucuronidase activity was evaluated for the first time. Our results show that 2a,3a,24-trihydroxyurs-12-en-28-oic acid ( 4 ), strongly inhibited /?- glucuronidase (IC 50 = 14.36 +/- 0.42 mu M) to a degree much higher than that of the positive control ( D -saccharic acid 1,4-lactone, DSA; IC 50 = 16.30 +/- 0.21 mu M). Furthermore, the results of an enzyme kinetics analysis indicate that compound 4 acts as a non-competitive inhibitor of /?- glucuronidase. Finally, the findings from molecular docking and molecular dynamics simulations confirmed the inhibition mode of compound 4 , its interaction with the allosteric site of /?- glucuronidase, and the stability of the complex in the bound state.

키워드