Can Resveratrol Influence the Activity of 11β-Hydroxysteroid Dehydrogenase Type 1? A Combined In Silico and In Vivo Study

The enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1) is an NADPH-dependent reductase, responsible for the activation of cortisol by reducing cortisone. Resveratrol (RES), a type of natural polyphenol, is reported to be able to slow the progression of cancer and cardiovascular disease and improve the health of mice on a high-calorie diet. In this article, we applied molecular docking and molecular dynamics simulations to investigate the possibility of binding RES to 11 beta-HSD-1. The 11 beta-HSD-1:RES complex is stable on the mu s time scale, and backbone RMSD-based clustering identified three conformations. Special attention was paid to the interaction pattern between the ligand and the target molecule, revealing hydrogen bonds between the hydroxyl group of RES and Thr124, as well as hydrophobic interactions responsible for the binding. In vivo studies demonstrated the ability of resveratrol at a dose of 40 mg/kg to reduce 11 beta-HSD-1 activity in the liver of rats under conditions of experimental post-traumatic stress disorder (PTSD), as well as in non-stressed animals. In both cases, the resveratrol-induced reduction in 11 beta-HSD-1 activity was accompanied by an increase in plasma corticosterone levels and a decrease in anxiety levels in the plus maze test.

Automated summary

This study investigated the binding possibility of resveratrol to 11 beta-HSD-1 using molecular docking and molecular dynamics simulations. The results showed that the 11 beta-HSD-1:resveratrol complex was stable on the microsecond time scale, and binding was achieved through hydrogen bonds and hydrophobic interactions. In vivo studies demonstrated the ability of resveratrol to reduce 11 beta-HSD-1 activity in the liver, accompanied by changes in corticosterone levels and anxiety levels.