Can Resveratrol Influence the Activity of 11ß-Hydroxysteroid Dehydrogenase Type 1? A Combined In Silico and In Vivo Study.
Pharmaceuticals (Basel)
; 16(2)2023 Feb 07.
Article
en En
| MEDLINE
| ID: mdl-37259398
The enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11ß-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 11ß-HSD-1. The 11ß-HSD-1:RES complex is stable on the µs 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 11ß-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 11ß-HSD-1 activity was accompanied by an increase in plasma corticosterone levels and a decrease in anxiety levels in the plus maze test.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Pharmaceuticals (Basel)
Año:
2023
Tipo del documento:
Article
País de afiliación:
Croacia
Pais de publicación:
Suiza