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

Author:

Novak Jurica12ORCID,Tseilikman Vadim E.3,Tseilikman Olga B.34,Lazuko Svetlana S.5,Belyeva Lyudmila E.6,Rahmani Azam7,Fedotova Julia8ORCID

Affiliation:

1. Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia

2. Center for Artificial Intelligence and Cyber Security, University of Rijeka, 51000 Rijeka, Croatia

3. Scientific and Educational Center ‘Biomedical Technologies’, School of Medical Biology, South Ural State University, 454080 Chelyabinsk, Russia

4. Faculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, Russia

5. Department of Physiology, Vitebsk State Medical University, Frunze Av. 27, 210023 Vitebsk, Belarus

6. Department of Pathophysiology, Vitebsk State Medical University, Frunze Av. 27, 210023 Vitebsk, Belarus

7. Nursing and Midwifery Care Research Center, School of Nursing and Midwifery, Tehran University of Medical Sciences, Tehran P.O. Box 14665-354, Iran

8. Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology RAS, 6 Emb. Makarova, 199034 Saint Petersburg, Russia

Abstract

The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-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 11β-HSD-1. The 11β-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 11β-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 11β-HSD-1 activity was accompanied by an increase in plasma corticosterone levels and a decrease in anxiety levels in the plus maze test.

Funder

Priority-2030

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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