TY - JOUR

T1 - Unraveling the Liver–Brain Axis: Resveratrol’s Modulation of Key Enzymes in Stress-Related Anxiety

AU - Tseilikman, Vadim E.

AU - Tseilikman, Olga B.

AU - Shevyrin, Vadim A.

AU - Yegorov, Oleg N.

AU - Epitashvili, Alexandr A.

AU - Aristov, Maxim R.

AU - Karpenko, Marina N.

AU - Lipatov, Ilya A.

AU - Pashkov, Anton A.

AU - Shamshurin, Maxim V.

AU - Buksha, Irina A.

AU - Shonina, Anna K.

AU - Kolesnikova, Alexandra

AU - Shatilov, Vladislav A.

AU - Zhukov, Maxim S.

AU - Novak, Jurica

PY - 2024/9

Y1 - 2024/9

N2 - Stress-related anxiety disorders and anxiety-like behavior in post-traumatic stress disorder (PTSD) are associated with altered neurocircuitry pathways, neurotransmitter systems, and the activities of monoamine and glucocorticoid-metabolizing enzymes. Resveratrol, a natural polyphenol, is recognized for its antioxidant, anti-inflammatory, and antipsychiatric properties. Previous studies suggest that resveratrol reduces anxiety-like behavior in animal PTSD models by downregulating key enzymes such as 11 (Formula presented.) -hydroxysteroid dehydrogenase type 1 (11 (Formula presented.) -HSD-1) and monoamine oxidases (MAOs). However, the underlying mechanisms remain unclear. In this study, we explored the efficacy of resveratrol in treating stress-induced anxiety using a chronic predator stress model in rats. Resveratrol was administered intraperitoneally at 100 mg/kg following a 10-day stress exposure, and anxiety behavior was assessed with an elevated plus maze. Our results indicated that stress-related anxiety correlated with increased activities of brain MAO-A, MAO-B, and hepatic 11 (Formula presented.) -HSD-1, alongside elevated oxidative stress markers in the brain and liver. Resveratrol treatment improved anxiety behavior and decreased enzyme activities, oxidative stress, and hepatic damage. We demonstrate that resveratrol exerts antianxiogenic effects by modulating glucocorticoid and monoamine metabolism in the brain and liver. These findings suggest resveratrol’s potential as a therapeutic agent for anxiety disorders, warranting further clinical investigation.

AB - Stress-related anxiety disorders and anxiety-like behavior in post-traumatic stress disorder (PTSD) are associated with altered neurocircuitry pathways, neurotransmitter systems, and the activities of monoamine and glucocorticoid-metabolizing enzymes. Resveratrol, a natural polyphenol, is recognized for its antioxidant, anti-inflammatory, and antipsychiatric properties. Previous studies suggest that resveratrol reduces anxiety-like behavior in animal PTSD models by downregulating key enzymes such as 11 (Formula presented.) -hydroxysteroid dehydrogenase type 1 (11 (Formula presented.) -HSD-1) and monoamine oxidases (MAOs). However, the underlying mechanisms remain unclear. In this study, we explored the efficacy of resveratrol in treating stress-induced anxiety using a chronic predator stress model in rats. Resveratrol was administered intraperitoneally at 100 mg/kg following a 10-day stress exposure, and anxiety behavior was assessed with an elevated plus maze. Our results indicated that stress-related anxiety correlated with increased activities of brain MAO-A, MAO-B, and hepatic 11 (Formula presented.) -HSD-1, alongside elevated oxidative stress markers in the brain and liver. Resveratrol treatment improved anxiety behavior and decreased enzyme activities, oxidative stress, and hepatic damage. We demonstrate that resveratrol exerts antianxiogenic effects by modulating glucocorticoid and monoamine metabolism in the brain and liver. These findings suggest resveratrol’s potential as a therapeutic agent for anxiety disorders, warranting further clinical investigation.

UR - https://www.mendeley.com/catalogue/b66f72d6-4028-3d9d-8c07-bcfd6ef90d90/

U2 - 10.3390/biomedicines12092063

DO - 10.3390/biomedicines12092063

M3 - Article

C2 - 39335576

VL - 12

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 9

M1 - 2063

ER -