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Review
. 2024 Aug 26;16(17):2856.
doi: 10.3390/nu16172856.

Resveratrol: A Multifaceted Guardian against Anxiety and Stress Disorders-An Overview of Experimental Evidence

Vadim E Tseilikman  1   2   3 , Olga B Tseilikman  1   3 , Oleg N Yegorov  3 , Alina A Brichagina  3 , Marina N Karpenko  4 , David V Tseilikman  3 , Vladislav A Shatilov  1   3 , Maxim S Zhukov  3 , Jurica Novak  5
Affiliations
Review

Resveratrol: A Multifaceted Guardian against Anxiety and Stress Disorders-An Overview of Experimental Evidence

Vadim E Tseilikman et al. Nutrients. .

Abstract

The medicinal properties of resveratrol have garnered increasing attention from researchers. Extensive data have been accumulated on its use in treating cardiovascular diseases, immune system disorders, cancer, neurological diseases, and behavioral disorders. The protective mechanisms of resveratrol, particularly in anxiety-related stress disorders, have been well documented. However, less attention has been given to the side effects of resveratrol. This review explores not only the mechanisms underlying the anxiolytic effects of resveratrol but also the mechanisms that may lead to increased anxiety following resveratrol treatment. Understanding these mechanisms is crucial for enhancing the efficacy of resveratrol in managing anxiety disorders associated with stress and PTSD.

Keywords: PTSD; anxiety; glucorticoids; limbic–hypothalamus–pituitary axis; monoamines; neuroinflammation; resveratrol.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Two-dimensional (A) and 3D (B) representations of resveratrol’s molecular geometry.
Figure 2
Figure 2
Molecular pathways involved in the neuroprotective effects of resveratrol.
Figure 3
Figure 3
Resveratrol impact on metabolism via SIRT1/AMPK/PGK1-α pathway, indicated by upregulation (upward arrows) or downregulation (downward arrows).
Figure 4
Figure 4
Resveratrol upregulates neuroplasticity and downregulates neuroinflammation.
Figure 5
Figure 5
Depiction of the pathogenesis of stress-related anxiety disorders, focusing on neuroinflammation, oxidative stress, mitochondrial dysfunction, and other key factors (A). Illustration of resveratrol’s potential to address these factors, highlighting its therapeutic role in anxiety management (B).
Figure 6
Figure 6
Oxidative stress in the brain is involved in the development of anxiety disorders.
Figure 7
Figure 7
The main molecular pathways supporting the antianxiety effects of resveratrol include the SIRT1/AMPK/CREB pathway: RES reverses the imbalance in neurotransmitters (1); the SIRT1/AMPK/BDNF pathway: RES improves synaptic plasticity (2); the PGK-1α pathway: RES increases the biogenesis of mitochondria (3); and the AMPK/Glut pathway: RES improves glucose uptake by neuronal cells (4).
Figure 8
Figure 8
Resveratrol aggravates anxiety disorder via the SIRT1/NHL2/MAO-A pathway. RES exhibits a dual effect on stress-related anxiety behavior; while it has antianxiogenic properties, it can also mediate proanxiogenic effects through SIRT1 activation. SIRT1 induces the deacetylation of NHLH2 transcriptional factors, leading to increased MAO-A expression and decreased 5-HT concentration in neurons, which enhances anxiety behavior. The miRNAs miR-142, miR-34a, and miR-34c downregulate the proanxiety effect of the SIRT1/NHLH2/MAO-A pathway.
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