Resveratrol and Depression in Animal Models: A Systematic Review of the Biological Mechanisms

Abstract

Depression is currently treated by pharmacotherapies that can elicit debilitating side effects for patients. Novel treatment options with limited side effects are currently being researched. Resveratrol is a polyphenol and phytoalexin found in the skins of grapes, red wine, Japanese knotweed, and peanuts. It has been studied extensively for its antioxidant and anti-inflammatory properties. Resveratrol has also gained attention for its neuroprotective properties. The aim of the review was to examine the mechanisms by which resveratrol reduces depressive behaviors in animal models. In total, 22 studies met the established criteria for final review. Behavioral aspects of depression were investigated using validated measures such as the forced swimming test, tail suspension test, sucrose preference test, and open field test. While many physical measures were taken, three main biological mechanisms were explored: Regulation of the hypothalamic–pituitary–adrenal axis; decreased inflammation; and increased Brain-Derived Neurotrophic Factor and neurogenesis. Based on these findings, resveratrol may be deemed an effective treatment for depression in animal models at doses between 10–80 mg/kg/day, although higher doses had the most significant effects. Future studies should examine the effects of resveratrol on depression in humans to determine the eligibility of resveratrol as a natural antidepressant with less severe side effects.

Health benefits of resveratrol administration

“…Similarly, the observed beneficial effect of resveratrol on hyperalgesia in rats with chronic neuropathic pain is due to the inhibition of the expression of glial fibrillary acidic protein and the P2X7 receptor, a key player in nervous pathological pain (Xie et al, 2017). In addition, resveratrol at the dose of 10-80 mg/kg per day may be an effective treatment for depression in animal models (Moore et al, 2018). There is also evidence that the neuroprotective effect is also enhanced by the antioxidant and anti-inflammatory properties of resveratrol.…”

The Emerging Role of SGK1 (Serum- and Glucocorticoid-Regulated Kinase 1) in Major Depressive Disorder: Hypothesis and Mechanisms

“…Recently, Moore A. et al reviewed a fair amount of evidence showing that resveratrol, a polyphenol with antioxidant and anti-inflammatory properties that highly present in grape skins and therefore in red wine, abrogates depressive-like behavior and neuroinflammatory response, and enhances hippocampal neurogenesis in several animal model of depression. The neuroprotective effects exerted by resveratrol administration (10-80 mg/Kg/die) mainly arise from the enhancing of CREB/BDNF signaling as well as the regulation of HPA axis function (Moore et al, 2018). In addition, resveratrol has also been shown to have an in vitro inhibitory activity on SGK1 in HUH7 human hepatoma cells (Catalogna et al, 2019).…”

Medicinal Herbs and Phytochemicals Used in the Treatment of Depression: A Review

“…Resveratrol has an outstanding property of neuroprotective [82,83]. The resveratrol has a significant effect on the regulation of antioxidant effect by ameliorating the hyperactivity of the HPA axis, and resveratrol is also testified for the metabolism of the noradrenaline and serotonin and acts as another antidepressant.…”