Resveratrol shows promise for anxiety and depression

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A new study has shown that the compound resveratrol found in red wine demonstrates stress relieving effects in anxiety and depression. This could be due to resveratrol’s ability to control an enzyme in the brain that is liked to stress say the researchers from the University at Buffalo in collaboration with Xuzhou Medical University in China.

Image Credit: Ievgenii Meyer / Shutterstock
Image Credit: Ievgenii Meyer / Shutterstock

The study titled, “The antidepressant- and anxiolytic-like effects of resveratrol: Involvement of phosphodiesterase-4D inhibition” was published in the latest issue of the journal Neuropharmacology.

The Anxiety and Depression Association of America says that nearly 16 and 40 million people respectively in the United States suffer from depression and anxiety. Ying Xu, co-lead author and research associate professor in the UB School of Pharmacy and Pharmaceutical Sciences said in a statement, “Resveratrol may be an effective alternative to drugs for treating patients suffering from depression and anxiety disorders.”

The study was co-authored by Xiaoxing Yin, PhD, professor at Xuzhou Medical University in China.

The team explained that resveratrol has been shown to numerous beneficial properties on health and is found abundantly in the skins and seeds of berries and grapes. The team explained that resveratrol is a “natural non-flavonoid polyphenol found in red wine, which has numerous pharmacological properties including anti-stress and antidepressant-like abilities.” They noted that this compound specifically played a role in the enzyme phosphodiesterase 4 (PDE4) which in turn is influenced by the stress hormone corticosterone. This was a finding that has been novel to their study, say the researchers.

The team explains that cortisol or corticosterone is released in the body as a response to stress and excess stress can trigger excess release of the hormone that reaches the brain and leads to depression and anxiety. At present the treatment for depression and anxiety focuses on serotonin or noradrenaline – neurotransmitters in the brain. Xu said that one in three patients with depression and/or anxiety disorders benefit from the drug modulating the neurotransmitters and reach full remission.

For their study the team used lab mice on which they showed that PDE4 in the brain was influenced by the excess cortisol released as a response to stress. This led to anxiety and depression related symptoms in the mice. They explain the PDE4 is capable of lowering the cyclic adenosine monophosphate or cAMP in the brain which is a messenger that causes signalling of several physiological processes including cell division, movement and death within the body. Alteration of the PDE4 and cAMP in the brain led to alterations in the structure of the brain, they noted.

The team investigated both in vivo and in vitro effects of resveratrol on the lab mice. They noted that a specific region of the brain called the hippocampus was altered by the increase in the PDE4 expression that led to the anxiety and depression like behaviour in the mice. They noted that using only “100 μM” or miniscule amounts of corticosterone, they could induce subtypes of PDE4 in the mice brain called, “PDE2A, PDE3B, PDE4A, PDE4D, PDE10 and PDE11”. These were seen in the “HT-22 cells,” in the lab and led to significant cell damage. When treated with resveratrol the cells became more viable and with rising dose of the compound the cell viability rose, the researchers explained. PDE4D expression was specifically affected by resveratrol the team wrote.

The team found that the compound resveratrol could help reverse these effects and showed a neuroprotective effect in the brain by working against the damage caused by corticosterone. The compound successfully inhibited the expression of PDE4. The researchers concluded, “resveratrol-induced antidepressant- and anxiolytic-like effects are mediated by PDE4D. Overall, these findings support the hypothesis that PDE4D-mediated cAMP signaling plays an important role in resveratrol's protective effects on stress-induced depression- and anxiety-like behavior.” The team is hopeful that this study could mean novel therapeutic approached to depression and anxiety using resveratrol.

They add in warning that resveratrol’s beneficial effect does not translate to the red wine consumption and alcohol consumption is associated with various health risks.

Related study

A recent study (published in Experimental and Therapeutic Medicine in April 2019), also explored the therapeutic effects of resveratrol on mice with depression. The study was titled, “Therapeutic effect of resveratrol on mice with depression” from authors Zheng Gu and colleagues from Xinxiang Medical University.

They selected lab rats with an induced depression and divided them into groups, “the model group, the low dose group, the medium dose group and the high dose group” and the control group. The team writes that the rats in the low, medium and high dose groups were given injections of resveratrol 10, 20 and 30 mg/kg, respectively. The control and model groups received normal saline. After a treatment for 21 days tests revealed reduction in depression and brain tests showed that there was a rise in brain dopamine and serotonin level – the indicators of depression. There was also a significant rise in Neuropeptide Y expression in the brain in rats treated with resveratrol.

The team wrote in conclusion, “Resveratrol can significantly increase the levels of neurotransmitters DA and 5-HT in the prefrontal cortex and increase the expression of NPY in the brain, which can play an antagonistic role in depression.”

Journal reference:

The antidepressant- and anxiolytic-like effects of resveratrol: Involvement of phosphodiesterase-4D inhibition, Neuropharmacology, Volume 153, 15 July 2019, Pages 20-31, Xia Zhu, Wenhua Li, Yongkun Li, Wenhua Xu, Yirong Yuan, Victor Zheng, Hanting Zhang, James M. O'Donnell, Ying Xu, Xiaoxing Yin,

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.


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