Resveratrol is a natural non-flavonoid polyphenol found abundantly in the skins and seeds of berries and grapes and, of course, in red wine, which has numerous pharmacological properties including antioxidant, anti-stress and antidepressant-like abilities. A recent study published in Experimental and Therapeutic Medicine last April by a scientist team from Xinxiang Medical University, also explored the therapeutic effects of resveratrol on mice with depression. They selected lab rats with an induced depression and divided them into groups: the model group, the low dose, the medium dose, the high dose group and the control group. 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 placebo. 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 concluded that 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.
The new 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 study was co-authored by Xiaoxing Yin, PhD, professor of Pharmacology at Xuzhou Medical University in China. According to scientists, resveratrol may be an effective alternative to drugs for treating patients suffering from depression and anxiety disorders. This compound specifically played a role in the enzyme phosphodiesterase 4 (PDE4) which in turn is influenced by the stress hormone corticosterone. Hormones 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 final concentration of corticosterone, they could induce isoforms of PDE in the mice brain called PDE2A, PDE3B, PDE4A, PDE4D, PDE10 and PDE11. These were seen in the HT-22 cell lab model, 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 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, most likely acting on signaling mechamisms that the Authors did not delve in. The researchers concluded that resveratrol-induced antidepressant- and anxiolytic-like effects are mediated by PDE4D enzyme. 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 behaviors. 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 as alcohol consumption is associated with various health risks. 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. Therefore, finding stable and effective (if natural even better) molecular options for these medical conditions, may represent a viable avenue of natural treatment.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Zhu X et al. Neuropharmacology 2019 Jul 15;153:20-31.
Wang G et al. Oncotarget 2016 Apr 5; 7(14):17380-392.
Zhao P et al. Biochim Biophys Acta 2013; 1834(10):2089.