Written by Johannes Haerle, PhD, Senior Technical Manager, Evolva
Scientists from the University of Buffalo investigated resveratrol and how this polyphenol helps combat depression and anxiety. The underlying mechanism discovered in this preclinical trial is described as resveratrol’s ability to inhibit the enzyme phosphodiesterase, which controls the cellular signaling molecule cAMP. This mechanism has been put into the spotlight due to its ability to also regulate energy creation and support physical stamina.
Indeed, depression and anxiety may be related to energy and physical stamina, analogous to the Latin phrase “Mens sana in corpore sano” which originates back to the Roman poet Juvenal, meaning “a healthy mind in a healthy body.” In fact, if the perception of mood and wellbeing expressed by anxiety and depression can be linked to energy and physical stamina, a strong immune system might be the major determinant or even prerequisite. Therefore, we thought a review of resveratrol’s beneficial impact on the immune system, mood and wellbeing may serve as an interesting backdrop to this latest research on resveratrol’s role for healthy living.
Resveratrol protects against environmental stress
Resveratrol is produced naturally in grapes and other plants to protect itself against UV radiation, environmental stress and fungal infections 1. Due to the anti-inflammatory and vasoactive properties, resveratrol received early attention especially in traditional Chinese and Japanese medicine. Today, resveratrol accounts for more than 12,000 scientific studies and 170+ human clinical trials, making it one of the most studied active ingredients within the dietary supplement industry. A number of beneficial health effects can be attributed to resveratrol, with researchers and clinicians pointing to the efficacy and effectivity of resveratrol based on its molecular, cellular and systemic interactions.2,3
Poor nutrition and physical inactivity can be a drawback of the Western lifestyle, and metabolic oxidative stress and systemic inflammation can be one of the consequences of it. This may challenge the immune system and if left unchecked, can result in fatigue and common colds and thereby lead to chronic diseases that may impair heart and brain health.4
Balanced nutrition and physical exercise are essential to healthy living, and certain nutraceuticals and functional ingredients like resveratrol are known to scavenge oxidative stress, reduce inflammation and help support a strong immune system.5 In combination with a balanced lifestyle, resveratrol helps maintain a healthy immune system in a multifaceted approach.
First, on the molecular level, resveratrol blocks an enzyme that causes the behavior of anxiety and depression by inhibiting the reduction of the cellular mediator called cAMP; this was recently highlighted in the University of Buffalo preclinical study. 6 Further downstream of the signaling cascade, cAMP also supports the increase of NAD+ and the activity of Sirt1; it is these two intermediaries plus the activation of AMPK, an essential energy sensor in cells, by which resveratrol can improve the mitochondrial function, energy creation and physical stamina.7
Resveratrol has also been identified to modulate the activity of NF-κB, which exhibits a key role in activating pro-inflammatory mediators. This activity can inhibit the release of destructive immune reactions and thereby help balance healthy immune responses.8,9 Furthermore, resveratrol has been shown to inhibit the enzyme cyclooxygenase (COX), which may help alleviate symptoms like inflammation and pain.10,11 In fact, resveratrol has been shown in human clinical trials to reduce pain and fatigue and boost the perception of well-being.12
On the cellular level, resveratrol has significant effects on the lifecycle of immune cells.3 Presented in a preclinical study, resveratrol regulates the humoral immune responses by upregulating the release of interferon gamma (IFN-𝛾), which acts as an immuno-stimulant and downregulates the release of tumor necrosis factor (TNF-𝛼) which is a main trigger causing inflammation and also fever.13
Documented in a human clinical trial, resveratrol was tested on several biomarkers of oxidative stress and then compared to a placebo group. This trial indicated that resveratrol reduced the plasma protein carbonyl content, which is a widely utilized measure of protein oxidation, and significantly increased the plasma total antioxidant capacity. Furthermore, resveratrol consumption increased the endogenous regulator (Nrf2) that regulates the activity of antioxidant proteins which protects against oxidative damage (e.g. the enzyme super oxide dismutase (SOD)).14
On the systemic level and documented in human clinical trials, resveratrol has an overall suppressive effect on oxidative and inflammatory stress, the main cause of a compromised immune system.15 This is a recent conclusion from a meta-analysis study and on 29 selected trials that resveratrol has been recognized as having a beneficial impact on the immune system through regulating key inflammation modulators.16
Antiviral and anti-cold activity of resveratrol
Resveratrol exerts antiviral effects against different DNA and RNA viruses, such as the influenza A virus.17 Resveratrol has also been shown to inhibit the rhinoviruses (HRV), the main cause of common colds, and the symptoms released by inflammatory mediators like cytokine and chemokine molecules in the nasal epithelia. Interestingly, no vaccine or antiviral agents are available yet for the prevention or treatment of HRV mediated respiratory diseases.18
Antibacterial and antifungal activity of resveratrol
Resveratrol selectively exhibits potent antimicrobial activity on human pathogenic bacteria like the MRSA Staphylococcus aureus, the main trigger of difficult-to-treat infections in humans, and also Enterococcus faecalis which can cause life-threatening infections found particularly in hospitals.19 Furthermore, resveratrol also displays potent antifungal activity against human pathogenic fungi Candida albicans, which is the most prevalent cause of fungal infections in humans.20 It should be noted that such antibacterial and antifungal activity supports our immune system in combating unwanted stressors.
Resveratrol helps prevent respiratory challenges
Not only do respiratory infections constitute a social problem, they also have an economic impact and are a burden for families and the workplace. Nutraceuticals like resveratrol can help reduce nasal symptoms and may even help prevent respiratory infections.21 One such study showed that resveratrol supplementation in children revealed a reduction in the number of days with nasal obstruction, rhinorrhea, sneezing, cough, fever, medication use, medical visits, and overall days of school absence.22
We at Evolva are excited to see how resveratrol can support the immune system and beneficially impact overall health and wellbeing. Based on these findings, Evolva continues to actively support human clinical trials to investigate more of such promising health benefits. Please see our webpage https://veriteresveratrol.com and feel free to contact us for further information.
Please note this review is for educational purposes and intended for commercial use only.
- Adrian, M., Jeandet, P., Tesson, L. & Bessis, R. Stilbene Content of Mature Vitis vinifera Berries in Response to UV-C Elicitation. J. Agric. Food Chem. 48, 6103–6105 (2000).
- Koushki, M., Amiri-Dashatan, N., Ahmadi, N., Abbaszadeh, H. A. & Rezaei-Tavirani, M. Resveratrol: A miraculous natural compound for diseases treatment. Food Sci. Nutr. 2473–2490 (2018). doi:10.1002/fsn3.855
- Malaguarnera, L. Influence of Resveratrol on the Immune Response. Nutrients 11, 1–24 (2019).
- Bodai BI, Nakata TE, Wong WT, Clark DR, Lawenda S, Tsou C, Liu R, Shiue L, Cooper N, Rehbein M, Ha BP, Mckeirnan A, Misquitta R, Vij P, Klonecke A, Mejia CS, Dionysian E, Hashmi S, Greger M, Stoll S, C. T. Lifestyle Medicine : A Brief Review of Its Dramatic Impact on Health and Survival. Perm J. 22, 17–25 (2018).
- de Sá Coutinho, D., Pacheco, M. T., Frozza, R. L. & Bernardi, A. Anti-inflammatory effects of resveratrol: Mechanistic insights. Int. J. Mol. Sci. 19, (2018).
- Zhu, X. et al. The antidepressant- and anxiolytic-like effects of resveratrol: involvement of phosphodiesterase-4D inhibition. (Elsevier Ltd, 2019). doi:10.1016/j.neuropharm.2019.04.022
- Park, S. J. et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148, 421–433 (2012).
- Manna, S. K., Mukhopadhyay, A. & Bharat, B. Resveratrol Suppresses TNF-Induced Activation of Nuclear Transcription Factors NF-KB, Activator Protein-1, and Apoptosis: Potential Role of Reactive Oxygen Intermediates and Lipid Peroxidation. J Immunol 164, 6509–6519 (2000).
- Li, Q. & Verma, I. M. NF- κB REGULATION IN THE IMMUNE SYSTEM. Nat. Rev. Immunol. 2, 725–734 (2002).
- Szewczuk, L. M., Forti, L., Stivala, L. A. & Penning, T. M. Resveratrol is a Peroxidase-mediated Inactivator of COX-1 but Not COX-2. J. Biol. Chem. 279, 22727–22737 (2004).
- Subbaramaiah, K. et al. Resveratrol Inhibits Cyclooxygenase-2 Transcription and Activity in Phorbol Ester-treated Human Mammary Epithelial Cells. J. Biol. Chem. 273, 21875–21882 (1998).
- Wong, R. H. X., Evans, H. M. & Howe, P. R. C. Resveratrol supplementation reduces pain experience by postmenopausal women. Menopause 24, 916–922 (2017).
- Fu, Q. et al. Effect of Resveratrol Dry Suspension on Immune Function of Piglets. Evidence-based Complement. Altern. Med. 2018, (2018).
- Seyyedebrahimi, S., Khodabandehloo, H., Nasli Esfahani, E. & Meshkani, R. The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial. Acta Diabetol. (2018). doi:10.1007/s00592-017-1098-3
- Ghanim, H. et al. An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J. Clin. Endocrinol. Metab. 95, 1–8 (2010).
- Hajizadeh-sharafabad, F. & Sahebkar, A. The impact of resveratrol on toxicity and related complications of advanced glycation end products : A systematic review. 1–15 (2019). doi:10.1002/biof.1531
- Palamara, A. T. et al. Inhibition of Influenza A Virus Replication by Resveratrol. JID 191, 1719–29 (2005).
- Mastromarino, P. et al. Resveratrol inhibits rhinovirus replication and expression of inflammatory mediators in nasal epithelia. Antiviral Res. (2015). doi:10.1016/j.antiviral.2015.08.010
- Paulo, L., Ferreira, S., Gallardo, E., Queiroz, J. A. & Domingues, F. Antimicrobial activity and effects of resveratrol on human pathogenic bacteria. World J. Microbiol. Biotechnol. 26, 1533–1538 (2010).
- Jung, H. J. et al. Fungicidal effect of resveratrol on human infectious fungi. Arch. Pharm. Res. 28, 557–560 (2005).
- Miraglia Del Giudice, M. et al. Resveratrol plus carboxymethyl-β-glucan reduces nasal symptoms in children with pollen-induced allergic rhinitis. Curr. Med. Res. Opin. 30, 1931–1935 (2014).
- Varricchio, A. M. et al. Resveratrol plus carboxymethyl-beta-glucan in children with recurrent respiratory infections: a preliminary and real-life experience. Ital. J. Pediatr. 40, 93 (2014).