Exploring Resveratrol’s Potential to Activate NRF2 Signaling
Resveratrol is an antioxidant found naturally in foods like grapes, peanuts, and red wine. Some exciting new research shows it may help activate NRF2 – a protein that controls our cells’ natural defense systems.
NRF2 is like a supervisor for our cells’ crew of antioxidant and detox proteins. When NRF2 gets called into action, it kicks those healthy proteins into high gear to fend off damage from oxidative stress, inflammation, and other bad actors.
Here’s where resveratrol comes in – studies suggest it can actually boost NRF2 activity by changing the epigenetic controls on the NRF2 gene. Epigenetics basically means how genes get turned on and off through chemical tags and markers. Resveratrol seems able to remove silencing markers on NRF2, letting it spring into action.
Research on liver and breast cells showed that in high glucose environments, NRF2 tended to become methylated and muted. But resveratrol reversed that effect, up-regulating both NRF2 and its antioxidant defenses. It accomplishes this by inhibiting enzymes that methylate DNA. So in essence, resveratrol is demethylating and unlocking the NRF2 code.
Through these epigenetic impacts, studies found resveratrol could lower oxidative stress and damping down inflammation in cells and animals. One study also saw resveratrol up-regulate NRF2 and suppress mammary tumor growth in a rat model of breast cancer.
The science is still emerging, but it appears this humble natural compound can influence NRF2 at the genetic level – strengthening our cells’ own antioxidant systems from the inside out. More research is needed to confirm if resveratrol works the same way in humans. But the current evidence gives us a tantalizing clue that resveratrol may offer whole body benefits by tapping into our cells’ innate wellness defenses. Pretty cool how nature packs so much power in foods like red wine and blueberries!
But wait there’s more!
Interestingly there is research that points to (uncontrolled) NRF2 upregulation being problematic for tumor growth.
it is also becoming widely recognised that permanent hyper-activation of NRF2 resulting from somatic mutations in the gene that encodes NRF2, or in genes associated with its degradation, is frequently observed in certain cancers and associated with poor outcome.
(Robertson 2020)
Nevertheless, there is strong evidence to show Resveratrol continues to have a useful role in Cancer. For more on Resveratrol and Cancer see Epithelial-Mesenchymal Transition (EMT), Skin, Cellular Signaling, and Resveratrol
Given this nuanced situation, is it possible we are looking at the possibility that resveratrol may act as a NRF2 modulator rather than simple activator?
It appears that Resveratrol activates NRF2 in healthy cells transiently, while also inhibiting pathways that lead to uncontrolled NRF2 activation in cancer. This nuanced modulation may allow resveratrol to walk the line between antioxidant protection and cancer suppression. More research is still needed, but the current evidence suggests resveratrol may have a sophisticated balancing act in managing NRF2 signaling for potential therapeutic benefit.
Which Foods contain Resveratrol?
| Plants | Resveratrol Content (per 100 g) |
|---|---|
| Mulberries | 5 mg |
| Lingonberries | 3 mg |
| Cranberries | 1.92 mg |
| Red currants | 1.57 mg |
| Bilberries | 0.67 mg |
| Blueberries | 0.383 mg |
| Peanuts | 1.12 mg |
| Pistachios | 0.11 mg |
| Fresh grapes | 0.15 to 0.78 mg |
| Red grape juice | 0.05 mg |
| Japanese knotweed | 1000 to 2000 mg |
Stilbenes, in particular trans-resveratrol and its glucoside, are widely reported to be beneficial to health, having been shown to possess antioxidative, anticarcinogenic, and antitumor properties. Major dietary sources include grapes, wine, peanuts, and soy; however, they can also be introduced into the diet through Itadori tea, which has long been used in Japan and China as a traditional herbal remedy for heart disease and strokes. Analysis of grapes, peanuts, and Itadori tea shows that they contain mainly trans-resveratrol glucoside. In contrast, red wines are primarily a source of the aglycones cis- and trans-resveratrol. While peanuts and grapes contain low levels of the stilbenes, Itadori tea and red wine both supply relatively high concentrations of resveratrol.
(Burns 2002)
Itadori Tea:
Japanese knotweed tea is known as Itadori tea in Japan. “Itadori” is the Japanese name for Japanese knotweed (Reynoutria japonica). This tea has been traditionally consumed in Japan for its health benefits, which are largely attributed to its high resveratrol content.
Ingredients: Made from the dried and powdered root or shoots of Japanese knotweed.
Preparation: The powder or dried plant parts are steeped in hot water to make the tea.
Health Benefits: Itadori tea is consumed for its potential antioxidant, anti-inflammatory, and cardiovascular benefits, mainly due to the presence of resveratrol.
Itadori tea is appreciated not only for its health benefits but also for its traditional value in Japanese culture.
Further Reading:
Burns J., Yokota T., Ashihara H., Lean M.E., Crozier A. Plant foods and herbal sources of resveratrol. J Agric Food Chem. 2002;50:3337–3340. doi: 10.1021/jf0112973.
Banerjee S., Bueso-Ramos C., Aggarwal B.B. Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: Role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res. 2002;62:4945–4954.
Whitsett T., Carpenter M., Lamartiniere C.A. Resveratrol, but not EGCG, in the diet suppresses DMBA-induced mammary cancer in rats. J. Carcinog. 2006;5:15. doi: 10.1186/1477-3163-5-15.
Bonkowski M.S., Sinclair D.A. Slowing ageing by design: The rise of NAD(+) and sirtuin-activating compounds. Nat. Rev. Mol. Cell Biol. 2016;17:679–690. doi: 10.1038/nrm.2016.93.
Hosseini H., Teimouri M., Shabani M., Koushki M., Babaei Khorzoughi R., Namvarjah F., Izadi P., Meshkani R. Resveratrol alleviates non-alcoholic fatty liver disease through epigenetic modification of the NRF2 signaling pathway. Int. J. Biochem. Cell Biol. 2020;119:105667. doi: 10.1016/j.biocel.2019.105667.
Singh B., Shoulson R., Chatterjee A., Ronghe A., Bhat N.K., Dim D.C., Bhat H.K. Resveratrol inhibits estrogen-induced breast carcinogenesis through induction of NRF2-mediated protective pathways. Carcinogenesis. 2014;35:1872–1880. doi: 10.1093/carcin/bgu120.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. The information contained herein is based on research findings from studies conducted in vitro (in a laboratory setting) and in animal models. Human clinical trials are necessary to determine the efficacy and safety of luteolin for the prevention and treatment of health conditions. Always consult with a healthcare professional before starting any new dietary supplement or health regimen.