- Comment: Most people think that resveratrol, the active ingredient in blueberries and red wine, is an antioxidant itself. This paper suggests that resveratrol is a mild pro-oxidant instead, which stimulates the cell's Nrf-2 antioxidant capacity. This triggers cells to produce glutathione, the body's most potent detoxification and antioxidant chemical, which in turns fights oxidation and DNA damage.
- However, all the latest research agrees with this finding: polyphenols and carotenoids do not act as antioxidant themselves inside the body, they instead act either as anti-inflammtory or they trigger the Nrf-2 system which then boosts detoxification and antioxidant capacity.
- Source: Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress
- Abstract: Resveratrol has gained tremendous interest owing to multiple reported health-beneficial effects. However, the underlying key mechanism of action of resveratrol remained largely controversial. Here, we demonstrate that under physiologically relevant conditions major biological effects of resveratrol can be attributed to the generation of oxidation products such as reactive oxygen species (ROS). At low hormetic concentrations (< 50 µM), treatment with resveratrol increased cell viability in a set of representative cell models, whereas application of quenchers of ROS completely truncated these beneficial effects. Notably, application of resveratrol led to mild, Nrf2-specific cellular gene expression reprogramming. For example, in primary human epidermal keratinocytes this resulted in a 1.3-fold increase of endogenous metabolites such as glutathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61 mV mmol GSH per g protein. After external application of oxidative stress by using 0.8% (v/v) ethanol, endogenous generation of ROS was consequently reduced by 24% in resveratrol pre-treated cells. In contrast to the common perception that resveratrol acts mainly as a chemical antioxidant or as a target protein-specific ligand, we propose that effects from resveratrol treatment are essentially based on oxidative triggering of cells. In relevant physiological microenvironments this effect can lead to hormetic shifting of cellular defence towards a more reductive state to improve resilience to oxidative stress in a manner that can be exactly defined by the redox-environment of the cell.
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