Intracellular Polyphenol Wine Metabolites Oppose Oxidative Stress and Upregulate Nrf2/ARE Pathway

Moderate wine consumption has been associated with several benefits to human health due to its high polyphenol content. In this study, we investigated whether polyphenols contained in a particular red wine, rich in polyphenols, can pass the cell membrane and switch the oxidant/antioxidant balance toward an antioxidant pattern of THP-1 cells and human cardiomyocytes through a gene regulatory system. First, we identified which metabolite polyphenols present in red wine extract cross cell membranes and may be responsible for antioxidant effects. The results showed that the wine metabolites in treated cells belonged mainly to stilbenes, flavan-3-ols derivatives, and flavonoids. Other metabolites present in cells were not typical wine metabolites. Then, we found that red wine extract dose-dependently lowered reactive oxygen species (ROS) induced by tert-butyl hydroperoxide (TBHP) up to 50 +/- 7% in both cell lines (p < 0.01). Furthermore, wine extract increased nuclear Nrf2 of about 35 +/- 5% in both cell lines (p < 0.01) and counteracted its reduction induced by TBHP (p < 0.01). The rise in Nrf2 was paralleled by the increase in hemeoxygenase-1 and glutamate-cysteine ligase catalytic subunit gene expression (both mRNA and protein) (p < 0.01). These results could help explain the healthful activity of wine polyphenols within cells.

Automated summary

This study investigates the antioxidant effects of polyphenols in red wine by examining their ability to pass through cell membranes and regulate gene expression. The results show that red wine polyphenols, specifically stilbenes, flavan-3-ols derivatives, and flavonoids, can enter cells and lower reactive oxygen species induced by tert-butyl hydroperoxide. Additionally, red wine extract increases the expression of Nrf2, hemeoxygenase-1, and glutamate-cysteine ligase catalytic subunit genes in the cells.