Tea polyphenols ameliorate hydrogen peroxide-and constant darkness-triggered oxidative stress via modulating the Keap1/Nrf2 transcriptional signaling pathway in HepG2 cells and mice liver

Tea polyphenols, which are natural plant flavonoids found in the leaves of tea plants, possess bioactivities that affect the pathogenesis of several chronic diseases. However, the beneficial effects of tea polyphenols in balancing redox status and the intervention of apoptosis in the liver of mice housed in constant darkness and H2O2-stimulated HepG2 cells remain to be elucidated. The results demonstrated that TP significantly reversed decreases in H2O2-elicited cell viability, mitochondrial dysfunction, activation of NFkB and MAPK stress pathways via balancing cellular redox status. Moreover, pretreatment with TP could modulate the nuclear translocation of Nrf2 by stimulating the ERK1/2 pathway and thus transcriptionally regulate the downstream expression of antioxidant enzymes including HO-1 and NQO-1 in HepG2 cells. In addition, in vivo studies revealed that mice exposed to constant darkness, which simulated disruption due to shift work in humans, had remarkably elevated levels of H2O2 and reduced nuclear translocation of Nrf2 and its downstream phase II detoxification enzymes HO-1 and NQO-1 in liver tissue. Notably, supplementation with TP via drinking water eliminated these changes. Overall, our results indicated that TP ameliorated oxidative stress triggered by H2O2 and constant darkness via mediating Keap1/Nrf2 transcriptional pathways and regulating the expression of downstream enzymes, which indicated that treatment with TP could represent a nutritional preventive strategy in liver pathology related to oxidative stress.