Tea polyphenols ameliorates neural redox imbalance and mitochondrial dysfunction via mechanisms linking the key circadian regular Bmal1

Abstract

Circadian rhythms are autonomous anticipatory oscillators that control a large array of physiological and metabolic processes. Compelling evidence points toward an interplay between circadian rhythms and cellular redox metabolism. Dysregulation of circadian rhythms is associated with neurodegenerative diseases and accelerated aging. Tea polyphenols (TP) is one of the most used antioxidants and exerts beneficial effect on neurodegenerative diseases. The aim of this study is to investigate whether circadian clock mechanisms are involved in the protection effect of TP against neural redox imbalance and mitochondrial dysfunction in SH-SY5Y cells. In the current study, our results revealed that TP, as a Bmal1-enhancing natural compound, can reverse the relatively shallow daily oscillations of circadian clock genes transcription and protein expression in SH-SY5Y neuronal cells under oxidative stress conditions. Furthermore, TP pretreatment significantly ameliorated H2O2-elicited mitochondria impairment via manipulating mitochondrial dynamics and mitochondrial membrane potential, which is consistent with the recovery in expression of mitochondrial respiration complex I-IV in Bmal1-dependent efficiency. Furthermore, Bmal1 is involved in TP-stimulated Nrf2/ARE/HO-1 and AKT/CREB/BDNF signaling pathway. Hence, TP may serve as a nutritional preventive strategy in the recovery of oxidative stress-related neurodegenerative disease via modulating circadian clock.