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 ameliorate hydrogen peroxide-and constant darkness-triggered oxidative stress via modulating the Keap1/Nrf2 transcriptional signaling pathway in HepG2 cells and mice liver
复制标题
茶多酚通过调节 HepG2 细胞和小鼠肝脏中的 Keap1/Nrf2 转录信号通路，改善过氧化氢和持续黑暗引发的氧化应激
DOI：
10.1039/c7ra05000c
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发表时间：
2017-01-01
期刊：
影响因子：
3.9
通讯作者：
Liu, Xuebo
中科院分区：
文献类型：
--
作者：
Qi, Guoyuan;Mi, Yashi;Liu, Xuebo
茶多酚是存在于茶树叶片中的天然植物类黄酮，具有影响多种慢性疾病发病机制的生物活性。然而，茶多酚在持续黑暗和h2o2刺激的HepG2细胞中平衡氧化还原状态和干预肝脏凋亡的有益作用仍有待阐明。结果表明，TP通过平衡细胞氧化还原状态，显著逆转h2o2诱导的细胞活力下降、线粒体功能障碍、NFkB和MAPK应激途径的激活。此外，TP预处理可以通过刺激ERK1/2通路调节Nrf2的核易位，从而转录调节HepG2细胞中HO-1、NQO-1等抗氧化酶的下游表达。此外，体内研究显示，小鼠暴露于模拟人类轮班工作的持续黑暗环境中，肝脏组织中H2O2水平显著升高，Nrf2及其下游II期解毒酶HO-1和NQO-1的核易位减少。值得注意的是，通过饮用水补充TP消除了这些变化。总的来说，我们的研究结果表明，TP通过介导Keap1/Nrf2转录途径和调节下游酶的表达，改善H2O2和持续黑暗引发的氧化应激，这表明TP治疗可能是一种与氧化应激相关的肝脏病理的营养预防策略。
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.