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Attenuation of tert-Butyl Hydroperoxide (t-BHP)-Induced Oxidative Damage in HepG2 Cells by Tangeretin: Relevance of the Nrf2–ARE and MAPK Signaling Pathways
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2018-06-06 00:00:00 , DOI: 10.1021/acs.jafc.8b01875
Fuqiang Liang 1 , Yajing Fang 1 , Weiwei Cao 1 , Zhuo Zhang 1 , Siyi Pan 1 , Xiaoyun Xu 1
Affiliation  

The current study evaluates the protective effects of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells and the potential mechanisms of this protection. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive-oxygen-species (ROS) levels, lactate dehydrogenase (LDH) leakage and glutathione (GSH) levels. Further mechanistic studies showed that tangeretin up-regulated the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Moreover, tangeretin induced antioxidant-responsive-element (ARE)-dependent luciferase activation, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly due to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK–Nrf2–ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.

中文翻译:

桔皮素对丁基过氧化氢(t -BHP)诱导的HepG2细胞氧化损伤的减弱:Nrf2-ARE和MAPK信号通路的相关性

目前的研究评估了橘皮苷(一种主要从柑橘类果皮中分离出来的代表性聚甲氧基黄酮(PMF))对丁基过氧化氢(t- BHP)诱导的HepG2细胞氧化损伤的保护作用以及这种保护作用的潜在机制。橘子抑制t-BHP诱导的氧化损伤,通过细胞活力,活性氧(ROS)水平,乳酸脱氢酶(LDH)泄漏和谷胱甘肽(GSH)水平进行评估。进一步的机理研究表明,橘红素上调了血红素加氧酶1(HO-1)和NAD(P)H醌氧化还原酶1(NQO1)的表达。此外,橘皮苷诱导抗氧化剂响应元件(ARE)依赖的萤光素酶激活,核因子(类胡萝卜素衍生的2)样2(Nrf2)核易位以及促分裂原激活的蛋白激酶(MAPK)磷酸化。研究结果表明,橘皮苷的保护作用至少部分是由于其通过MAPK–Nrf2–ARE信号通路上调抗氧化酶NQO1和HO-1的能力。橘皮素可能在肝损伤中起有效的保护作用。
更新日期:2018-06-06
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