Antioxidant activities of ginsenoside Rg1 against cisplatin-induced hepatic injury through Nrf2 signaling pathway in mice
Antioxidant activities of ginsenoside Rg1 against cisplatin-induced hepatic injury through Nrf2 signaling pathway in mice
复制标题
人参皂苷Rg1通过Nrf2信号通路对抗顺铂诱导的小鼠肝损伤的抗氧化活性
DOI：
10.1080/10715762.2016.1234710
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发表时间：
2017-01-01
影响因子：
3.3
通讯作者：
Chen, Naihong
中科院分区：
文献类型：
--
作者：
Gao, Yan;Chu, Shifeng;Chen, Naihong
摘要 氧化应激主要由活性氧（ROS）引起。这种损害会对正常器官造成净压力，导致重要生理功能逐渐丧失。 ROS，如自由基，代表一类源自氧代谢并固有存在的分子。然而，过量产生的ROS会损害所有需氧生物。人参是最常用的替代草药之一，也是一种传统中药。本研究的目的是探讨人参皂苷 Rg1 对顺铂引起的肝损伤的抗氧化潜力。用顺铂治疗雄性小鼠以诱导氧化应激，以模拟抗癌药物顺铂的副作用。人参皂苷 Rg1 有效预防顺铂引起的肝毒性，减轻组织学病变。 Rg1的抗氧化功能受到p62-Keap1-Nrf2信号通路激活的抑制，同时伴随着蛋白产物的表达。肝细胞中p62的积累和JNK活化的增加促进了Nrf2的活化。另一方面，Nrf2 的降解是由酪氨酸磷酸化、泛素和 Keap1 引导的。总之，Rg1主要通过抑制Keap1和Nrf2的结合来预防肝毒性，部分是通过p62积累，更重要的是通过增加与Nrf2相关的抗氧化蛋白的产生。 Nrf2的药理激活是对抗肝损伤的有效方法。
Abstract Oxidative stress is mainly caused by reactive oxygen species (ROS). The damage causes a net stress on normal organs, leading to a gradual loss of vital physiological function. ROS, such as free radicals, represent a class of molecules which are derived from the metabolism of oxygen and exist inherently. However, excessive produced ROS can damage all aerobic organisms. Ginseng is one of the most commonly used alternative herbal medicines, also as a traditional Chinese medicine. The aim of this study is to investigate the antioxidant potential function of ginsenoside Rg1 against cisplatin-caused hepatic damage. Male mice were treated with cisplatin to induce oxidative stress to mimic the side effect of anti-cancer drug cisplatin. Ginsenoside Rg1 effectively prevented against cisplatin-induced hepatotoxicity, alleviating histological lesions. Antioxidant functions of Rg1 were restrained by the activation of p62–Keap1–Nrf2 signaling pathway, simultaneously accompanied with expression of protein products. Accumulative p62 and increased activation of JNK in hepatocytes promoted the activation of Nrf2. For the other, degradation of Nrf2 was guided by tyrosine phosphorylation, ubiquitin, and Keap1. In summary, Rg1 prevents hepatotoxicity mainly by inhibiting the binding of Keap1 and Nrf2, partly by p62 accumulation, and more importantly by increasing the production of antioxidative proteins associated to Nrf2. Pharmacological activation of Nrf2 is an effective way in combating against liver injury.