Key Laboratory of Forest Plant Ecology, Ministry of Education, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
Key Laboratory of Forest Plant Ecology, Ministry of Education, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; The college of Forestry, Beijing Forestry University, Beijing 100083, PR China.
Environ Toxicol Pharmacol. 2018 Jun;60:110-117. doi: 10.1016/j.etap.2018.04.016. Epub 2018 Apr 22.
In this study, the beneficial effect of paeonol on acute alcohol-induced liver injury and the basic mechanisms were investigated. in vitro, HepG2 cells were treated with paeonol for 24 h before it were exposed to alcohol for 24 h. in vivo, male C57BL/6 mice were used to establish alcohol-induced liver injury models by oral gavage of alcohol (5 g/kg BW). Paeonol pretreatment showed statistically significant reduction in alcohol-induced ROS, MDA, IL-1β, IL-6, TNF-α, and nitric oxide, while GSH content was retained (P < 0.05). Furthermore, paeonol treatment resulted in the increase of Nrf2 nuclear translocation, the increase of NQO-1 and HO-1 expression, and the suppression of NF-κB p65 nuclear translocation. However, pretreatment with NAM (inhibitor of SIRT1) not only inhibited the effect of paeonol on reducing nuclear translocation of NF-κBp65, but also inhibited the effect of paeonol on promoting the expression of nuclear Nrf2, NQO1 and HO-1. Besides, paeonol pretreatment at test doses significantly ameliorated alcohol-induced edema, hepatocyte necrosis and hepatic cord irregular. These results demonstrated that paeonol has the high potential for relieving acute alcohol-induced liver injury.
本研究旨在探讨丹皮酚对急性酒精性肝损伤的有益作用及其基本机制。体外，HepG2 细胞用丹皮酚处理 24 h 后，再用酒精处理 24 h。体内，雄性 C57BL/6 小鼠通过灌胃酒精（5 g/kg BW）建立酒精性肝损伤模型。丹皮酚预处理可显著降低酒精诱导的 ROS、MDA、IL-1β、IL-6、TNF-α 和一氧化氮水平，同时维持 GSH 含量（P < 0.05）。此外，丹皮酚处理可增加 Nrf2 核易位，增加 NQO-1 和 HO-1 的表达，并抑制 NF-κB p65 核易位。然而，SIRT1 抑制剂 NAM 预处理不仅抑制了丹皮酚降低核易位 NF-κB p65 的作用，也抑制了丹皮酚促进核 Nrf2、NQO1 和 HO-1 表达的作用。此外，丹皮酚在测试剂量下预处理可显著改善酒精引起的肝水肿、肝细胞坏死和肝索不规则。这些结果表明丹皮酚具有缓解急性酒精性肝损伤的巨大潜力。
