State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Biochem Pharmacol. 2020 Aug;178:114058. doi: 10.1016/j.bcp.2020.114058. Epub 2020 May 26.
Celastrol, derived from the roots of the Tripterygium Wilfordi, has attracted interest for its potential anti-inflammatory and lipid-lowering activities. In the present study, the protective effect of celastrol on carbon tetrachloride (CCl)-induced acute liver injury was investigated. Celastrol improved the increased transaminase activity, inflammation, and oxidative stress induced by CCl, resulting in improved metabolic disorders found in mice with liver injury. Dual-luciferase reporter assays and primary hepatocyte studies demonstrated that the peroxisome proliferator-activated receptor α (PPARα) signaling mediated the protective effect of celastrol, which was not observed in Ppara-null mice, and co-treatment of wild-type mice with the PPARα antagonist GW6471. Mechanistically, PPARα deficiency potentiated CCl-induced liver injury through a deoxycholic acid (DCA)-EGR1-inflammatory factor axis. These data demonstrate a novel role for celastrol in protection against acute liver injury through modulating PPARα signaling.
从雷公藤根部分离得到的雷公藤红素，因其具有潜在的抗炎和降血脂活性而受到关注。本研究探讨了雷公藤红素对四氯化碳（CCl）诱导的急性肝损伤的保护作用。雷公藤红素改善了 CCl 诱导的转氨酶活性升高、炎症和氧化应激，从而改善了肝损伤小鼠的代谢紊乱。双荧光素酶报告基因检测和原代肝细胞研究表明，过氧化物酶体增殖物激活受体α（PPARα）信号转导介导了雷公藤红素的保护作用，而在 Ppara 基因敲除小鼠中未观察到这种作用，并且在野生型小鼠中用 PPARα 拮抗剂 GW6471 共同处理也未观察到这种作用。在机制上，PPARα 缺乏通过胆酸（DCA）-EGR1-炎症因子轴增强 CCl 诱导的肝损伤。这些数据表明，雷公藤红素通过调节 PPARα 信号转导在保护急性肝损伤方面具有新的作用。
