Curcumin regulates endogenous and exogenous metabolism via Nrf2-FXR-LXR pathway in NAFLD mice
Curcumin regulates endogenous and exogenous metabolism via Nrf2-FXR-LXR pathway in NAFLD mice
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姜黄素通过 Nrf2-FXR-LXR 通路调节 NAFLD 小鼠内源性和外源性代谢
DOI：
10.1016/j.biopha.2018.05.135
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发表时间：
2018-09-01
影响因子：
7.5
通讯作者：
Xie, Yuan
中科院分区：
文献类型：
--
作者：
Yan, Caixia;Zhang, Yirui;Xie, Yuan
背景资料：姜黄素是一种天然多酚类物质，对NAFLD患者有一定的治疗作用，而NAFLD患者常伴有代谢失代偿。方法：采用高脂高果糖饮食（HFHFr）诱导的C57 BL/6小鼠非酒精性脂肪性肝病模型和体外培养的小鼠肝细胞，观察姜黄素对内源性胆汁酸代谢途径和外源性外源性生物素代谢途径的影响。我们的研究结果表明，姜黄素治疗明显减弱了HFHFFr喂养小鼠的肝脏脂肪变性，并逆转了血清生化指标的异常。姜黄素能有效逆转脂肪肝患者肝脏CYP 3A、CYP 7A的表达，恢复代谢能力。与此同时，脂质合成已被姜黄素控制，通过CD 36、SREBP-lc和FAS的表达证明。此外，在HFHFFr喂养的小鼠中，FXR、SHP和Nrf 2表达显著下降，LXR α表达显著增强，而姜黄素治疗对恢复该途径非常有效。结论：Nrf 2/FXR/LXR α通路可能协同调节NAFLD小鼠内源性和外源性代谢，LXR α可能成为姜黄素防治NAFLD的新靶点。
Background: Curcumin is a natural polyphenol with beneficial effects on NAFLD patients and NAFLD is accompanied by metabolism decompensation.Methods: This study was focused on the effect of curcumin on the relationship between endogenous bile acids metabolism pathway and exogenous xenobiotics metabolism pathway in C57BL/6 mice of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet (HFHFr) and in cultured mice hepatocytes.Results: Our results showed curcumin treatment apparently attenuated the hepatic steatosis and reversed the abnormalities of serum biochemical parameters in HFHFr-fed mice. Curcumin effectively reversed the expression of CYP3A and CYP7A in fatty liver status to restore metabolism capability. In the meantime, lipid synthesis has been controlled by curcumin, evidenced by the expression of CD36, SREBP-lc and FAS. Further, FXR, SHP and Nrf2 expressions were remarkably dropped in HFHFr-fed mice and LXR alpha expression was significantly enhanced, while curcumin treatment was quite effective to restore this pathway. In addition, LXR alpha antagonist GGPP pretreatment weakened the curcumin effects on CYP3A, CYP7A and SREBP-1c.Conclusions: These findings indicate that the Nrf2/FXR/LXR alpha pathway might synergistically regulate both endogenous and exogenous metabolism in NAFLD mice and LXR alpha may be a novel therapeutic target of curcumin for the prevention and treatment of NAFLD.