Curcumin regulates endogenous and exogenous metabolism via Nrf2-FXR-LXR pathway in NAFLD mice

Publication date: September 2018
Source:Biomedicine & Pharmacotherapy, Volume 105
Author(s): Caixia Yan, Yirui Zhang, Xiaoxu Zhang, Jiye Aa, Guangji Wang, Yuan Xie
BackgroundCurcumin is a natural polyphenol with beneficial effects on NAFLD patients and NAFLD is accompanied by metabolism decompensation.MethodsThis 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.ResultsOur 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-1c and FAS. Further, FXR, SHP and Nrf2 expressions were remarkably dropped in HFHFr-fed mice and LXRα expression was significantly enhanced, while curcumin treatment was quite effective to restore this pathway. In addition, LXRα antagonist GGPP pretreatment weakened the curcumin effects on CYP3A, CYP7A and SREBP-1c.ConclusionsThese findings indicate that the Nrf2/FXR/LXRα pathway might synergistically regulate both endogenous and exogenous metabolism in NAFLD mice and LXRα may be a novel therapeutic target of curcumin for the prevention and treatment of NAFLD.



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