College of Pharmacy, Guilin Medical University, Guilin, 541004, PR China.
College of Pharmacy, Guilin Medical University, Guilin, 541004, PR China.
Chem Biol Interact. 2018 Aug 1;291:180-189. doi: 10.1016/j.cbi.2018.06.028. Epub 2018 Jun 27.
Methyl ferulic acid (MFA) is a biologically active monomer extracted and purified from the Chinese herbal medicine Securidaca inappendiculata hasskarl. The previously studies showed that MFA improved acute liver injury induced by ethanol. However, the effect of MFA on ethanol-induced hepatic steatosis in alcoholic liver disease (ALD) still remains unclear. The current study was aimed at elucidating the effect of MFA on alcohol-induced hepatic steatosis and the underlying mechanisms. Human hepatocyte L-02 cells exposed to 200 mM ethanol for 24 h to simulate alcoholic steatosis in vitro. SD rats were fed a Lieber-DeCarli diet containing 5% (w/v) alcohol for 16 weeks to induce alcoholic liver disease in vivo. We examined the effect of MFA on ethanol-induced lipid deposition in L-02 cells and SD rats. The results showed that MFA reduced the accumulation of lipid in L-02 cells, improved alcoholic liver injury in rats, alleviated hepatic pathological lesions, and reduced lipid deposition in rat serum and liver. Further studies suggest that MFA reduces lipid synthesis by activating AMPK-ACC/MAPK-FoxO1 pathway. In addition, MFA also promotes lipid oxidation by up-regulating the expression of SIRT1, PPAR-α, and CPT-1α. Taken together, MFA ameliorates ethanol-induced hepatic steatosis by activating AMPK-ACC/MAPK-FoxO1 pathway and up-regulating the expression levels of SIRT1, PPAR-α, and CPT-1α.
甲基阿魏酸(MFA)是从中药三叶崖爬藤中提取和纯化的一种具有生物活性的单体。先前的研究表明,MFA 可改善乙醇引起的急性肝损伤。然而,MFA 对酒精性肝病(ALD)中乙醇诱导的肝脂肪变性的影响尚不清楚。本研究旨在阐明 MFA 对酒精诱导的肝脂肪变性的影响及其潜在机制。体外,将人肝细胞 L-02 细胞用 200mM 乙醇孵育 24h 以模拟酒精性脂肪变性。SD 大鼠给予含 5%(w/v)酒精的 Lieber-DeCarli 饮食 16 周,以诱导体内酒精性肝病。我们检测了 MFA 对 L-02 细胞和 SD 大鼠乙醇诱导的脂质沉积的影响。结果表明,MFA 减少了 L-02 细胞内脂质的积累,改善了大鼠的酒精性肝损伤,减轻了肝组织病理学损伤,减少了大鼠血清和肝脏中的脂质沉积。进一步的研究表明,MFA 通过激活 AMPK-ACC/MAPK-FoxO1 通路来减少脂质合成。此外,MFA 还通过上调 SIRT1、PPAR-α 和 CPT-1α 的表达来促进脂质氧化。总之,MFA 通过激活 AMPK-ACC/MAPK-FoxO1 通路和上调 SIRT1、PPAR-α 和 CPT-1α 的表达水平来改善乙醇诱导的肝脂肪变性。