Liver fibrosis is a pathological wound-healing response caused by chronic liver damage due to a virus, autoimmune disorder, or drugs. Hepatic stellate cells (HSCs) play an essential role in the pathogenesis of liver fibrosis. Methyl ferulic acid (MFA), a biologically active monomer, has a protective effect on liver injury. However, the effects and roles of MFA in liver fibrosis remain unknown. The purpose of the current study was to investigate the effect of MFA on hepatic fibrosis and the underlying mechanisms. Human hepatic stellate LX-2 cells were exposed to 5 μg/L TGF-β1 for 48 h to stimulate liver fibrosis in vitro. Using MTT, RT-PCR and Western blot analysis, we revealed that MFA significantly inhibited the proliferation of LX-2 cells as well as decreased the expressions of α-SMA and type I collagen in LX-2 cells. SD rats were fed with ethanol, and this combined with the intraperitoneal injection of CCl₄ induced liver fibrosis in vivo. We found that the administration of MFA markedly decreased the levels of hyaluronic acid (HA), procollagen type III (PC-III), type IV collagen (CIV) and laminin (LN) in the serum, inhibited the expression of α-smooth muscle actin (α-SMA) as well as type I and type III collagen, and up-regulated the ratio of MMP-2/TIMP-1 in rats. The antifibrotic effects of MFA were also evaluated by H&E staining and Masson's trichrome staining. In addition, further studies suggested that this protection by MFA from liver fibrosis was possibly related to the inhibition of TGF-β1/Smad and NOX4/ROS signalling. In conclusion, our results demonstrate that MFA attenuated liver fibrosis and hepatic stellate cell activation by inhibiting the TGF-β1/Smad and NOX4/ROS signalling pathways.

肝纤维化是由病毒，自身免疫性疾病或药物引起的慢性肝损伤引起的病理性伤口愈合反应。肝星状细胞（HSC）在肝纤维化的发病机理中起着至关重要的作用。甲基阿魏酸（MFA）是一种生物活性单体，对肝损伤具有保护作用。但是，MFA在肝纤维化中的作用和作用仍然未知。本研究的目的是调查MFA对肝纤维化的影响及其潜在机制。将人肝星状LX-2细胞暴露于5μg/ LTGF-β148小时以在体外刺激肝纤维化。使用MTT，RT-PCR和Western印迹分析，我们发现MFA显着抑制了LX-2细胞的增殖，并降低了LX-2细胞中α-SMA和I型胶原的表达。SD大鼠饲喂乙醇，并与腹腔注射CCl _4一起在体内诱导肝纤维化。我们发现，MFA的使用显着降低了血清中的透明质酸（HA），III型前胶原（PC-III），IV型胶原（CIV）和层粘连蛋白（LN）的水平，抑制了α平滑肌的表达肌动蛋白（α-SMA）以及I型和III型胶原蛋白，并上调了大鼠MMP-2 / TIMP-1的比例。还通过H＆E染色和Masson三色染色评价了MFA的抗纤维化作用。此外，进一步的研究表明，MFA对肝纤维化的这种保护作用可能与抑制TGF-β1/ Smad和NOX4 / ROS信号传导有关。总之，我们的结果表明，MFA通过抑制TGF-β1/ Smad和NOX4 / ROS信号通路来减轻肝纤维化和肝星状细胞的活化。