Study On The Effect Of Methyl Ferulic Acid On Liver Fibrosis

Objective: To investigate the effect of Methyl ferulic acid on hepatic fibrosis in rats and to explore the preventive and therapeutic effects with mechanism of the compounds.Methods: Sixty Sprague-Dawley male rats without specific pathogen were randomly divided into normal group,model group,high and low doses of Methyl ferulic acid group,there are 15 rats in each group.The model group,the high and low doses of Methyl ferulic acid group were received ethanol gavage daily,and subcutaneous injection of CCl4 twice a week to induce hepatic fibrosis for 10 weeks.From the 7th week,the high and low doses of Methyl ferulic acid group were given 20mg/kg and 10mg/kg orally for 4 consecutive weeks.At the end of the experiment,the liver tissue was stained with H&E and Masson to observe the pathomorphological status,calculating the liver index and spleen index.TUNEL assay was used to assess apoptosis in liver tissue.Biochemical analysis was used to detect the levels of transaminase such as ALT,AST,the levels of antioxidants such as CAT,GSH,GSH-PX,SOD,T-AOC,the levels of oxidation products such as MDA,ROS.Enzyme-linked immunosorbent assay was used to detect the levels of inflammatory cytokines,such as TNF-?,MCP-1,IL-1?,IL-6,and the levels of hepatic fibrosis markers,such as HA,LN,PIIINP,C-?V,Hyp.RT-PCR and Western Blotting were used to detect the expression of NOX4,p22 phox,?-SMA,MMP-2,TIMP-1,COL-I,COL-III,Bcl-2,Bax.Western Blotting assay were used to detect the smad2/3,p38 MAPK pathway phosphorylation.Results:(1)Anti-liver fibrosis: In the high and low doses group,the proliferation of liver fibers in rats was reduced,and Methyl ferulic acid could reduce the levels of HA,LN,PIIINP,C-??,Hyp and could inhibit the expression of ?-SMA,MMP-2,TIMP-1,COL-I and COL-III in liver tissue.(2)Effect of anti-inflammation and anti-apoptosis: Methyl ferulic acid could reduce the contents of ALT,AST and TNF-?,MCP-1,IL-1? and IL-6 in serum,and inhibit the apoptosis of hepatocytes with the expression of Bcl-2,Bax in liver tissue.(3)Balance of oxidative stress: Methyl ferulic acid could increase the levels of CAT,SOD,GSH,GSH-PX and T-AOC in liver tissue,decreased the content of MDA and ROS,and inhibit the expression of NOX4 and p22 phox.(4)Mechanism: Methyl ferulic acid can inhibit the phosphorylation of smad2/3,p38 MAPK signaling pathway.Conclusions: Methyl ferulic acid could effectively protect liver function,inhibit liver inflammation and apoptosis,significantly clear the extracellular matrix of the liver,and thus play a preventive and therapeutic effect on hepatic fibrosis in rats,and its mechanism may be related to balance oxidative stress and inhibit smad2/3,p38 MAPK signaling pathway.