Ameliorative Effects And Mechanisms Of Qingganjiuwei Powder,A Traditional Mongolian Medicine,against Liver Fibrosis In Rats

Objective: To investigate whether QGJWS inhibits liver fibrosis in rats and reveal its potential mechanisms.Methods: We first established a liver fibrosis model in rats,which involved an artificial hepatocellular injury induced by repeated CCl4 injection.Next,rats were intragastrically administered quantum satis doses of QGJWS(0.525,1.575,4.725 g/kg per day)or Silymarin(SIL;120 mg/kg per day)for 8 weeks.Afterwards,histopathological and serological analyses combined with molecular biological methods were conducted to evaluate the therapeutic effects of QGJWS.The primary HSCs were isolated by collagenase reperfusion in situ and density gradient centrifugation method,the effects 10% or 20% of QGJWS-containing serum on cell proliferation,cycle,apoptosis and ECM secretion of HSCs were assessed subsequently.Results: The results revealed the QGJWS improved liver histology of rats,decreased serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST),and dramatically enhanced the m RNA and protein expression of matrix metalloproteinase 2(MMP2),matrix metalloproteinase 9(MMP9)and downregulated the expression of collagen typeⅠ(COL1),tissue inhibitor of metalloproteinase1(TIMP1)and α-smooth muscle actin(α-SMA).Furthermore,QGJWS reduced the activity of mitogen-activated protein kinases(MAPKs)pathway by inhibited the phosphorylation of extracellular signal-regulated kinase(ERK),Jun amino-terminal kinases(JNKs)and p38 MAPK(p38).In vitro experiment,the expression of COL1 and α-SMA of HSCs of the QGJWS-containing serum group was significantly lower than the control group;QGJWS inhibited proliferation and promoted apoptosis of HSCs,and blocking the cell cycle to G0-G1 phase,and also inhibited the phosphorylation of extracellular signal-regulated kinase(ERK),Jun amino-terminal kinases(JNKs)and p38 MAPK(p38)(all P<0.05).Conclusions:(1)Our study revealed that QGJWS offers notable protection against CCl4-induced liver fibrosis in rats via alleviated liver injury and improve liver histology of rats.(2)QGJWS-containing serum reduced the expression of α-SMA and COL1,inhibited proliferation and promoted apoptosis of the HSCs,and blocked cell cycle to G0-G1 phase.(3)QGJWS effected the levels of α-SMA,COL1,MMP2,MMP9 and TIMP1 in liver tissue,and increased ECM degradation,which could be potential targets for the treatment of liver fibrosis.The potential mechanisms of QGJWS may be due to its ability to regulated the MMPs/TIMPs system and inhibited MAPKs signal pathways both in vitro and in vivo.Owing to the hepatoprotective potential of QGJWS,it may have clinical importance and offer an alternative approach to treatment of liver fibrosis.However,additional studies will be needed to determine the exact mechanism.