Ameliorative effects of Qingganjiuwei powder, a traditional Mongolian medicine, against CCl4-induced liver fibrosis in rats

Abstract

Ethnopharmacological relevance: Qingganjiuwei powder (QGJWS) is a well-known traditional drug containing nine kinds of medicinal materials. This drug is commonly used in the Inner Mongolia region and exerts remarkable clinical effects on hepatic protection.

Aim of the study: To investigate whether QGJWS inhibits liver fibrosis in rats and to reveal its potential mechanisms.

Methods: Liver fibrosis model was induced by CCl₄ for 8 weeks in SD rats. 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, the rats were sacrificed, and serum aminotransferase (ALT and AST) levels, histopathological changes as well as the mRNA and protein expression of matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinase1 (TIMP1), collagen type Ⅰ(COL1), α-smooth muscle actin (α-SMA), combined with phosphorylation levels of extracellular signal-regulated kinase (ERK), C-Jun amino-terminal kinases (JNKs) and stress-activated protein kinase-2 (p38) protein in liver tissues were measured in each groups, respectively.

Results: The symptoms and signs of the model rats were consistent with the diagnostic criteria of liver fibrosis. By contrast, treatment with QGJWS clearly improved the general condition of rats. Also, the morphology and structure of liver can be ameliorated, there are fewer hepatocyte necrosis and lymphocytic infiltration and pseudolobuli in QGJWS treatment groups as demonstrated by histopathological analysis, thus helping bring about lower METAVIR scores. QGJWS administration also dramatically decreased serum ALT and AST levels. Further immunohistochemistry, western blotting and Real-Time PCR analysis revealed that QGJWS significantly enhanced the mRNA and protein expression of MMP2, MMP9, and downregulated the expression levels of COL1, TIMP1 and α-SMA. Furthermore, QGJWS reduced the activities of mitogen-activated protein kinases (MAPKs) pathway in liver by inhibited the phosphorylation of ERK, JNKs and p38 proteins.

Conclusions: QGJWS offers notable protection against CCl₄-induced liver fibrosis in rats, which may be due to its ability to inhibited the MAPKs signaling pathway.

Keywords: Liver fibrosis; MAPKs; Mongolian medicine; Qingganjiuwei powder; Traditional medicine.