Effect of ginseng extract on the TGF-β1 signaling pathway in CCl4-induced liver fibrosis in rats

Background: Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)induced liver fibrosis in rats. Methods: Male Wistar rats were divided into four groups: control group, ginseng group, CCl4 group and CCl4+ ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl4 (30% in olive oil) weekly for 8 weeks. The control group was I.P injected with olive oil. The expression of genes encoding transforming growth factor beta (TGF-beta), type I TGF-beta receptor (T beta R-1), type II TGF-beta receptor (T beta R-II), mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad4, matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), Collagen 1a2 (Col1a2), Collagen 3a1 (Col3a1), interleukin-8 (IL-8) and interleukin -10 (IL-10) were measured by real-time PCR. Results: Treatment with ginseng extract decreased hepatic fat deposition and lowered hepatic reticular fiber accumulation compared with the CCl4 group. The CC(l)4 group showed a significant increase in hepatotoxicity biomarkers and up-regulation of the expression of genes encoding TGF-beta, T beta R-I, T beta R-II, MMP2, MMP9, Smad-2,3, -4, and IL-8 compared with the control group. However, CCl4 administration resulted in the significant down-regulation of IL-10 mRNA expression compared with the control group. Interestingly, ginseng extract supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. Conclusion: ginseng extract had an anti-fibrosis effect via the regulation of the TGF-beta 1/Smad signaling pathway in the CCl4-induced liver fibrosis model. The major target was the inhibition of the expression of TGF-beta 1, Smad2, and Smad3.