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

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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-β), type I TGF-β receptor (TβR-1), type II TGF-β receptor (TβR-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 CCl4 group showed a significant increase in hepatotoxicity
biomarkers and up-regulation of the expression of genes encoding TGF-β, TβR-I, TβR-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‐β1/Smad signaling
pathway in the CCl4‐induced liver fibrosis model. The major target was the inhibition of the expression of
TGF‐β1, Smad2, and Smad3.
Keywords: Ginseng extract, Carbon tetrachloride, Gene expression, Real time PCR

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