Abstract
BackgroundLiver 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.MethodsMale 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.ResultsTreatment 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.Conclusionginseng 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.
Highlights
Liver diseases are major global health problems
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) measurement kits were purchased from Human (Human, Wiesbaden, Germany)
CCl4 significantly increased serum lipid parameters including TG, total cholesterol (TC) and low-density lipoprotein (LDL) levels and nonsignificantly decreased the high-density lipoprotein (HDL) level compared with the control group
Summary
Liver diseases are major global health problems. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)induced liver fibrosis in rats. Several hepatotoxicants including polycyclic aromatic hydrocarbons, nitrosamines, and carbon tetrachloride (CCl4) are transformed into intermediate reactive oxygen species that have hepatotoxic effects in humans and experimental animal models [3]. For models of human disease, the rat offers many advantages over mice and other organisms, including the size of its body and substructures in organs, as well as the ability to measure drug effects at specific anatomical areas [1]. Chronic liver diseases are worldwide health problems causing approximately 800,000 deaths per year [2, 3]. Cirrhosis occurs and can cause hepatocellular carcinoma [4]. Advanced fibrosis is reversible depending on the degree of fibrosis, end-stage cirrhosis is irreversible [5]
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