Effect of ginseng extract on the TGF-β1 signaling pathway in CCl 4 -induced liver fibrosis in rats

• Published in: BMC complementary and alternative medicine Vol. 17; no. 1; p. 45
• Main Authors: Hafez, Mohamed M, Hamed, Sherifa S, El-Khadragy, Manal F, Hassan, Zeinab K, Al Rejaie, Salim S, Sayed-Ahmed, Mohamed M, Al-Harbi, Naif O, Al-Hosaini, Khalid A, Al-Harbi, Mohamed M, Alhoshani, Ali R, Al-Shabanah, Othman A, Alsharari, Shakir Dekhal
• Format: Journal Article
• Language: English
• Published: England 13.01.2017
• Subjects: Animals; Carbon Tetrachloride - adverse effects; Humans; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-8 - genetics; Interleukin-8 - metabolism; Liver Cirrhosis - chemically induced; Liver Cirrhosis - drug therapy; Liver Cirrhosis - genetics; Liver Cirrhosis - metabolism; Male; Panax - chemistry; Plant Extracts - administration & dosage; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Rats; Rats, Wistar; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Signal Transduction - drug effects; Smad Proteins - genetics; Smad Proteins - metabolism; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Carbon tetrachloride; Real time PCR; Gene expression; Ginseng extract
• ISSN: 1472-6882

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. Male Wistar rats were divided into four groups: control group, ginseng group, CCl group and CCl  + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl (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. Treatment with ginseng extract decreased hepatic fat deposition and lowered hepatic reticular fiber accumulation compared with the CCl group. The CCl 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, CCl 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 CCl . ginseng extract had an anti-fibrosis effect via the regulation of the TGF-β1/Smad signaling pathway in the CCl -induced liver fibrosis model. The major target was the inhibition of the expression of TGF-β1, Smad2, and Smad3.