title: Effect of ginseng extract on the TGF-β1 signaling pathway in CCl4-induced liver fibrosis in rats.
abstract: 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, CCl4group 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 CCl4group. The CCl4group 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, CCl4administration 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Hafez
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.|Department of Zoology, College of Science, Alexandria University, Alexandria, Egypt.
authors.forename: Sherifa S
authors.initials: SS
authors.lastname: Hamed
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.|College of science, Zoology and Entomology department, Helwan University, Cairo, Egypt.
authors.forename: Manal F
authors.initials: MF
authors.lastname: El-Khadragy
authors.affiliation: National Cancer Institute, Virology and Immunology Unit, Cancer Biology Department, Cairo University, Cairo, Egypt.
authors.forename: Zeinab K
authors.initials: ZK
authors.lastname: Hassan
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia.
authors.forename: Salim S
authors.initials: SS
authors.lastname: Al Rejaie
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Sayed-Ahmed
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia.
authors.forename: Naif O
authors.initials: NO
authors.lastname: Al-Harbi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Al-Hosaini
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Al-Harbi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia.
authors.forename: Ali R
authors.initials: AR
authors.lastname: Alhoshani
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. shabanah@ksu.edu.sa.
authors.forename: Othman A
authors.initials: OA
authors.lastname: Al-Shabanah
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia.
authors.forename: Shakir Dekhal
authors.initials: SD
authors.lastname: Alsharari
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D010936:Plant Extracts; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D002251:Carbon Tetrachloride; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat
keywords: Carbon tetrachloride; Gene expression; Ginseng extract; Real time PCR