title: Wogonoside Shows Antifibrotic Effects in an Experimental Regression Model of Hepatic Fibrosis.
abstract: BACKGROUND
  Wogonoside (WO), a flavonoid extracted from Huangqin, plays multiple physiological roles. However, it has remained elusive how WO regulates hepatic fibrogenesis until now.
  
  
  OBJECTIVE
  The purpose of the study was to investigate the potential protective effects of WO against liver fibrosis induced by carbon tetrachloride (CCl4).
  
  
  METHODS
  In this study, male rats were randomly allocated into four groups: a control group, the CCl4 group, the CCl4 and WO (4 mg/kg) group, and CCl4 and WO (8 mg/kg) group. Hepatic fibrosis was induced by subcutaneous injection of CCl4 twice a week for a continuous 6-week period. Then the rats were intragastrically administrated with WO daily for 4 weeks before being killed.
  
  
  RESULTS
  As expected, histopathological assessment, Masson trichrome staining, and Sirius red staining demonstrated that WO drastically ameliorated the hepatic fibrosis caused by CCl4. WO significantly attenuated the CCl4-induced upregulations of liver indices including alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin-1β, IL-6, hexadecenoic acid and laminin in serum, as well as hydroxyproline, malondialdehyde and phosphatidylinositol 3-kinase (PI3K)/protein Kinase B(Akt)/mechanistic target of rapamycin (mTOR)/nuclear factor-kappa B signalings in liver. Meanwhile, WO also effectively recovered the depletions of superoxide dismutase, glutathione and IL-10. Furthermore, we evaluated the effects of WO on the alpha smooth muscle actin, type I collagen expressions, and PI3K/Akt/ mTOR/ribosomal protein S6 kinase 70 kDa (p70S6K) signaling in transforming growth factor (TGF-β) stimulated hepatic stellate cell-T6 cells.
  
  
  CONCLUSIONS
  These results suggested that WO had significant protective effects against liver fibrosis induced by CCl4.
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Qichao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Resources Science of Traditional Chinese Medicines, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wen
authors.affiliation: Department of Natural Medicinal Chemistry, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China. xianminzhu@hotmail.com.
authors.forename: Xianmin
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen / Q000097:blood; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D015415:Biomarkers; D044950:Flavanones; D005960:Glucosides; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; D020011:Protective Agents; D003094:Collagen; D002251:Carbon Tetrachloride; C473995:wogonoside
keywords: Carbon tetrachloride; HSC-T6; Hepatic fibrosis; PI3K/Akt/mTOR; TGF-β; Wogonoside