title: Schizandrin inhibits fibrosis and epithelial-mesenchymal transition in transforming growth factor-β1-stimulated AML12 cells.
abstract: The transforming growth factor (TGF)-β1 plays a crucial role in the induction of the epithelial-to-mesenchymal transition (EMT) in hepatocytes, which contributes to the pathogenesis of liver fibrosis. The inhibition of the TGF-β1 cascade suppresses EMT and the resultant fibrosis. Schizandrin (Sch) has various therapeutic effects on a range of medical conditions such as anti-asthmatic, anti-cancer, and anti-inflammatory effects. However, the effect of Sch on TGF-β1-stimulated hepatic fibrosis and EMT is still unknown. In the present investigation, we evaluated the anti-fibrotic and anti-EMT properties of Sch and its underlying mechanisms in murine hepatocyte AML12 cells. Overall, we found that Sch inhibited the pro-fibrotic activity of TGF-β1 in AML12 cells; thus, it suppressed the accumulation of ECM proteins. Also, Sch inhibited the EMT as assessed by reduced expression of vimentin and fibronectin, and increased E-cadherin and ZO-1 in TGF-β1 induced AML12 cells. Sch reduced TGF-β1-mediated phosphorylation of Smad2/3 and Smad3/4 DNA binding activity. On the other hand, Sch reduced TGF-β1-induced ERK1/2 and PI3K/Akt phosphorylation in the non-Smad pathway. In conclusion, Sch can antagonize TGF-β1-mediated fibrosis and EMT in AML12 cells. Sch may possess potential as an anti-fibrotic molecule in the treatment of liver fibrosis.
authors.affiliation: College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Ji-hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea. Electronic address: jwyoon@kmu.ac.kr.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Yoon
mesh_terms: D000818:Animals; D002460:Cell Line; D034242:Cyclooctanes / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis; D017705:Lignans / Q000494:pharmacology*; D008107:Liver Diseases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011083:Polycyclic Compounds / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; D034741:RNA, Small Interfering; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D053773:Transforming Growth Factor beta1; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; C011105:schizandrin
keywords: Epithelial–mesenchymal transition; Extracellular matrix; Fibrosis; Schizandrin; Transforming growth factor-β1