title: Schisandrin B suppresses TGFβ1 signaling by inhibiting Smad2/3 and MAPK pathways.
abstract: TGFβ1 plays a crucial role in the pathogenesis of vascular fibrotic diseases. Schisandra chinensis (S. chinensis), which is used as an oriental herbal medicine, is effective in the treatment of vascular injuries that cause aberrant TGFβ1 signaling. In this study, we investigated whether S. chinensis extract and its active ingredients inhibit TGFβ1 signaling in A7r5 vascular smooth muscle cells. We found that S. chinensis extract suppressed TGFβ1 signaling via inhibition of Smad2/3 phosphorylation and nuclear translocation. Among the active ingredients of S. chinensis extract, schisandrin B (SchB) most potently inhibited TGFβ1 signaling. SchB inhibited sustained phosphorylation and nuclear translocation of Smad2/3. Moreover, SchB suppressed TGFβ1-induced phosphorylation of p38 and JNK, which contributed to Smad2/3 inactivation. The present study is the first to demonstrate that S. chinensis extract and SchB inhibit TGFβ1 signaling. Our results may help future investigations to understand vascular fibrosis pathogenesis and to develop novel therapeutic strategies for treatment of vascular fibrotic diseases.
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Jung Nyeo
authors.initials: JN
authors.lastname: Chun
authors.forename: Su-Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Chul Young
authors.initials: CY
authors.lastname: Kim
authors.forename: Hee Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Jong Kwan
authors.initials: JK
authors.lastname: Park
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
mesh_terms: D000818:Animals; D002460:Cell Line; D034242:Cyclooctanes / Q000302:isolation & purification / Q000494:pharmacology; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D032141:Schisandra; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051899:Smad2 Protein / Q000037:antagonists & inhibitors* / Q000502:physiology; D051900:Smad3 Protein / Q000037:antagonists & inhibitors* / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D034242:Cyclooctanes; D017705:Lignans; D010936:Plant Extracts; D011083:Polycyclic Compounds; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C015499:schizandrin B; D020928:Mitogen-Activated Protein Kinases