title: Role of magnolol in the proliferation of vascular smooth muscle cells.
abstract: BACKGROUND
  Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of vascular remodeling. Recently, magnolol has been reported to have a potential role in regulating tumor necrosis factor α-induced proliferation of VSMCs. However, the role of magnolol in platelet-derived growth factor (PDGF)-induced proliferation of VSMCs remains unknown.
  
  
  OBJECTIVE
  Our purpose was to elucidate the effect of magnolol on the proliferation of VSMCs induced by PDGF-BB and to investigate the underlying molecular mechanisms.
  
  
  RESULTS
  Our data demonstrated that magnolol inhibited rat VSMC proliferation and DNA synthesis stimulated by 20 ng/ml PDGF-BB without causing cell cytotoxicity. Flow cytometric analysis showed that magnolol inhibited S-phase entry of VSMCs. We also demonstrated that magnolol caused this effect by inhibiting the mRNA and protein expression of cyclin D1, cyclin E, and cyclin-dependent kinases 2 and 4 in PDGF-BB-stimulated VSMCs. Further analysis showed that the inhibitory effect of magnolol on the proliferation of VSMCs was associated with the inhibition of the PDGF-BB-stimulated production of intracellular reactive oxygen species (ROS) and Ras, MEK, and ERK1/2 activation.
  
  
  CONCLUSIONS
  These results demonstrate that magnolol can block the proliferation of VSMCs through inhibition of intracellular ROS production and Ras-MEK-ERK1/2 pathways. Magnolol, therefore, has a potential application in preventing atherosclerosis and restenosis.
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Zou
authors.forename: W
authors.initials: W
authors.lastname: Xia
authors.forename: Q
authors.initials: Q
authors.lastname: Dong
authors.forename: L
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017705:Lignans / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001713:Biphenyl Compounds; D017705:Lignans; D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; C005498:magnolol; D000077214:Becaplermin