title: Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation.
abstract: BACKGROUND
  Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration.
  
  
  METHODS
  The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury.
  
  
  RESULTS
  VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity.
  
  
  CONCLUSIONS
  Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation.
  
  
  CONCLUSIONS
  This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis.
authors.affiliation: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, USA; Department of Oriental Medicine Resources, Mokpo National University, South Korea.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Karki
authors.forename: Seong-Bin
authors.initials: SB
authors.lastname: Kim
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058426:Neointima / Q000188:drug therapy* / Q000517:prevention & control; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D001713:Biphenyl Compounds; D017705:Lignans; C005498:magnolol
keywords: Magnolol; Restenosis; Stress fibers; VSMC migration