title: Nelumbo nucifera leaf extract inhibits neointimal hyperplasia through modulation of smooth muscle cell proliferation and migration.
abstract: OBJECTIVE
  Endovascular injury induced by balloon withdrawal leads to the increased activation of matrix metalloproteinases (MMPs) in the vascular wall allowing the proliferated smooth muscle cells (SMCs) to digest the surrounding extracellular matrix and migrate from the media into the intima leading to the intimal thickening. The objective of this study was to examine the effect of Nelumbo nucifera leaf extract (NL) on intimal thickening of rat carotid artery injured by balloon catheter and on the proliferation and migration of cultured vascular smooth muscle cells (VSMCs) induced by tumor necrosis factor-α.
  
  
  METHODS
  NL was administered orally using gastric sonde at three different doses, 100 mg kg(-1) (NL100), 400 mg kg(-1) (NL400), and 800 mg kg(-1) (NL800) for 4 wk from the day of balloon injury in the rats. VSMC proliferation and migration were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Boyden chamber methods, whereas enzymatic action of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) was carried out by gelatin zymography, and MMP-9 protein expression, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase phosphorylations were assessed by Western blot analyses.
  
  
  RESULTS
  NL reduced the intimal thickening by suppressing VSMC's proliferation through inhibition of extracellular signal-regulated kinase 1/2 phosphorylation and their migration by reducing the expression of MMP-2 and -9 through inhibition of JNK1/2 phosphorylation.
  
  
  CONCLUSIONS
  Thus, the results suggest that NL can be considered of therapeutic value in the prevention of atherosclerosis because restenosis after percutaneous transluminal coronary angioplasty can be considered a model of "accelerated atherosclerosis."
authors.affiliation: Department of Oriental Medicine Resources, Mokpo National University, 61 Muan-gun, Jeonnam 534-729, South Korea.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Karki
authors.forename: Eun-Raye
authors.initials: ER
authors.lastname: Jeon
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006965:Hyperplasia; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D031653:Nelumbo / Q000737:chemistry*; D058426:Neointima / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats
chemical_list: D010936:Plant Extracts; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat