Nelumbo nucifera leaf extract inhibits neointimal hyperplasia through modulation of smooth muscle cell proliferation and migration.

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. CONCLUSION: 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."

Magnoliae Cortex inhibits intimal thickening of carotid artery through modulation of proliferation and migration of vascular smooth muscle cells.

Endovascular injury leads to proliferation and migration of vascular smooth muscle cells from the media to the intima leading to the intimal thickening. The objective of this study was to examine the effect of Magnoliae Cortex extract (MOE) on intimal thickening of rat carotid artery injured by balloon endothelial denudation. MOE was administered orally using gastric sonde at three different doses MOE200 (200 mg/kg), MOE400 (400 mg/kg), and MOE800 (800 mg/kg) for 14 days from the day of balloon injury. Also, in vitro assays of proliferation, migration and expression of matrix metalloproteinase-2 (MMP-2) in human aortic smooth muscle cells (HASMCs) were carried out using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, transwell boyden chamber method and gelatin zymography, respectively. Oral administration of MOE400 and MOE800 for 14 days significantly inhibited intimal area, intimal/medial ratio (I/M), stenosis rate, expression of proliferating cell nuclear antigen (PCNA), MMP-2, and -9 in denudated rat carotid artery. Our in vitro assays revealed that MOE dose dependently inhibited proliferation, migration and expression of MMP-2 in HASMCs. Thus, the results suggest that MOE can be considered as a therapeutic value in the prevention of atherosclerosis because restenosis after percutaneous transluminal coronary angioplasty (PTCA) is supposed to be 'accelerated atherosclerosis'.

Chungtaejeon, a Korean fermented tea, scavenges oxidation and inhibits cytokine induced proliferation and migration of human aortic smooth muscle cells.

Oxidation susceptibility of serum lipid and the proliferation and migration of vascular smooth muscle cells (VSMC) from tunica media to the sub endothelial region are the key steps in the progression of atherosclerosis. The objective of this study was to determine the effects of Chungtaejeon (CTJ) on oxidation and cytokine induced proliferation and migration of human aortic smooth muscle cells (HASMC). The antioxidative effects of CTJ were evaluated by using 1,1-diphenyl-2-picryl hydrazyl (DPPH) scavenging assay, nitric oxide (NO) scavenging assay and thiobarbituric acid reactive substance (TBARS) assay. Similarly, the proliferation, migration and expression of matrix metalloproteinases (MMPs) in HASMC were assessed by MTT assay, transwell Boyden chamber assay and gelatin zymography, respectively. Western blotting was done to determine the protein expression of MMP-9, phospho extracellular regulated kinase (pERK1/2) and phospho c-Jun N-terminal kinase (pJNK). In results, the IC(50) values for DPPH and NO scavenging activities were 8.91 µg/ml and 14.32 µg/ml, respectively. Furthermore, CTJ inhibited TBARS formation dose dependently. The pretreatment of CTJ dose dependently inhibited the tumor necrosis factor-α (TNF-α) induced proliferation and MMP-9 expression and platelet derived growth factor (PDGF) induced migration of HASMC. Thus, CTJ can be suggested to have beneficial effect in the prevention of atherosclerosis.