Corynoxeine isolated from the hook of Uncaria rhynchophylla inhibits rat aortic vascular smooth muscle cell proliferation through the blocking of extracellular signal regulated kinase 1/2 phosphorylation.
The proliferation of vascular smooth muscle cells (VSMCs) induced by injury to the intima of arteries is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis. Uncaria rhynchophylla is traditional Chinese herb that has been applied to the treatment of convulsive disorders, such as epilepsy, in China. In the present study, we examined whether corynoxeine exerts inhibitory effects on platelet-derived growth factor (PDGF)-BB-induced rat aortic VSMC proliferation and the possible mechanism of such effects. Pre-treatment of VSMCs with corynoxeine (5-50 microM) for 24 h resulted in significant decreases in cell number without any cytotoxicity; the inhibition percentages were 25.0+/-12.5, 63.0+/-27.5 and 88.0+/-12.5% at 5, 20 and 50 microM, respectively. Also, corynoxeine significantly inhibited the 50 ng/ml PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without any cytotoxicity; the inhibitions were 32.8+/-11.0, 51.8+/-8.0 and 76.9+/-7.4% at concentrations of 5, 20 and 50 microM, respectively. Pre-incubation of VSMCs with corynoxeine significantly inhibited PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, whereas corynoxeine had no effects on mitogen-activated protein kinase (MAPK/ERK)-activating kinase 1 and 2 (MEK1/2), Akt, or phospholipase C (PLC)gamma1 activation or on PDGF receptor beta (PDGF-Rbeta) phosphorylation. These results suggest that corynoxeine is a potent ERK1/2 inhibitor of key PDGF-BB-induced VSMC proliferation and may be useful in the prevention and treatment of vascular diseases and restenosis after angioplasty.
Kim
Tack-Joong
TJ
Division of Biological Science and Technology, Institute of Biomaterials, Yonsei University, Wonju, Korea.
Lee
Ju-Hyun
JH
Lee
Jung-Jin
JJ
Yu
Ji-Yeon
JY
Hwang
Bang-Yeon
BY
Ye
Sang-Kyu
SK
Shujuan
Li
L
Gao
Li
L
Pyo
Myoung-Yun
MY
Yun
Yeo-Pyo
YP
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D026121:Indole Alkaloids; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D035261:Plant Components, Aerial / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D032070:Uncaria / Q000737:chemistry*
D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D026121:Indole Alkaloids; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C054799:corynoxeine; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3