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.