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

Abstract

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 plateletderived growth factor (PDGF)-BB-induced rat aortic VSMC proliferation and the possible mechanism of such effects. Pre-treatment of VSMCs with corynoxeine (5-50 m mM) 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 m mM, 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 m mM, 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)g g1 activation or on PDGF receptor beta (PDGF-Rb b) 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.

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1

“…The results of our study showed that Ang II increased phosphorylation of ERK1/2 and stimulated cellular proliferation; in contrast, the ERK inhibitor PD98095 blocked Ang II-induced ERK1/2 phosphorylation and significantly inhibited Ang II-induced HUVSMC proliferation, indicating that ERK1/2 activation works in parallel with HUVSMC proliferation. These results are in line with EI Mabrouk et al and are also supported by another study in which VSMC proliferation induced by PDGF was inhibited by corynoxeine through the blocking of ERK1/2 phosphorylation [21,36] . Therefore, the present data confirm that activation of ERK1/2 plays an important part in HUVSMC proliferation induced by mitogens, such as Ang II.…”

Medicinal uses, phytochemistry and pharmacology of the genus Uncaria

“…other herbs to minimize the conversion of active components (Wu, 1958;. Recently, the aqueous extract of U. rhynchophylla have been reported in the treatment of hypertension, cancer and neurological disorders (epilepsy, Alzheimer's disease, etc) (Fujiwara et al, 2006;Kim et al, 2008;Lee, 2000;Lee et al, 2003;Suk et al, 2002).…”

Vinpocetine Suppresses Pathological Vascular Remodeling by Inhibiting Vascular Smooth Muscle Cell Proliferation and Migration

“…The differential actions on ERK1/2 and AKT have been reported previously. For example, corynoxeine from the Chinese herb (Kim et al, 2008) or knockdown of nonreceptor tyrosine kinase Abl (Jia et al, 2012) attenuated PDGFinduced ERK1/2 phosphorylation but not AKT. In contrast, nitric oxide (Sandirasegarane et al, 2000) as well as bioflavonoids such as tangeretin (Seo et al, 2011), quercetin (Ishizawa et al, 2009), or cudraflavanone (Han et al, 2007), inhibit PGDF-BB-induced SMC proliferation and migration by blocking AKT but not ERK1/2 activation.…”