Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

Abstract

Vascular smooth muscle cell (SMC) proliferation plays an important role in the pathogenesis of atherosclerosis and post-angioplasty restenosis. Berberine is a well-known component of the Chinese herb medicine Huanglian (Coptis chinensis), and is capable of inhibiting SMC contraction and proliferation, yet the exact mechanism is unknown. We therefore investigated the effect of berberine on SMC growth after mechanic injury in vitro. DNA synthesis and cell proliferation assay were performed to show that berberine inhibited serum-stimulated rat aortic SMC growth in a concentration-dependent manner. Mechanical injury with sterile pipette tip stimulated the regrowth of SMCs. Treatment with berberine prevented the regrowth and migration of SMCs into the denuded trauma zone. Western blot analysis showed that activation of the MEK1/2 (mitogen-activated protein kinase kinase 1/2), extracellular signal-regulated kinase (ERK), and up-regulation of early growth response gene (Egr-1), c-Fos and Cyclin D1 were observed sequentially after mechanic injury in vitro. Semi-quantitative reverse-transcription PCR assay further confirmed the increase of Egr-1, cFos, platelet-derived growth factor (PDGF) and Cyclin D1 expression in a transcriptional level. However, berberine significantly attenuated MEK/ERK activation and downstream target (Egr-1, cFos, Cyclin D1 and PDGF-A) expression after mechanic injury in vitro. Our study showed that berberine blocked injury-induced SMC regrowth by inactivation of ERK/Egr-1 signaling pathway thereby preventing early signaling induced by injury in vitro. The anti-proliferative properties of berberine may be useful in treating disorders due to inappropriate SMC growth.

Berberine suppresses neuroinflammatory responses through AMP‐activated protein kinase activation in BV‐2 microglia

“…However, berberine has also been reported to have a lipid lowering effect by stabilizing hepatic LDL receptor mRNA in an ERK-dependent manner rather than promoting transcriptional activity [Abidi et al, 2005]. Moreover, it is also reported that berberine suppresses MEK/ERK-dependent signaling pathway to inhibit vascular smooth muscle cell regrowth [Liang et al, 2006]. Here, we find that berberine represses the phosphorylation of ERK signal induced by LPS and IFN-g. We also observed that an inhibitory effect of berberine on ERK Fig.…”

PDGF-dependent regulation of regulator of G protein signaling-5 expression and vascular smooth muscle cell functionality

“…ANG II has been shown to activate multiple signaling pathways (74,84). Importantly, phosphorylation of mitogen-activated protein kinases (MAPKs) has been implicated in the contractile, mitogenic, and trophic responses of arterial VSMCs (16,42,44,47,67,86). Therefore, to determine whether RGS5 expression regulates ANG Fig.…”

Berberine chloride can ameliorate the spatial memory impairment and increase the expression of interleukin-1beta and inducible nitric oxide synthase in the rat model of Alzheimer's disease

“…Berberine could improve quality of life and decrease ventricular premature complexes and mortality in patients with chronic congestive heart failure [16]. Berberine has potential in the prevention of atherosclerosis and restenosis [17,18]. Berberine can block transient outward potassium current ( IA ) and delayed rectifier potassium current ( IK ) in a concentration-dependent manner in acutely isolated CA1 pyramidal neurons of rat hippocampus [19].…”