Evodiamine inhibits PDGF-BB-induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress

Vascular smooth muscle cell (VSMC) proliferation is a key event in the development of in-stent restenosis. Evodiamine is an indole alkaloid extracted from the Chinese medicine, evodia, and has been shown to inhibit tumor cell proliferation and protect the cardiovascular system. However, whether evodiamine affects VSMC proliferation remains to be elucidated. Therefore, the present study examined the effects and the mechanisms of action of evodiamine on the proliferation of rat VSMCs. The cells were treated with evodiamine alone or in combination with platelet-derived growth factor-BB (PDGF-BB) stimulation. It was found that evodiamine inhibited PDGF-BB-induced VSMC proliferation in a dose-dependent manner, without inducing cell death. Evodiamine also retarded cell cycle progression, evidenced by the suppression of the expression of cell cycle-promoting cyclin proteins and cyclin-dependent kinases. In addition, evodiamine attenuated the PDGF-BB-induced phosphorylation of mitogen-activated protein kinases p38 and extracellular signal-regulated kinases 1/2, however, it had no effect on the phosphorylation of Akt. Evodiamine also inhibited the increase of reactive oxygen species generation and upregulated the mRNA expression levels of genes encoding antioxidant enzymes. These findings provide important insights into the mechanisms underlying the vasoprotective actions of evodiamine and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease.