Pinocembrin Downregulates Vascular Smooth Muscle Cells Proliferation and Migration Leading to Attenuate Neointima...

The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are a primary cause of cardiovascular diseases such as atherosclerosis and restenosis after angioplasty. Pinocembrin (5,7-dihydroxyflavanone, PCB), a natural flavonoid compound found abundantly in propolis, has been reported to have antibacterial, anti-inflammatory, antioxidant, and anticancer effects, and cardiac function improvement in ischemic heart disease. In this study, the protective effects of PCB against the migration and proliferation of VSMCs were investigated. MTT and BrdU assays were performed to estimate the cytotoxicity and cell proliferative activity of PCB, respectively. Rat aortic VSMC migrations and neointima formation were evaluated using wound healing, boyden chamber assays, and in balloon-injured (BI) rat, respectively. PCB suppressed the phosphorylated levels of p38 in PDGF-BB-induced VSMCs followed by reducing the expression of MMP2 and 9. PCB downregulated the expression levels of cell cycle regulatory proteins such as PCNA, CDK2, CDK4, and Cyclin D1. Furthermore, the phosphorylated levels of FAK at Y397 and Y925 sites and the expression levels of FAK-related proteins such as Integrin β1, Paxillin, Talin, and Vinculin were significantly reduced by PCB in PDGF-BB-induced VSMCs. The neointima formation was markedly decreased by PCB administration in the carotid artery of a balloon-injured rat. In conclusion, PCB inhibits the proliferation and migration of VSMCs by stimulation of PDGF-BB through the regulation of the p38 and FAK signaling pathway. Therefore, PCB may be a promising therapeutic candidate for preventing and treating cardiovascular diseases such as atherosclerosis and restenosis.