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Abstract
The proliferation of vascular smooth muscle cells may perform a crucial role in the pathogenesis of vascular dysfunction such as atherosclerosis. The principal objective of this study was to determine the inhibitory effects of ethanol extract from Zanthoxylum schinifolium (EZS) on human aortic smooth muscle cell (HASMC) proliferation induced by TNF-α. The invasion and migration of HASMC was significantly promoted by treatment with TNF-α as compared with control. However, EZS inhibited the TNF-α-induced invasion and migration in a dose-dependent manner (p < 0.01). [3H]-thymidine incorporation was also significantly inhibited by EZS treatment. We utilized western blotting analysis to evaluate the effects of EZS on cell cycle regulatory proteins. TNF-α induced the expression of CDK2/CDK4, and reduced the expression of p21waf1/cip1/p27kip1. However, EZS also attenuated the expression of TNF-α-induced cell cycle regulatory proteins. The results of gelatin zymography demonstrated that the TNF-α-treated HASMC secreted gelatinases, probably including MMP-9, which may be involved in the invasion and migration of HASMC. EZS inhibited the production of TNF-α-induced formation of DCF-sensitive intracellular reactive oxygen species (ROS). Our results showed that EZS exerts inhibitory effects on TNF-α-induced HASMC proliferation and migration, including the inhibition of MMP-9 activity and the down-regulation of ROS/production, thereby suggesting that EZS may be a possible therapeutic approach to the inhibition of atherosclerosis.