Abstract
BACKGROUND: The migration of vascular smooth muscle cells from the tunica media to the subendothelial region may be a key event in the development of atherosclerosis after arterial injury. In this study, we investigated the potential mechanisms underlying the anti-atherosclerotic effects of Schisandrae Semen essential oil (SSeo) in human aortic smooth muscle cells (HASMCs). METHODS: Metalloproteinase-2/9 (MMP-2/9) activity was evaluated by gelatin zymography and gelatinase activity assay kit. The possible mechanisms underlying SSeo-mediated reduction of by tumor necrosis factor (TNF)-α-induced cell invasion and inhibition of secreted and cytosolic MMP-9 production in HASMCs were investigated. RESULTS: Our results indicate that SSeo treatment has an inhibitory effect on activation as well as expression of MMP-9 induced by TNF-α in HASMCs in a dose-dependent manner without significant cytotoxicity. SSeo attenuated nuclear translocation of TNF-α-mediated nuclear factor-kappa B (NF-κB) and blocked degradation of the NF-κB inhibitor proteins as well as the production of reactive oxygen species. SSeo also reduced TNF-α-induced production of pro-inflammatory mediators such as nitric oxide and prostaglandin E2 and inhibited inducible nitric oxide synthase and cyclooxygenase-2 expression in HASMCs. Furthermore, the Matrigel migration assay showed that SSeo effectively reduced TNF-α-induced HASMC migration compared with that in the control group. CONCLUSIONS: Taken together, these results suggest that SSeo treatment suppresses TNF-α-induced HASMC migration by selectively inhibiting MMP-9 expression, which was associated with suppression of the NF-κB signaling pathway. Taken together, these results suggest that SSeo has putative potential anti-atherosclerotic activity.