Inhibitory effects of fermented extract of Ophiopogon japonicas on thrombin-induced vascular smooth muscle cells

Ophiopogon japonicus is known to have various pharmacological effects. The present study investigated the effects of an extract of fermented Ophiopogon japonicas (FEOJ) on thrombin-treated vascular smooth muscle cells. (VSMCs). FEOJ treatment inhibited the proliferation of VSMCs treated with thrombin as indicated by an MTT assay. These inhibitory effects were associated with decreased phosphorylation of AKT, reduced expression of cyclin D1 and increased expression of p27KIP1 in thrombin-induced VSMCs. In addition, FEOJ treatment suppressed the thrombin-stimulated migration of VSMCs as demonstrated by a wound-healing migration assay. Furthermore, zymographic analyses demonstrated that treatment of FEOJ with VSMCs suppressed the thrombin-induced expression of matrix metalloproteinase (MMP)-2, which was attributed to the reduction of nuclear factor (NF)-kappa B binding activity. Collectively, these results demonstrated that FEOJ induced p27KIP1 expression, reduced cyclin D1 expression and AKT phosphorylation, and inhibited MMP-2 expression mediated by downregulation of NF-kappa B binding activity in thrombin-treated VSMCs, which led to growth inhibition and repression of migration. These results supported the use of FEOJ for the prevention of vascular diseases and provided novel insight into the underlying mechanism of action.