Inhibitory effect of Cho-Deung-San on human aortic smooth muscle cell migration induced by TNF-α through inhibition of matrix metalloproteinase-2 and -9 activity

The migration and matrix metalloproteinases (MMPs) production of vascular smooth muscle cells (VSMC) may play a key role in the development of atherosclerosis. A Korean traditional herbal formulation, Cho-Deung-San (CDS), which is composed of 11 herbal ingredients, has been used to treat vascular diseases for many centuries. In this study, we investigated the inhibitory effect of CDS on tumor necrosis factor-α (TNF-α)-induced human aortic smooth muscle cells (HASMC) migration and MMP-2 and -9 activity. The cytotoxocity of CDS on HASMC was very low (IC₅₀>500 μg/ml) as measured by the XTT assay method. The Matrigel migration assay showed that CDS effectively inhibited the TNF-α-induced migration of HASMC as compared with the control group in a dose-dependent manner (IC₅₀=85 μg/ml). To explain this inhibitory effect, the extracts prepared from CDS and its herbal ingredients were assayed for gelatin zymography. The results showed that CDS inhibited MMP-2 and -9 activity (IC₅₀=180 and 75 μg/ml, respectively). Among the herbal ingredients of CDS, the hooks and stems of Uncaria sinensis (Oliv.) Havil (UR) has shown significant inhibition against MMP-2 and -9 activity. In addition, the inhibitory effect of UR against gelatinolytic activity of MMP-2 and -9 was higher than that of catechin and lower than that of epigallocatechin gallate. These results suggest that CDS could be used as potential antiatherosclerotic agent, and UR is major component of CDS for antimigration in TNF-α treated HASMC.