Cryptotanshinone from Salvia miltiorrhiza BUNGE has an inhibitory effect on TNF-α-induced matrix metalloproteinase-9 production and HASMC migration via down-regulated NF-κB and AP-1

Matrix metalloproteinases (MMP-9 and MMP-2) production and smooth muscle cell (SMC) migration may play key roles in the phathogenesis of neointima formation and atherosclerosis. Especially inducible MMP-9 expression was directly involved in the cancer cell invasion and SMC migration through vascular wall. In this study, we reveal that cryptotanshinone (CT) purified from Salvia miltiorrhiza BUNGE had an inhibitory effect on MMP-9 production and migration of human aortic smooth muscle cells treated with TNF-alpha in a dose-dependent manner. The down regulation of transcription of MMP-9 mRNA was evidenced by RT-PCR and MMP-9 promoter assay using luciferase reporter gene. Eletrophoretic mobility shift assay showed NF-kappa B and AP-1 nuclear translocations were suppressed. In addition, Western blot analysis indicated that extracellular signal regulated kinase 1 and 2, p38 and JNK MAP kinase signaling pathways were inhibited. From the results, it is suggested that CT has anti- atherosclerosis and anti-neointimal formation activity. (c) 2006 Elsevier Inc. All rights reserved.