Pimaric acid has potent anti-atherosclerotic activity with inhibitory action on matrix metalloproteinase-9 production and cell migration in TNF-α±-induced human aortic smooth muscle cells.

Down-regulated MMP-9 mRNA transcription was detected in Pimaric acid-treated cells using RT-PCR and the luciferase-tagged MMP-9 promoter assay. Results of an electrophoretic mobility shift assay indicated that Pimaric acid-treated HASMCs showed decreased binding activity of nuclear factor (NF)-κB and activator protein-1 transcription factors. A Western-blot analysis using nuclear extract demonstrated that Pimaric acid reduced the levels of NF-κB p65, c-Fos, p-c-Jun, Jun-D, and p-ATF2 proteins in the nucleus. In addition, TNF-α± stimulated mitogen activated protein kinase (MAPK) containing extracellular signal regulated kinase 1 and 2, p38, and c-Jun N-terminal kinase was inhibited by Pimaric acid. Using the Transwell system, we found that Pimaric acid inhibited TNF-α± stimulated HASMC migration/invasion in a dose-dependent manner. To confirm whether MAPK mediated MMP-9 expression, we used MAPK inhibitors including U0126, SB253580, and SP600125 and found that those inhibitors reduced MMP-9 expression and HASMC migration/invasion[1]