Pimaric acid from Aralia cordata has an inhibitory effect on TNF-alpha-induced MMP-9 production and HASMC migration via down-regulated NF-kappa B and AP-1

Title
Pimaric acid from Aralia cordata has an inhibitory effect on TNF-alpha-induced MMP-9 production and HASMC migration via down-regulated NF-kappa B and AP-1
Author(s)
장현욱서석종[서석종]곽충환[곽충환]정태욱[정태욱]박순진지미연박성수[박성수]서창섭[서창섭]손종근장영채[장영채]박영국[박영국]이영춘[이영춘]김철호[김철호]
Keywords
SMOOTH-MUSCLE-CELL; TUMOR-NECROSIS-FACTOR; MATRIX-METALLOPROTEINASE-9 EXPRESSION; MATRIX METALLOPROTEINASES; ARTERIAL INJURY; TISSUE INHIBITORS; IV COLLAGENASE; RAT; ACTIVATION; GROWTH
Issue Date
201208
Publisher
ELSEVIER IRELAND LTD
Citation
CHEMICO-BIOLOGICAL INTERACTIONS, v.199, no.2, pp.112 - 119
Abstract
Many studies have indicated that activation of matrix metalloproteinase (MMP)-9 and smooth muscle cell (SMC) migration are involved in neointimal formation and atherosclerosis. In this study, we revealed that pimaric acid (PiMA) purified from Aralia cordata had an inhibitory effect on MMP-9 production and migration of human aortic smooth muscle cells (HASMCs) induced by tumor necrosis factor (TNF)-alpha. Down-regulated MMP-9 mRNA transcription was detected in PiMA-treated cells using RT-PCR and the luciferase-tagged MMP-9 promoter assay. Results of an electrophoretic mobility shift assay indicated that PiMA-treated HASMCs showed decreased binding activity of nuclear factor (NF)-kappa B and activator protein-1 transcription factors. A Western-blot analysis using nuclear extract demonstrated that PiMA reduced the levels of NF-kappa B p65, c-Fos, p-c-Jun. Jun-D, and p-ATF2 proteins in the nucleus. In addition, TNF-alpha stimulated mitogen activated protein kinase (MAPK) containing extracellular signal regulated kinase 1 and 2, p38, and c-Jun N-terminal kinase was inhibited by PiMA. Using the Transwell system, we found that PiMA inhibited TNF-alpha 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. These results suggest that PiMA has potent anti-atherosclerotic activity with inhibitory action on MMP-9 production and cell migration in TNF-alpha-induced HASMCs. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/27533http://dx.doi.org/10.1016/j.cbi.2012.06.003
ISSN
0009-2797
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약학대학 > 약학부 > Articles
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