کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5848476 1130168 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pimaric acid from Aralia cordata has an inhibitory effect on TNF-α-induced MMP-9 production and HASMC migration via down-regulated NF-κB and AP-1
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Pimaric acid from Aralia cordata has an inhibitory effect on TNF-α-induced MMP-9 production and HASMC migration via down-regulated NF-κB and AP-1
چکیده انگلیسی

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)-α. 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)-κB and activator protein-1 transcription factors. A Western-blot analysis using nuclear extract demonstrated that PiMA 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 PiMA. Using the Transwell system, we found that PiMA 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. These results suggest that PiMA has potent anti-atherosclerotic activity with inhibitory action on MMP-9 production and cell migration in TNF-α-induced HASMCs.

► Pimaric acid (PiMA) from Aralia cordata inhibit MMP-9 production and migration of HASMC. ► PiMA inhibit mRNA level and promoter activity of MMP-9. ► PiMA suppress NF-κB p65, c-Fos, p-c-Jun, Jun-D and p-ATF2 proteins in nucleus.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 199, Issue 2, 30 August 2012, Pages 112-119
نویسندگان
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