Carnosic acid prevents the migration of human aortic smooth muscle cells by inhibiting the activation and expression of matrix metalloproteinase-9.
The migration and matrix metalloproteinase (MMP) activation of vascular smooth muscle cells may play key roles in the development of atherosclerosis. Carnosic acid (CA) is a phenolic compound found in herbs, including rosemary and sage. Previous studies indicated that CA possesses antioxidant activity in vitro. In this study, we investigated the effects of CA on TNF-alpha-induced cell migration, the formation of intracellular reactive oxygen species, the translocation of NF-kappaB and the activation and expression of MMP-9 in human aortic smooth muscle cells (HASMC). The Matrigel migration assay showed that CA (10 and 20 micromol/l) effectively inhibited TNF-alpha-induced migration of HASMC as compared with the control group. To explain this inhibitory effect, MMP-9 was assayed by gelatin zymography and Western blot. The results indicated that CA inhibited MMP-9 activity and expression. Furthermore, the production of reactive oxygen species and the nuclear translocation of NF-kappaB p50 and p65 induced by TNF-alpha were dose-dependently suppressed by CA pretreament. These results indicate that CA has anti-inflammatory properties and may prevent the migration of HASMC by suppressing MMP-9 expression through down-regulation of NF-kappaB.
Yu
Ya-Mei
YM
Department of Health Science, Chang Jung Christian University, 396 Chang Jung Rd., Sec. 1, Kway Jen, Tainan 71101, Taiwan. yuyamei@hotmail.com
Lin
Hsing-Chun
HC
Chang
Weng-Cheng
WC
D045784:Abietanes / Q000737:chemistry / Q000494:pharmacology*; D000704:Analysis of Variance; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001011:Aorta; D050197:Atherosclerosis / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D045784:Abietanes; D000975:Antioxidants; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; C018381:salvin