Carnosic acid prevents the migration of human aortic smooth muscle cells by inhibiting the activation and expression of matrix metalloproteinase-9

Br J Nutr. 2008 Oct;100(4):731-8. doi: 10.1017/S0007114508923710. Epub 2008 Feb 26.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / chemistry
  • Abietanes / pharmacology*
  • Analysis of Variance
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Aorta
  • Atherosclerosis / metabolism
  • Cell Movement / drug effects
  • Cells, Cultured
  • Depression, Chemical
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Gene Expression
  • Humans
  • Matrix Metalloproteinase 9 / analysis
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / enzymology
  • NF-kappa B / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Salvia miltiorrhiza*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Abietanes
  • Antioxidants
  • NF-kappa B
  • Plant Extracts
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 9
  • salvin