Ellagic acid suppresses oxidised low-density lipoprotein-induced aortic smooth muscle cell proliferation: studies on the activation of extracellular signal-regulated kinase 1/2 and proliferating cell nuclear antigen expression

Br J Nutr. 2008 Apr;99(4):709-14. doi: 10.1017/S0007114507831734. Epub 2008 Jan 10.


Proliferation of intimal vascular smooth muscle cells is an important component in the development of atherosclerosis. Ellagic acid is a phenolic compound present in fruits (raspberries, blueberries, strawberries) and walnuts. The present study investigated the effect of ellagic acid on the oxidised LDL (ox-LDL)-induced proliferation of rat aortic smooth muscle cells (RASMC). The study found that ellagic acid significantly inhibited ox-LDL-induced proliferation of RASMC and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Furthermore, ellagic acid also blocked the ox-LDL-induced (inducible) cell-cycle progression and down regulation of the expression of proliferating cell nuclear antigen (PCNA) in RASMC. Therefore, ellagic acid reduced the amount of ox-LDL-induced proliferation of RASMC via inactivation of the ERK pathway and suppression of PCNA expression. These results may significantly advance the understanding of the role that antioxidants play in the prevention of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Aorta
  • Biomarkers / analysis
  • Blotting, Western / methods
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Ellagic Acid / pharmacology*
  • Enzyme Activation / drug effects
  • Flow Cytometry
  • Humans
  • Lipoproteins, LDL / metabolism
  • Lipoproteins, LDL / pharmacology
  • Mitogen-Activated Protein Kinase 3 / analysis
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism*
  • Phosphorylation
  • Proliferating Cell Nuclear Antigen / analysis
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Rats


  • Antioxidants
  • Biomarkers
  • Lipoproteins, LDL
  • Proliferating Cell Nuclear Antigen
  • oxidized low density lipoprotein
  • Ellagic Acid
  • Mitogen-Activated Protein Kinase 3