Corosolic acid ameliorates atherosclerosis in apolipoprotein E-deficient mice by regulating the nuclear factor-κB signaling pathway and inhibiting monocyte chemoattractant protein-1 expression

Circ J. 2012;76(4):995-1003. doi: 10.1253/circj.cj-11-0344. Epub 2012 Jan 28.

Abstract

Background: Corosolic acid (CRA) is a pentacyclic triterpene acid that has been shown to exhibit an anti-atherosclerotic effect when added to diets of low-density lipoprotein-deficient mice, but the mechanisms are unclear. The purpose of the present study was to investigate the molecular mechanisms by which CRA ameliorates atherosclerosis.

Methods and results: The anti-atherosclerosis effect of CRA in apolipoprotein E-deficient mice fed a Western-type diet was evaluated using atherosclerosis lesion area, serum profiles, gene expression and histological lesions. In vitro, the mechanisms responsible for the anti-inflammatory effect of CRA were investigated on a lipopolysaccharide-induced inflammation model. This model was also used to investigate in detail the effects of CRA on gene expression and nuclear factor (NF)-κB activation. Compared with the control group, the CRA-treated group exhibited a significant decrease in atherosclerotic lesion area, as well as expression of monocyte chemoattractant protein-1 (MCP-1) and CCR2. In vitro studies showed that CRA treatment downregulated the mRNA levels of MCP-1, and inhibited monocyte adhesion and migration, together with suppression of NF-κB signaling pathway.

Conclusions: CRA is capable of ameliorating atherosclerosis in apolipoprotein E-deficient mice by, partly at least, inhibition of NF-κB activity along with decreased MCP-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Aorta / drug effects*
  • Aorta / immunology
  • Aorta / metabolism
  • Aorta / pathology
  • Aortic Diseases / blood
  • Aortic Diseases / genetics
  • Aortic Diseases / immunology
  • Aortic Diseases / pathology
  • Aortic Diseases / prevention & control*
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Atherosclerosis / blood
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Biomarkers / blood
  • Cell Adhesion / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Inflammation Mediators / metabolism
  • Lipids / blood
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism
  • NF-kappa B / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism
  • Signal Transduction / drug effects*
  • Time Factors
  • Triterpenes / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Apolipoproteins E
  • Biomarkers
  • CCL2 protein, human
  • CCR2 protein, human
  • Ccl2 protein, mouse
  • Ccr2 protein, mouse
  • Chemokine CCL2
  • Inflammation Mediators
  • Lipids
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Receptors, CCR2
  • Triterpenes
  • corosolic acid