title: Corosolic acid ameliorates atherosclerosis in apolipoprotein E-deficient mice by regulating the nuclear factor-κB signaling pathway and inhibiting monocyte chemoattractant protein-1 expression.
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.
  
  
  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.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D015415:Biomarkers; C111835:CCL2 protein, human; C515334:CCR2 protein, human; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D008055:Lipids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D054390:Receptors, CCR2; D014315:Triterpenes; C113861:corosolic acid