title: Ursane triterpenoids inhibit atherosclerosis and xanthoma in LDL receptor knockout mice.
abstract: BACKGROUND
  In order to determine the mechanism of triterpenes, a class of secondary metabolites in plants, in modulating progression of vascular atherosclerotic lesions, we isolated three ursane triterpenoids (euscaphic acid, tormentic acid and 2alpha-hydroxyursolic acid) from aerial part of Salvia miltirrhiza Bge. and fed LDLr(-/-) mice the isolated compounds at a dose of 10 mg/kg p.o. for 24 weeks.
  
  
  METHODS
  The treated mice were raised with a cholesterol-enriched (1.25%) diet. Implying serum and aorta MCP-1 analysis, we found that all mice treated with the compounds exhibited a significant reduction of whole body and vascular inflammation.
  
  
  RESULTS
  The reduction of macrophage cells' number in aortic atherosclerotic lesions suggests that triterpenes treatment results in the development of a more stable plaque phenotype. Analysis of the structure-activity relationships demonstrates that compounds with a beta-orientated hydrogen-bond forming group at C-3 exhibit more potent anti-atherogenic effect than the alpha-counterpart on the development of atherosclerosis and xanthoma. However, the biological activities of the compounds are significantly reduced when they have C-19 hydrogen-bonds.
  
  
  CONCLUSIONS
  These Results suggest that down-regulation of MCP-1 is the main mechanism for antiatherogenic activity of triterpenes and MCP-1 might play important roles in the development of atherosclerosis and xanthoma.
authors.affiliation: Department of Chinese Materia Medica Analysis, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zai
authors.initials: Z
authors.lastname: Chang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D027544:Salvia / Q000737:chemistry; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood; D014315:Triterpenes / Q000494:pharmacology*; D014973:Xanthomatosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C412810:2-hydroxyursolic acid; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D011973:Receptors, LDL; D014280:Triglycerides; D014315:Triterpenes; C007695:euscaphic acid; D002784:Cholesterol