title: Inhibitory effect of the combination therapy of simvastatin and pinocembrin on atherosclerosis in ApoE-deficient mice.
abstract: The present study was performed to investigate the effects of the combination therapy of pinocembrin and simvastatin on the atherosclerotic lesions development in the ApoE-/- mice.
  
  
  METHODS
  Eight-week-old male ApoE-/- mice were fed high fat diet (HFD) and treated with simvastatin (10 mg/kg per day), pinocembrin (20 mg/kg per day), or the combination therapy (simvastatin 5 mg/kg per day and pinocembrin 20 mg/kg per day) for 14 weeks. The serum lipid levels, nitric oxide (NO), endothelin (ET), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined with spectrophotometric measurement and ELISA assay. Vascular endothelial growth factor (VEGF) in serum and aortic root was detected. En face analyses of atherosclerotic lesion in whole aorta and aortic root sections were performed with plaque staining using oil red O.
  
  
  RESULTS
  The combination treatment with simvastatin and pinocembrin resulted in significantly decreased levels of serum total cholesterol, triglycerides and low-density lipoprotein cholesterol, augmented NO levels and SOD activity, inhibited ET and VEGF expression. Immunohistochemistry of aortic valve sections revealed that the combination therapy also suppressed the expression of VEGF induced by HFD. In addition, HFD-induced arterial wall lipid disposition displayed by oil red O staining was reduced significantly in aortic root and whole aorta en face in the combination administrated mice. The effect of the combination was superior to simvastatin alone.
  
  
  CONCLUSIONS
  The combination of simvastatin and pinocembrin synergistically inhibited atherosclerotic lesion development in ApoE-/- mice with hyperlipidemia, which is partially dependent on the protective of vascular endothelium.
authors.affiliation: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, Taishan Medical University, Taian 271000, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sang
authors.forename: Na
authors.initials: N
authors.lastname: Yuan
authors.forename: Shutong
authors.initials: S
authors.lastname: Yao
authors.forename: Furong
authors.initials: F
authors.lastname: Li
authors.forename: Jiafu
authors.initials: J
authors.lastname: Wang
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Fang
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy / Q000235:genetics; D059305:Diet, High-Fat; D004338:Drug Combinations; D016232:Endothelins / Q000097:blood; D044950:Flavanones / Q000008:administration & dosage*; D006801:Humans; D008055:Lipids / Q000097:blood; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D009569:Nitric Oxide / Q000097:blood; D019821:Simvastatin / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D004338:Drug Combinations; D016232:Endothelins; D044950:Flavanones; D008055:Lipids; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D008315:Malondialdehyde; C016063:pinocembrin; D019821:Simvastatin; D013482:Superoxide Dismutase