title: Aged Garlic Extract Suppresses the Development of Atherosclerosis in Apolipoprotein E-Knockout Mice.
abstract: BACKGROUND
  Aged garlic extract (AGE) has been shown to retard the progression of coronary calcification in patients with coronary artery disease.
  
  
  OBJECTIVE
  To clarify the mechanism of AGE's action to retard atherosclerosis, we investigated whether AGE suppresses the formation and progression of atherosclerosis in Apolipoprotein E (Apoe)-knockout (ApoE-KO) mice.
  
  
  METHODS
  Male C57BL/6J mice (control mice, 5 wk old) were fed a standard diet, whereas male ApoE-KO mice (5 wk old) were fed a standard diet with or without 3% AGE for 12 or 24 wk. After the treatment, blood samples, aortas, and spleens were collected from all mice. Concentrations of total cholesterol (TC), HDL cholesterol, and triglycerides (TGs) in serum were measured. The area of atherosclerotic lesion in the aorta was examined by Oil Red O staining. The relative abundances of monocytes plus macrophages (CD11b(+) cells) and interferon-γ-producing CD4(+) T cells in spleen were assessed by flow cytometric analysis.
  
  
  RESULTS
  The atherosclerotic lesion areas in the aortas of ApoE-KO mice were 87 and 114 times as great (P < 0.01) as those in control mice at 12 and 24 wk, respectively. AGE feeding significantly inhibited the progression of atherosclerotic lesion area in ApoE-KO mice by 22% (P < 0.05) at 12 wk. In addition, serum concentrations of TC and TGs in ApoE-KO mice were significantly higher than those in control mice at 12 and 24 wk. Treatment with AGE significantly suppressed the increases in serum concentrations of TC and TGs in ApoE-KO mice by 21% (P < 0.05) and 19% (P < 0.05) at 24 wk, respectively, and reduced the relative abundance of CD11b(+) cells in ApoE-KO mice by 24% (P < 0.05) at 12 wk.
  
  
  CONCLUSIONS
  These data suggest that the antiatherosclerotic activity of AGE is at least partly due to the suppression of inflammation and lipid deposition in the vessels during the early stage of atherosclerotic development in ApoE-KO mice.
authors.affiliation: Drug Discovery Laboratory and morihara_n@wakunaga.co.jp.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Morihara
authors.affiliation: Healthcare Research and Development Division, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hino
authors.affiliation: Drug Discovery Laboratory and.
authors.forename: Takako
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Drug Discovery Laboratory and.
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D018845:CD11 Antigens / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D018450:Disease Progression; D005737:Garlic; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D013154:Spleen / Q000187:drug effects; D013601:T-Lymphocytes / Q000378:metabolism; D014280:Triglycerides / Q000097:blood*
chemical_list: D001057:Apolipoproteins E; D018845:CD11 Antigens; D018836:Inflammation Mediators; D010936:Plant Extracts; D014280:Triglycerides; D007371:Interferon-gamma; D002784:Cholesterol
keywords: CD11b; T helper cell 1; aged garlic extract; apolipoprotein E–knockout mice; atherosclerosis; cholesterol; triglyceride