title: Anti-atherosclerotic function of Astragali Radix extract: downregulation of adhesion molecules in vitro and in vivo.
abstract: BACKGROUND
  Atherosclerosis is considered to be a chronic inflammatory disease. Astragali Radix extract (ARE) is one of the major active ingredients extracted from the root of Astragalus membranaceus Bge. Although ARE has an anti-inflammatory function, its anti-atherosclerotic effects and mechanisms have not yet been elucidated.
  
  
  METHODS
  Murine endothelial SVEC4-10 cells were pretreated with different doses of ARE at different times prior to induction with tumor necrosis factor (TNF)-α. Cell adhesion assays were performed using THP-1 cells and assessed by enzyme-linked immunosorbent assay, western blotting and immunofluorescence analyses to detect the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), phosphorylated inhibitor of κB (p-iκB) and nuclear factor (NF)-κB. We also examined the effect of ARE on atherosclerosis in the aortic endothelium of apolipoprotein E-deficient (apoE(-/-)) mice.
  
  
  RESULTS
  TNF-α strongly increased the expression of VCAM-1 and ICAM-1 accompanied by increased expression of p-iκB and NF-κB proteins. However, the expression levels of VCAM-1 and ICAM-1 were reduced by ARE in dose- and time-dependent manners, with the strongest effect at a dose of 120 μg/ml incubated for 4 h. This was accompanied by significantly decreased expression of p-iκB and inhibited activation of NF-κB. Immunofluorescence analysis also revealed that oral administration of ARE resulted in downregulation of adhesion molecules and decreased expression of macrophages in the aortic endothelium of apoE(-/-) mice. ARE could suppress the inflammatory reaction and inhibit the progression of atherosclerotic lesions in apoE(-/-) mice.
  
  
  CONCLUSIONS
  This study demonstrated that ARE might be an effective anti-inflammatory agent for the treatment of atherosclerosis, possibly acting via the decreased expression of adhesion molecules.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: You
authors.forename: Yan
authors.initials: Y
authors.lastname: Duan
authors.forename: Shao-wei
authors.initials: SW
authors.lastname: Liu
authors.forename: Xiao-lin
authors.initials: XL
authors.lastname: Zhang
authors.forename: Xiu-li
authors.initials: XL
authors.lastname: Zhang
authors.forename: Jia-tao
authors.initials: JT
authors.lastname: Feng
authors.forename: Cheng-hui
authors.initials: CH
authors.lastname: Yan
authors.forename: Ya-ling
authors.initials: YL
authors.lastname: Han
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: C543477:Astragali compound; D015815:Cell Adhesion Molecules; D004365:Drugs, Chinese Herbal