| Abstract: | 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)-alpha. 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 kappaB (p-ikappaB) and nuclear factor (NF)-kappaB. We also examined the effect of ARE on atherosclerosis in the aortic endothelium of apolipoprotein E-deficient (apoE-/-) mice. RESULTS: TNF-alpha strongly increased the expression of VCAM-1 and ICAM-1 accompanied by increased expression of p-ikappaB and NF-kappaB 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 mug/ml incubated for 4 h. This was accompanied by significantly decreased expression of p-ikappaB and inhibited activation of NF-kappaB. 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. CONCLUSION: 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. |
