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Astragaloside IV (AsIV) is the major effective component extracted from the Chinese herb Astragalus membranaceus, which has been widely used to treat cardiovascular disease. Recent studies have shown that AsIV can potentially protect the arteries from atherosclerosis; however the mechanisms underneath are unknown. The aim of this study was to investigate the effects of AsIV on blood lipids, CD40-CD40L signal system, and SDF-1/CXCR4 biological axis in high-fat diet apoE−/− mice and reveal the molecular mechanisms of AsIV against atherosclerosis. Here, we showed that AsIV alleviated the extent of atherosclerosis in aorta of apoE−/− mice. And AsIV can significantly downregulate PAC-1, CD40L, and CXCR4 expression on platelet surface in blood of high-fat diet apoE−/− mice. AsIV also can significantly downregulate mRNA and protein level of SDF-1 and CXCR4 in thoracic aorta. Consistent with aorta CXCR4 expression, CXCR4 in bone marrow-derived endothelial progenitor cell (EPC) was also reduced. Meanwhile biochemical analysis showed that AsIV could downregulate TG, TC, and LDL-C levels and upregulate HDL-C level in blood of high-fat diet apoE−/− mice. We concluded that the protective effects of AsIV in atherosclerosis injury may be related to regulating blood lipids, CD40-CD40L system, and SDF-1/CXCR4 biological axis. SDF-1/CXCR4 biological axis is probably one of the main targets of intervening atherosclerosis.

Effects of Astragaloside IV on the SDF-1/CXCR4 Expression in Atherosclerosis of apoE−/− Mice Induced by Hyperlipaemia