Ginsenoside-Rd, a purified component from panax notoginseng saponins, prevents atherosclerosis in apoE knockout mice

Recently, it was revealed that the dysfunction of transmembrane Ca2+ transport, results in an increase in intracellular Ca2+[Ca2+]i, which is involved in the process of atherosclerosis. We previously demonstrated that ginsenoside-Rd, a purified component from panax notoginseng, is a voltage-independent Ca2+ channels blocker. In this study, we investigated the effects of ginsenoside-Rd on atherosclerosis and the underlying mechanisms in apolipoprotein E deficient (apoE−/−) mice and RAW264.7 cells. Atherosclerotic plaques were stained by Red oil O staining. Ca2+ influx was measured by Fura-2 dyed Mn2+ quenching. Intracellular cholesterol and uptake of lipid was assayed by enzymatic, fluorometric method and DiI-labeled Ox-LDL. Western blot was used to determine protein expression. We found that Ginsenoside-Rd (20 mg/kg/day. i.p.) significantly reduced the atherosclerotic plaque areas, oxidized low-density lipoprotein (ox-LDL) uptake and thapsigargin and l-oleoyl-2-acetyl-glycerol (OAG, membrane-permeable diacylglycerol analog)-induced Ca2+ influx in macrophages from high-fat diet apoE−/− mice. In vitro, 20 μM ginsenoside-Rd significantly inhibited ox-LDL-induced foam cell formation and the increase of thapsigargin- and OAG-induced Ca2+ influx. Ox-LDL induced an increase in scavenger receptor A (SR-A) expression, and ginsenoside-Rd inhibited this effect of ox-LDL significantly. The results suggest that ginsenoside-Rd prevents the development of atherosclerosis. The underlying mechanism may be related to the inhibition of Ca2+ influx through voltage-independent Ca2+ channels, resulting in the inhibition of SR-A activity and expression, followed by reductions of ox-LDL uptake and cholesterol accumulation in macrophages.