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Ginsenoside-Rd, a Purified Component From Panax Notoginseng Saponins, Prevents Atherosclerosis in apoE Knockout Mice

Ginsenoside-Rd, a Purified Component From Panax Notoginseng Saponins, Prevents Atherosclerosis in apoE Knockout Mice

Jie Li, Zhi-Zhong Xie, Yong-Bo Tang, Jia-Guo Zhou, Yong-Yuan Guan

Eur J Pharmacol. 2011 Feb 10;652(1-3):104-10.

PMID: 21122802

Abstract:

Recently, it was revealed that the dysfunction of transmembrane Ca(2+) transport, results in an increase in intracellular Ca(2+)[Ca(2+)](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 Ca(2+) 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. Ca(2+) influx was measured by Fura-2 dyed Mn(2+) 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 (20mg/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 Ca(2+) influx in macrophages from high-fat diet apoE(-/-) mice. In vitro, 20μM ginsenoside-Rd significantly inhibited ox-LDL-induced foam cell formation and the increase of thapsigargin- and OAG-induced Ca(2+) 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 Ca(2+) influx through voltage-independent Ca(2+) channels, resulting in the inhibition of SR-A activity and expression, followed by reductions of ox-LDL uptake and cholesterol accumulation in macrophages.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP52705938-A	Ginsenoside Rd		52705-93-8	Price

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