Ginsenoside-Rd, a purified component from panax notoginseng saponins, prevents atherosclerosis in apoE knockout mice.
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.
Department of Pharmacology, Zhongshan School of Medicine, and Vascular Research Center, Sun Yat-Sen University, Guangzhou 510089, People's Republic of China.
Jie
J
Li
Zhi-Zhong
ZZ
Xie
Yong-Bo
YB
Tang
Jia-Guo
JG
Zhou
Yong-Yuan
YY
Guan
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015220:Calcium Channels / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D036145:Ginsenosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053723:Panax notoginseng / Q000378:metabolism*; D012503:Saponins / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D001057:Apolipoproteins E; D015220:Calcium Channels; D036145:Ginsenosides; D012503:Saponins; D014280:Triglycerides; D002784:Cholesterol; C049863:ginsenoside Rd