20(S)-ginsenoside Rg3 prevents endothelial cell apoptosis via inhibition of a mitochondrial caspase pathway

被引:102
作者
Min, Jeong-Ki
Kim, Jung-Ho
Cho, Young-Lai
Maeng, Yong-Sun
Lee, Shin-Jeong
Pyun, Bo-Jeong
Kim, Young-Myeong
Park, Jeong Hill
Kwon, Young-Guen [1 ]
机构
[1] Yonsei Univ, Coll Sci, Dept Biochem, Seoul, South Korea
[2] Kangwon Natl Univ, Coll Nat Sci, Dept Biochem, Chunchon, Kangwon Do, South Korea
[3] Kangwon Natl Univ, Sch Med, Dept Mol & Cellular Biochem, Chunchon, Kangwon Do, South Korea
[4] Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul, South Korea
关键词
20(S)-ginsenoside Rg3; endothelial cells; apoptosis; Akt; Bad;
D O I
10.1016/j.bbrc.2006.08.129
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ginseng, refering to the roots of the species of the genus Panax ginseng, has been widely used in traditional oriental medicine for its wide spectrum of medicinal effects, such as anti-inflammatory, anti-tumorigenic, adaptogenic, and anti-aging activities. Many of its medicinal effects are attributed to the triterpene glycosides known as ginsenosides. In this study, we report a novel anti-apoptotic activity of 20(S)-ginsenoside Rg3 ((20S)Rg3) and its underlying molecular mechanism in human endothelial cells (ECs). ECs undergo apoptosis associated with increased LEHDase (caspase-9) and DEVDase (caspase-3) activity and DNA fragmentation after 24 h of serum deprivation. These apoptotic markers were suppressed by the addition of (20S)Rg3. (20S)Rg3 increased the expression of Bax and conversely decreased Bcl-2. (20S)Rg3 potently induced a rapid and sustained Akt activation and Bad phosphorylation, resulting in the inhibition of mitochondrial cytochrome c release. These anti-apoptotic activities of (20S)Rg3 were significantly abrogated in cells expressing dominant negative Akt. Taken together, our results suggest that (20S)Rg3 prevents EC apoptosis via Akt-dependent inhibition of the mitochondrial apoptotic signaling pathway. The novel property of (20S)Rg3 may be valuable for developing new pharmaceutical means that will control unwanted endothelial cell death at the site of vascular injury. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:987 / 994
页数:8
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