20(S)-Ginsenoside Rg3 prevents endothelial cell apoptosis via inhibition of a mitochondrial caspase pathway.
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 24h 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.
Min
Jeong-Ki
JK
Department of Biochemistry, College of Sciences, Yonsei University, Seoul, Republic of Korea.
Kim
Jung-Ho
JH
Cho
Young-Lai
YL
Maeng
Yong-Sun
YS
Lee
Shin-Jeong
SJ
Pyun
Bo-Jeong
BJ
Kim
Young-Myeong
YM
Park
Jeong Hill
JH
Kwon
Young-Guen
YG
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology*; D015394:Molecular Structure; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000145:classification / Q000235:genetics; D051025:bcl-Associated Death Protein / Q000378:metabolism
D016895:Culture Media, Serum-Free; D036145:Ginsenosides; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; C097367:ginsenoside Rg3; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases