The ginsenoside protopanaxatriol protects endothelial cells from hydrogen peroxide-induced cell injury and cell death by modulating intracellular redox status.
Ginsenosides, the active components of the famous Chinese herb ginseng, have been suggested to possess cardiovascular-protective effects. The mechanism of ginsenosides is believed to be associated with their ability to prevent cellular oxidative stress. The purpose of this study was to explore the cytoprotective effects of the ginsenoside protopanaxatriol (PPT) on hydrogen peroxide (H(2)O(2))-induced endothelial cell injury and cell death. Pretreatment of human umbilical vein endothelial cells (HUVECs) with PPT for 24 h was able to protect the cells against H(2)O(2)-induced injury. In addition to cell death, pretreatment with PPT could also reduce H(2)O(2)-induced DNA damage, overactivation of the DNA repair enzyme PARP-1, and concomitant depletion of the intracellular substrate NAD(+). Furthermore, PPT could reverse the decrease in ATP/ADP ratio caused by H(2)O(2). The metabolism of glutathione was also changed. H(2)O(2) could induce a significant decrease in GSH level resulting in a decrease in the GSH/GSSG ratio. This could be prevented by pretreatment with PPT. The action was associated with increasing activities of the GSH-metabolizing enzymes glutathione reductase and glutathione peroxidase. These findings suggest that the ginsenoside PPT could protect HUVECs against H(2)O(2)-induced cell death via its action against oxidative stress, which may be responsible for the cardiovascular-protective action of ginseng.
Kwok
Hoi Hin
HH
Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.
Ng
Wai Yee
WY
Yang
Mildred Sze Ming
MS
Mak
Nai Ki
NK
Wong
Ricky Ngok Shun
RN
Yue
Patrick Ying Kit
PY
D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D005894:Panax / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012502:Sapogenins / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D036145:Ginsenosides; D016877:Oxidants; D012502:Sapogenins; D009243:NAD; C081552:protopanaxatriol; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D011065:Poly(ADP-ribose) Polymerases; D005978:Glutathione; D019803:Glutathione Disulfide