title: Ginsenoside Rd prevents and rescues rat intestinal epithelial cells from irradiation-induced apoptosis.
abstract: Panax ginseng has been shown to have a protective effect for irradiated animals or cells. Ginsenosides are the most active components isolated from ginseng, and ginsenoside Rd has been identified as one of the effective compounds responsible for the pharmaceutical actions of ginseng. In the present study, we studied the molecular mechanisms for the radio-protective action of ginsenoside Rd in rat intestinal epithelial IEC-6 cells. Cells were irradiated with gamma-ray, and apoptosis was examined using Hoechst staining and Western blot analysis. Treatment with ginsenoside Rd before gamma-irradiation inhibited irradiation-induced apoptosis in IEC-6 cells. Administration of Rd after irradiation also inhibited apoptosis in these cells. Irradiation of IEC-6 cells resulted in inactivation of Akt phosphorylation that was abrogated by Rd. On the other hand, irradiation activated phosphorylation of ERK1/2 but did not affect that of p38 MAPK. Inhibition of Akt phosphorylation prevented the reduction of apoptosis by Rd following irradiation. Pretreatment with an inhibitor of the MEK pathway further decreased the number of apoptotic cells. Rd decreased the ratios of Bax/Bcl-2 and Bax/Bcl-xL, the levels of cytochrome c, and the cleaved form of caspase-3 in irradiated IEC-6 cells. Our results suggest that ginsenoside Rd protects and rescues rat intestinal epithelial cells from irradiation-induced apoptosis through a pathway requiring activation of PI3K/Akt, inactivation of MEK, and also inhibition of a mitochondria/caspase pathway.
authors.affiliation: Department of Radiation Emergency Medicine, The Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba-city, Chiba 263-8555, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Tamura
authors.forename: Xing
authors.initials: X
authors.lastname: Cui
authors.forename: Nagako
authors.initials: N
authors.lastname: Sakaguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Akashi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000528:radiation effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D007202:Indicators and Reagents; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011837:Radiation-Protective Agents; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D053148:Caspase 3; D045304:Cytochromes c; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D036145:Ginsenosides; D007202:Indicators and Reagents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011837:Radiation-Protective Agents; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D048051:p38 Mitogen-Activated Protein Kinases; C049863:ginsenoside Rd