title: Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases.
abstract: Ionizing radiation can induce DNA damage and cell death by generating reactive oxygen species (ROS). The objective of this study was to investigate the radioprotective effect of paeoniflorin (PF, a main bioactive component in the traditional Chinese herb peony) on irradiated thymocytes and discover the possible mechanisms of protection. We found 60Co gamma-ray irradiation increased cell death and DNA fragmentation in a dose-dependent manner while increasing intracellular ROS. Pretreatment of thymocytes with PF (50-200 microg/ml) reversed this tendency and attenuated irradiation-induced ROS generation. Hydroxyl-scavenging action of PF in vitro was detected through electron spin resonance assay. Several anti-apoptotic characteristics of PF, including the ability to diminish cytosolic Ca2+ concentration, inhibit caspase-3 activation, and upregulate Bcl-2 and downregulate Bax in 4Gy-irradiated thymocytes were determined. Extracellular regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 kinase were activated by 4Gy irradiation, whereas its activations were partly blocked by pretreatment of cells with PF. The presence of ERK inhibitor PD98059, JNK inhibitor SP600125 and p38 inhibitor SB203580 decreased cell death in 4Gy-irradiated thymocytes. These results suggest PF protects thymocytes against irradiation-induced cell damage by scavenging ROS and attenuating the activation of the mitogen-activated protein kinases.
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Taiping Road 27#, Beijing 100850, People's Republic of China.
authors.forename: Chun Rong
authors.initials: CR
authors.lastname: Li
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.forename: Yu Ning
authors.initials: YN
authors.lastname: Sun
authors.forename: Jin Ming
authors.initials: JM
authors.lastname: Dai
authors.forename: Sheng Qi
authors.initials: SQ
authors.lastname: Wang
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000528:radiation effects; D003037:Cobalt Radioisotopes / Q000633:toxicity; D019610:Cytoprotection / Q000187:drug effects*; D004249:DNA Damage / Q000528:radiation effects; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005720:Gamma Rays; D005960:Glucosides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D039821:Monoterpenes; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D006027:Glycosides
chemical_list: D001565:Benzoates; D001952:Bridged-Ring Compounds; D002118:Calcium; D053148:Caspase 3; D003037:Cobalt Radioisotopes; D005960:Glucosides; D020928:Mitogen-Activated Protein Kinases; D039821:Monoterpenes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; C052617:Bcl2 protein, mouse; C015423:peoniflorin; D006027:Glycosides