title: Modulation of NF-κB and FOXOs by baicalein attenuates the radiation-induced inflammatory process in mouse kidney.
abstract: The bioactive flavonoid baicalein has been shown to have radioprotective activity, although the molecular mechanism is poorly understood in vivo. C57BL/6 mice were irradiated with X-rays (15 Gy) with and without baicalein treatment (5 mg/kg/day). Irradiation groups showed an increase of NF-κB-mediated inflammatory factors with oxidative damage and showed inactivation of FOXO and its target genes, catalase and SOD. However, baicalein suppressed radiation-induced inflammatory response by negatively regulating NF-κB and up-regulating FOXO activation and catalase and SOD activities. Furthermore, baicalein inhibited radiation-induced phosphorylation of MAPKs and Akt, which are the upstream kinases of NF-κB and FOXOs. Based on these findings, it is concluded that baicalein has a radioprotective effect against NF-κB-mediated inflammatory response through MAPKs and the Akt pathway, which is accompanied by the protective effects on FOXO and its target genes, catalase and SOD. Thus, these findings provide new insights into the molecular mechanism underlying the radioprotective role of baicalein in mice.
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Jehun
authors.initials: J
authors.lastname: Choi
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Jung
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Sang Woon
authors.initials: SW
authors.lastname: Chung
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism / Q000528:radiation effects; D003404:Creatinine / Q000378:metabolism / Q000528:radiation effects / Q000652:urine; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D044950:Flavanones / Q000494:pharmacology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D009393:Nephritis / Q000378:metabolism* / Q000517:prevention & control*; D051058:Oncogene Protein v-akt / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D010766:Phosphorylation / Q000187:drug effects; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014508:Urea / Q000378:metabolism / Q000528:radiation effects / Q000652:urine; D014965:X-Rays
chemical_list: D000975:Antioxidants; C085126:FOXO1 protein, human; D044950:Flavanones; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D016328:NF-kappa B; D011837:Radiation-Protective Agents; C006680:baicalein; D014508:Urea; D003404:Creatinine; D002374:Catalase; D013482:Superoxide Dismutase; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D005978:Glutathione