Sodium butyrate prevents radiation-induced cognitive impairment by restoring pCREB/BDNF expression

Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages.To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation.Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation.We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor.Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.Sodium butyrate pretreatment reversed these changes.These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No.KIRAMS16-0002)on December 30,2016.

Anti-inflammatory and Anti-oxidative Effects of the Ethanol Extract of Cryptocarya densiflora Blume in Lipopolysaccharide-Stimulated RAW264,7 Mouse Macrophages

CD （Cryptocarya densiflora） Blume has traditionally been used as an herbal medicine. In this study, the effects of CDEE （CD ethanol extract） on inflammation were investigated in LPS （lipopolysaccharide）-stimulated mouse RAW264.7 macrophages. We investigated the effects of CDEE on the production of NO, PGE2 interleukin （IL）-6, IL-1β, and tumor necrosis factor （TNF）-α in LPS-stimulated RAW264.7 cells. We measured the mRNA or protein expression of the pro-inflammatory mediators induced by CDEE in LPS-stimulated RAW264.7 cells. We explored the expression of Nrf-2, heme oxygenase （HO）-I and NADPH-quinone oxidoreductase （NQO）-I to elucidate the antioxidative mechanisms. CDEE significantly inhibited the production of NO, PGE2, IL-6, IL-1β and TNF-α in LPS-stimulated RAW264.7 cells. CDEE suppressed the mRNA or protein expression of iNOS, COX-2, and the MAPKs with a reduction in the translocation of NF-κB in LPS-stimulated RAW264.7 cells. In addition, CDEE significantly increased the expression of HO-I and NQO-1 with an increase in the translocation of Nrf-2 into the nucleus. These results indicate that CDEE inhibits the LPS-induced inflammatory and oxidative responses via suppression of NF-κB activation and the enhancement of Nrf2 activation. We suggest that CDEE may be therapeutic for treating inflammatory diseases.