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    題名: Cinnamophilin reduces oxidative damage and protects against transient focal cerebral ischemia in mice
    作者: Lee, EJ;Chen, HY;Lee, MY;Chen, TY;Hsu, YS;Hu, YL;Chang, GL;Wu, TS
    貢獻者: 藥學院藥學系;Natl Cheng Kung Univ, Dept Chem, Tainan 701, Taiwan;Natl Cheng Kung Univ, Ctr Med, Neurophysiol Lab, Neurosurg Serv,Dept Surg, Tainan, Taiwan;Natl Cheng Kung Univ, Ctr Med, Inst Biomed Engn, Tainan, Taiwan;Sch Med, Tainan, Taiwan;China Med Univ, Inst Pharm, Taichung, Taiwan;Buddhist Tzu Chi Gen Hosp, Dept Anesthesiol, Hualien, Taiwan;Natl Res Inst Chinese Med, Taipei, Taiwan
    日期: 2005
    上傳時間: 2010-09-24 18:56:10 (UTC+8)
    出版者: PERGAMON-ELSEVIER SCIENCE LTD
    摘要: The large amount of nitric oxide (NO) produced by inducible NO synthase (iNOS) contributes to cellular injury in inflammatory disease. In the present study, a novel synthetic compound (3E)-4-(2-hydroxyphenyl)but-3-en-2-one (HPB) was found to inhibit lipopolysaccharide (LPS)-induced NO generation, but not through the inhibition of iNOS activity, in RAW 264.7 macrophages. Administration of HPB into mice also inhibited the LPS-induced increase in serum nitrite/nitrate levels. To evaluate the underlying mechanisms of HPB inhibition of NO generation, the expression of the WOS gene in RAW 264.7 macrophages was examined. HPB abolished the LPS-induced expression of iNOS protein, iNOS mRNA and iNOS promoter activity in a similar concentration-dependent manner. LPS-induced nuclear factor-kappa B (NF-kappa B) DNA binding and NF-kappa B-dependent reporter gene activity were both significantly inhibited by HPB. This effect was mediated through the inhibition of inhibitory factor-KBot (I kappa B alpha) phosphorylation and degradation, and of p65 nuclear translocation. HPB had no effect on the LPS-induced phosphorylation of extracellular signal -regulated kinase (ERK), p38 mitogen-activated protein kinases (MAPK), and c-Jun NH2-terminal kinase (JNK). However, HPB suppressed the LPS-induced intracellular reactive oxygen species (ROS) production. These results indicate that HPB down-regulates WOS gene expression probably through the inhibition of LPS-induced intracellular ROS production, which has been implicated in the activation of NF-kappa B. (c) 2005 Elsevier Inc. All rights reserved.
    關聯: FREE RADICAL BIOLOGY AND MEDICINE 39(4):495-510
    顯示於類別:[藥學系暨碩博士班] 期刊論文

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