https://scholars.lib.ntu.edu.tw/handle/123456789/380880
標題: | The therapeutic potential and mechanisms of action of quercetin in relation to lipopolysaccharide-induced sepsis in vitro and in vivo | 作者: | Chang, Y.-C. Tsai, M.-H. Sheu, W.H.-H. SHU-CHEN HSIEH Chiang, A.-N. |
公開日期: | 2013 | 卷: | 8 | 期: | 11 | 來源出版物: | PLoS ONE | 摘要: | Sepsis caused by Gram-negative bacterial infection is characterized by extensive inflammatory cytokine production, which leads to multiple organ failure and a high lethality rate. Therefore, compounds that are able to alleviate profound inflammatory responses may have therapeutic potential in relation to sepsis. Quercetin, one of the flavonoids found widely in the human diet, has been reported to have many health benefits, but the mechanisms underlying its biological effects remain obscure. In the present study, our aim was to investigate the molecular mechanisms by which quercetin inhibits lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and to evaluate the capacity of quercetin to attenuate the mortality rate in a mice model of lethal sepsis. Our results show that quercetin significantly attenuates LPS-induced production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1α) in RAW264.7 macrophages. The LPS-stimulated phosphorylations of the inhibitors of κB kinase (IKKs), Akt, and c-Jun N-terminal kinase (JNK) are also inhibited by quercetin. Quercetin causes a significant reduction in the phosphorylation and degradation of inhibitor of κBα (IκBα) and in the nuclear level of nuclear factor-κB (NF-κB), the latter being associated with decreased NF-κB binding activity. Most importantly, acute administration of quercetin reduces the lethality rate and circulating levels of TNF-α and IL-1β in C57BL/6J mice with endotoxemia induced by LPS, whereas chronic dietary supplementation with quercetin shows no inhibitory effect on serum TNF-α and IL-1β levels. These findings provide clues that quercetin may be a promising agent for the prevention of systemic inflammatory diseases such as sepsis. ? 2013 Chang et al. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84896712417&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/380880 |
DOI: | 10.1371/journal.pone.0080744 | SDG/關鍵字: | bacterium lipopolysaccharide; I kappa B kinase alpha; immunoglobulin enhancer binding protein; interleukin 1beta; protein kinase B; quercetin; stress activated protein kinase; tumor necrosis factor alpha; animal cell; animal experiment; animal model; animal tissue; antiinflammatory activity; article; controlled study; cytokine production; dose response; drug protein binding; endotoxemia; in vitro study; in vivo study; inflammation; intracellular signaling; lethality; macrophage; male; mouse; nonhuman; protein phosphorylation; sepsis; treatment outcome; Animals; Cell Line; Disease Models, Animal; Enzyme Activation; I-kappa B Kinase; Interleukin-1beta; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Macrophages; Male; Mice; NF-kappa B; Phosphorylation; Proto-Oncogene Proteins c-akt; Quercetin; Sepsis; Tumor Necrosis Factor-alpha |
顯示於: | 食品科技研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。