title: Protective Effects of Nobiletin Against Endotoxic Shock in Mice Through Inhibiting TNF-α, IL-6, and HMGB1 and Regulating NF-κB Pathway.
abstract: Nobiletin (NOB), the major bioactive component of polymethoxyflavones in citrus fruits, has been reported possessing significant biological properties. The purpose of the present study was to investigate the protective role of NOB on lipopolysaccharide (LPS)-induced endotoxic shock in mice. We found pretreatment with NOB increases the survival rate of mice after endotoxin injection. The present study clearly demonstrates that pretreatment with NOB decreases the production of early pro-inflammatory cytokines TNF-α, IL-6, and late-phase mediator HMGB1 in serum and tissues of kidney, lung, and liver. The histopathological study indicates that NOB administration significantly attenuate tissues injury induced by LPS. Moreover, NOB suppresses the activity of nuclear factor-kappa B (NF-κB). These results suggest that NOB protects mice against LPS-induced endotoxic shock through inhibiting the production of TNF-α, IL-6, and HMGB1 and the activation of NF-κB, which elucidate that NOB may be a promising drug candidate for the treatment of septic shock.
authors: School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, Shaanxi Province, 710061, People's Republic of China.
authors: Weifeng
authors: W
authors: Li
authors: School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, Shaanxi Province, 710061, People's Republic of China.
authors: Xiumei
authors: X
authors: Wang
authors: School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, Shaanxi Province, 710061, People's Republic of China. niuxf@mail.xjtu.edu.cn.
authors: Xiaofeng
authors: X
authors: Niu
authors: School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, Shaanxi Province, 710061, People's Republic of China.
authors: Hailin
authors: H
authors: Zhang
authors: School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, Shaanxi Province, 710061, People's Republic of China.
authors: Zehong
authors: Z
authors: He
authors: School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, Shaanxi Province, 710061, People's Republic of China.
authors: Yu
authors: Y
authors: Wang
authors: School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, Shaanxi Province, 710061, People's Republic of China.
authors: Wenbing
authors: W
authors: Zhi
authors: School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, Shaanxi Province, 710061, People's Republic of China.
authors: Fang
authors: F
authors: Liu
mesh_terms: D000818:Animals; D047309:Flavones / Q000009:adverse effects / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D012772:Shock, Septic / Q000188:drug therapy / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood; D000093242:Interleukin-6 Inhibitors
chemical_list: D047309:Flavones; D024243:HMGB1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C582808:HMGB1 protein, mouse; C008661:nobiletin
keywords: NF-κB; endotoxic shock; nobiletin; pro-inflammatory cytokine