title: Isofraxidin protects mice from LPS challenge by inhibiting pro-inflammatory cytokines and alleviating histopathological changes.
abstract: Isofraxidin (IF), the major bioactive component of Sarcandra glabra, has been reported to be an effective anti-inflammatory compound. In a previous study, we showed that IF acts via the MAPK pathway to produce anti-inflammatory effects, both in vivo and in vitro. However, the effect and mechanism of action of IF on inflammatory cytokines and NF-κB activation in vivo has not been investigated. We therefore aimed to evaluate how IF regulates the production of inflammatory cytokines in vivo by intraperitoneal injection of IF (1, 5 or 15mg/kg) prior to treatment with LPS (1mg/kg, i.p.). Macroscopic, biochemical and histopathological parameters were measured. Treatment with IF prior to LPS challenge decreased mortality rate, body weight loss, organ coefficient and histopathological changes. IF also suppressed the protein expression of NF-κB, levels of NO and IL-6 in serum and production of TNF-α in liver. Our results show that pretreatment with IF increases the survival rate following LPS stimulation in mice. The effect involves regulation of NF-κB signal which, in turn, regulates production of inflammatory cytokine TNF-α, suggesting that IF may have a therapeutic effect against LPS-induced inflammatory disease.
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, No. 76, Western Yanta Road, Xi'an 710061, Shaanxi Province, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, No. 76, Western Yanta Road, Xi'an 710061, Shaanxi Province, PR China.
authors.forename: Qingli
authors.initials: Q
authors.lastname: Mu
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, No. 76, Western Yanta Road, Xi'an 710061, Shaanxi Province, PR China. Electronic address: liwf@mail.xjtu.edu.cn.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, No. 76, Western Yanta Road, Xi'an 710061, Shaanxi Province, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, No. 76, Western Yanta Road, Xi'an 710061, Shaanxi Province, PR China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, No. 76, Western Yanta Road, Xi'an 710061, Shaanxi Province, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, No. 76, Western Yanta Road, Xi'an 710061, Shaanxi Province, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, No. 76, Western Yanta Road, Xi'an 710061, Shaanxi Province, PR China. Electronic address: helc@mail.xjtu.edu.cn.
authors.forename: Langchong
authors.initials: L
authors.lastname: He
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D006321:Heart / Q000502:physiology; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism / Q000502:physiology; D008168:Lung / Q000502:physiology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D015996:Survival Rate; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D020011:Protective Agents; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C008182:isofraxidin; D009569:Nitric Oxide
keywords: Anti-inflammation; Histopathological changes; Isofraxidin; Nitric oxide; Nuclear factor-κB; Pro-inflammatory cytokines