title: Esculin attenuates endotoxin shock induced by lipopolysaccharide in mouse and NO production in vitro through inhibition of NF-κB activation.
abstract: Esculin, a coumarin compound derived from the traditional Chinese herbs such as Cortex Fraxini, has long been used for treating inflammatory and vascular diseases. In present study, we analyzed the role of esculin against macrophages and endotoxin shock induced by lipopolysaccharide (LPS) in mice. Here, we demonstrated that esculin suppressed inflammatory reactions in macrophages and protected mice from LPS-induced endotoxin shock. We found that esculin significantly inhibited the production of nitric oxide (NO) production via the inhibition of nuclear factor-κB (NF-κB) activation in macrophages. In animal model, esculin pretreatment significantly improved the survival rate of mice. LPS-induced increase of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in serum, lung, liver and kidney were markedly inhibited by esculin. IL-10, an anti-inflammatory cytokine, was up-regulated by esculin. Moreover, the histopathological analyses showed that esculin significantly attenuated the tissues injury of lung, liver, kidney in endotoxic mice. In addition, esculin significantly diminished the protein expression of NF-κB p65 in lung, liver, kidney, which resulted in lower levels of inflammatory mediators. These results suggest that esculin may be a potential drug for treatment of various inflammatory diseases.
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, 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, Xi'an 710061, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Zehong
authors.initials: Z
authors.lastname: He
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Zhi
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: niuxf@mail.xjtu.edu.cn.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Niu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004929:Esculin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D009928:Organ Specificity; D012772:Shock, Septic / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004929:Esculin; D009569:Nitric Oxide
keywords: Endotoxin shock; Esculin; Macrophages; Nuclear factor-kappa B; Pro-inflammatory cytokines