title: Escin Increases the Survival Rate of LPS-Induced Septic Mice Through Inhibition of HMGB1 Release from Macrophages.
abstract: BACKGROUND
  Previous studies have described the effects of Escin on improving the survival rate of endotoxemic animals. The purpose of this study was to explore the molecular mechanisms of this potentially beneficial treatment.
  
  
  METHODS
  First, the survival rate of endotoxemic mice was monitored for up to 2 weeks after Escin pretreatment, Escin post-treatment, or Escin post-treatment + rHMGB1. The effects of Escin on the release of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6 and HMGB1 in the serum of endotoxemic mice and LPS-induced macrophages were evaluated by ELISA. Furthermore, the mRNA and protein levels of HMGB1 in LPS-induced macrophages were measured by qRT-PCR and Western blot, respectively. Additionally, the release of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6 was evaluated by ELISA in rHMGB1-induced macrophages. Finally, the protein levels and the activity of NF-κB in macrophages were checked by Western blot and ELISA, respectively.
  
  
  RESULTS
  Both pretreatment and post-treatment with Escin could improve the survival rate of endotoxemic mice, while exogenous rHMGB1 reversed this effect. In addition, Escin decreased the level of the pro-inflammatory cytokinesTNF-α,IL-1β, IL-6 and HMGB1 in endotoxemic mice and in LPS-induced macrophages. Escin could also inhibit the mRNA levels and activity of HMGB1. The release of the pro-inflammatory cytokinesTNF-α,IL-1β, IL-6 could be suppressed in rHMGB1-induced macrophages by Escin. Finally, Escin could suppress the activation of NF- κB in LPS-induced macrophages.
  
  
  CONCLUSIONS
  Escin could improve the survival of mice with LPS-induced endotoxemia. This effect maybe meditated by reducing the release of HMGB1, resulting in the suppression of the release of pro-inflammatory cytokines.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Cheng
authors.forename: Hongrui
authors.initials: H
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Mao
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Deijun
authors.initials: D
authors.lastname: Yang
authors.forename: Ziran
authors.initials: Z
authors.lastname: Wei
authors.forename: Shunxiang
authors.initials: S
authors.lastname: Gao
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Lianghua
authors.initials: L
authors.lastname: Wang
authors.forename: Qingping
authors.initials: Q
authors.lastname: Cai
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000276:immunology; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D004928:Escin / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000097:blood / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D015996:Survival Rate
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D004928:Escin