title: Astragaloside IV protects against polymicrobial sepsis through inhibiting inflammatory response and apoptosis of lymphocytes.
abstract: BACKGROUND
  Sepsis is a major clinical challenge in modern medicine, representing one of the leading causes of death in developed countries. The syndrome is a consequence of a dysregulated immune response, including early uncontrolled systemic inflammation and prolonged immunosuppression in the late phase. The present study was conducted to investigate the therapeutic effects of astragaloside IV (ASI-IV) on the cecal ligation and puncture (CLP)-induced sepsis in mice.
  
  
  METHODS
  C57BL/6 mice were randomly divided into sham control + vehicle, CLP + vehicle, and CLP + ASI-IV groups. ASI-IV (3 mg/kg) was intravenously injected 1 h after CLP surgery. Survival rate, bacterial clearance, inflammatory mediators, phagocytes emigration, histopathology, and lymphocyte apoptosis were examined. The effects of ASI-IV on peritoneal macrophage activation and its underlying mechanisms were also evaluated.
  
  
  RESULTS
  We reported that treatment with ASI-IV significantly improved survival in septic mice. In agreement with this protective effect, the pathologic damage that was typically seen in lung and spleen was ameliorated; the level of bacterial burden was lessened; inflammatory cytokines and chemokines in circulation were profoundly reduced; lymphocyte apoptosis was inhibited. ASI-IV suppressed LPS-induced macrophage activation through inhibiting NF-κB and ERK1/2 signaling pathways.
  
  
  CONCLUSIONS
  ASI-IV protected mice against polymicrobial sepsis by inhibiting inflammatory response and lymphocyte apoptosis. Therefore, ASI-IV might provide a novel therapeutic approach for septic patients.
authors.affiliation: Department of Anesthesiology, Fuzhou General Hospital of Nanjing Military Command, Fujian Medical University, Fuzhou, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Fuzhou General Hospital of Nanjing Military Command, Fujian Medical University, Fuzhou, China.
authors.forename: Hequn
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Navy General Hospital, Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Anesthesiology, No.521 Hospital of PLA, Baicheng, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Fuzhou General Hospital of Nanjing Military Command, Fujian Medical University, Fuzhou, China. Electronic address: wuxiaozhi7410@126.com.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D016207:Cytokines / Q000097:blood; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008214:Lymphocytes / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010586:Phagocytes / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D020011:Protective Agents; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A
keywords: Apoptosis; Astragaloside; Immunosuppression; Inflammation; Sepsis