title: Andrographolide inhibits HMGB1-induced inflammatory responses in human umbilical vein endothelial cells and in murine polymicrobial sepsis.
abstract: OBJECTIVE
  Nuclear DNA-binding protein high-mobility group box 1 (HMGB1) protein acts as a late mediator of severe vascular inflammatory conditions, such as septic shock, upregulating pro-inflammatory cytokines. Andrographolide (AG) is isolated from the plant of Andrographis paniculata and used as a folk medicine for treatment of viral infection, diarrhoea, dysentery and fever. However, the effect of AG on HMGB1-induced inflammatory response has not been studied.
  
  
  METHODS
  Firstly, we accessed this question by monitoring the effects of post-treatment AG on lipopolysaccharide (LPS) and caecal ligation and puncture (CLP)-mediated release of HMGB1 and HMGB1-mediated regulation of pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and septic mice.
  
  
  RESULTS
  Post-treatment AG was found to suppress LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangements. AG also inhibited HMGB1-mediated hyperpermeability and leucocyte migration in septic mice. In addition, AG inhibited production of tumour necrosis factor-α (TNF-α) and activation of AKT, nuclear factor-κB (NF-κB) and extracellular-regulated kinases (ERK) 1/2 by HMGB1 in HUVECs. AG also induced downregulation of CLP-induced release of HMGB1, production of interleukin (IL) 1β/6/8 and mortality.
  
  
  CONCLUSIONS
  Collectively, these results suggest that AG may be regarded as a candidate therapeutic agent for the treatment of vascular inflammatory diseases via inhibition of the HMGB1 signalling pathway.
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: W
authors.initials: W
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Ku
authors.forename: H
authors.initials: H
authors.lastname: Yoo
authors.forename: K
authors.initials: K
authors.lastname: Song
authors.forename: J
authors.initials: J
authors.lastname: Bae
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D024243:HMGB1 Protein; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004224:Diterpenes; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; C030419:andrographolide
keywords: Andrographolide; HMGB1; sepsis; vascular inflammation