Andrographolide inhibits HMGB1-induced inflammatory responses in human umbilical vein endothelial cells and in murine polymicrobial sepsis

W. Lee, S. Ku, H. Yoo, K. Song, J. Bae

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Aim: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)176-187
Number of pages12
JournalActa Physiologica
Volume211
Issue number1
DOIs
StatePublished - May 2014

Keywords

  • Andrographolide
  • HMGB1
  • Sepsis
  • Vascular inflammation

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