We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Andrographolide inhibits HMGB1-induced inflammatory responses in human umbilical vein endothelial cells and in murine polymicrobial sepsis.
- Authors
Lee, W.; Ku, S.; Yoo, H.; Song, K.; Bae, J.
- 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) 1 β/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.
- Subjects
INFLAMMATION; UMBILICAL veins; ENDOTHELIAL cells; SEPTICEMIA prevention; LABDANES; DITERPENES
- Publication
Acta Physiologica, 2014, Vol 211, Issue 1, p176
- ISSN
1748-1708
- Publication type
Article
- DOI
10.1111/apha.12264