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Andrographolide inhibits HMGB 1‐induced inflammatory responses in human umbilical vein endothelial cells and in murine polymicrobial sepsis
Author(s) -
Lee W.,
Ku S.,
Yoo H.,
Song K.,
Bae J.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12264
Subject(s) - andrographolide , umbilical vein , medicine , lipopolysaccharide , tumor necrosis factor alpha , immunology , sepsis , mapk/erk pathway , nf κb , proinflammatory cytokine , pharmacology , inflammation , tlr4 , kinase , biology , microbiology and biotechnology , biochemistry , in vitro
Aim Nuclear DNA ‐binding protein high‐mobility group box 1 ( HMGB 1) 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 HMGB 1‐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 HMGB 1 and HMGB 1‐mediated regulation of pro‐inflammatory responses in human umbilical vein endothelial cells ( HUVEC s) and septic mice. Results Post‐treatment AG was found to suppress LPS ‐mediated release of HMGB 1 and HMGB 1‐mediated cytoskeletal rearrangements. AG also inhibited HMGB 1‐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‐ κ B ( NF ‐ κ B) and extracellular‐regulated kinases ( ERK ) 1/2 by HMGB 1 in HUVEC s. AG also induced downregulation of CLP ‐induced release of HMGB 1, 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 HMGB 1 signalling pathway.