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 language | English |
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Pages (from-to) | 176-187 |
Number of pages | 12 |
Journal | Acta Physiologica |
Volume | 211 |
Issue number | 1 |
DOIs | |
State | Published - May 2014 |
Keywords
- Andrographolide
- HMGB1
- Sepsis
- Vascular inflammation