Anti-septic effects of glyceollins in HMGB1-induced inflammatory responses in vitro and in vivo.

The ubiquitous nuclear protein High mobility group box 1 (HMGB1) is released by activated macrophages and human umbilical vein endothelial cells (HUVECs), and functions as a late mediator of experimental sepsis. Glyceollins (GCLs) are active compounds from Aspergillus sojae which have been reported for anti-cancer, anti-diabetes, and anti-inflammatory activities. We investigated here, the antiseptic effects and underlying mechanisms of GCLs against HMGB1-mediated septic responses in HUVECs and mice. According to the results, GCLs effectively inhibited lipopolysaccharide-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, GCLs suppressed the production of tumor necrosis factor-α and interleukin 6 and activation of nuclear factor-κB and extracellular regulated kinases 1/2 by HMGB1. Collectively, these results indicate that GCLs could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.