Anti-septic effects of pelargonidin on HMGB1-induced responses in vitro and in vivo

Abstract

A certain nucleosomal protein-high mobility group box-1 (HMGB1)-has recently been established as a late mediator of sepsis, with a relatively wide therapeutic window for pharmacological intervention. Pelargonidin (PEL) is a well-known red pigment found in plants; it has important biological activities that are potentially beneficial for human health. In the present study, we investigated whether PEL can modulate HMGB1-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. The anti-inflammatory activities of PEL were determined by measuring permeability, leukocyte adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs and mice, as well as the beneficial effects of PEL on survival rate in the mouse sepsis model. The data showed that PEL had effectively inhibited lipopolysaccharide (LPS)-induced release of HMGB1 and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. Furthermore, PEL inhibited the HMGB1-mediated production of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), as well as the activation of nuclear factor-kappa B (NF-kappa B) and extracellular signal-regulated kinases 1 and 2 (ERK1/2). Collectively, these results indicate that PEL could be used to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.