Vascular barrier protective effects of piperlonguminine in vitro and in vivo

Abstract

The nuclear DNA binding protein known as high-mobility group box 1 (HMGB1) acts as a late mediator of severe vascular inflammatory conditions, such as sepsis and septic shock. Piperlonguminine (PL), an important component of Piper longum fruit, is known to exhibit anti-hyperlipidemic, anti-platelet, and anti-melanogenesis activities. However, little is known about its effects on HMGB1-mediated inflammatory response. We investigated the effects of PL on HMGB1-mediated inflammatory response by monitoring the effects of PL on lipopolysaccharide or cecal ligation and puncture (CLP)-mediated release of HMGB1, as well as on the modulation of HMGB1-mediated inflammatory responses. According to our data, PL caused inhibition of the release of HMGB1 and downregulation of HMGB1-dependent inflammatory responses in human endothelial cells. PL also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with PL reduced the CLP-induced release of HMGB1 and sepsis-related mortality. These results indicate that PL could be a candidate therapeutic agent for various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.