orientin and Sepsis

High mobility group box-1 (HMGB1) protein acts as a late mediator of severe vascular inflammatory conditions. Orientin has been known to have anxiolytic and antioxidative activities. However, the effect of orientin on HMGB1-induced inflammatory response has not been studied. We assessed this question by monitoring the effects of post-treatment orientin and its derivatives on lipopolysaccharide (LPS) and cecal 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. Post-treatment orientin was found to suppress LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangements. Orientin inhibited HMGB1-mediated hyperpermeability and leukocyte migration in septic mice. Orientin also induced down-regulation of CLP-induced release of HMGB1 and mortality. Collectively, these results suggest that orientin may be regarded as a candidate therapeutic agent for treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.

Topics: Animals; Cells, Cultured; Coinfection; Dose-Response Relationship, Drug; Flavonoids; Glucosides; HMGB1 Protein; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Male; Mice; Mice, Inbred C57BL; Sepsis