pellitorine and Sepsis

High mobility group box 1 (HMGB1) acts as a late mediator of vascular inflammatory conditions. Pellitorine (PT), an active amide compound from Asarum sieboldii, is known to possess antibacterial and anticancer properties. In this study, we investigated the anti-septic effects of PT against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) induced by HMGB1 and the associated signaling pathways. According to our findings, treatment with PT resulted in inhibited release of HMGB1, down-regulation of HMGB1-dependent inflammatory responses in HUVECs, and inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with PT resulted in reduced cecal ligation and puncture (CLP)-induced release of HMGB1 and sepsis-related mortality. PT suppressed the production of tumor necrosis factor-α and interleukin 6 and the activation of nuclear factor-κB and extracellular regulated kinases 1/2 by HMGB1. Collectively, these results indicate the potential of PT as a candidate therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.

Topics: Animals; Anti-Infective Agents, Local; Anti-Inflammatory Agents; Capillary Permeability; Cell Adhesion; Cell Movement; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Fatty Acids, Unsaturated; HMGB1 Protein; Human Umbilical Vein Endothelial Cells; Humans; Inflammation Mediators; Interleukin-6; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-kappa B; Polyunsaturated Alkamides; Sepsis; Signal Transduction; Time Factors; Tumor Necrosis Factor-alpha