Vascular barrier protective effects of piperlonguminine in vitro and in vivo.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results indicate that PL could be a candidate therapeutic agent for various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea.
Sae-Kwang
SK
Ku
Jeong Ah
JA
Kim
Jong-Sup
JS
Bae
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004148:Dioxolanes / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D024243:HMGB1 Protein / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D010881:Piperidones
D004148:Dioxolanes; D048049:Extracellular Signal-Regulated MAP Kinases; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; D048051:p38 Mitogen-Activated Protein Kinases; C582808:HMGB1 protein, mouse; C498077:piperlongumine; D010881:Piperidones