Orientin inhibits HMGB1-induced inflammatory responses in HUVECs and in murine polymicrobial 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.
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Republic of Korea.
Hayoung
H
Yoo
Sae-Kwang
SK
Ku
Taeho
T
Lee
Jong-Sup
JS
Bae
D000818:Animals; D002478:Cells, Cultured; D060085:Coinfection / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism
D005419:Flavonoids; D005960:Glucosides; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C065886:orientin