Ameliorative effect of a rarely occurring C-methylrotenoid on HMGB1-induced septic responses in vitro and in vivo.
The ubiquitous nuclear protein, high mobility group box-1 (HMGB1) functions as a late mediator of sepsis. A new rarely occurring C-methylrotenoid, named boeravinone X (comp 1), was isolated and identified from Abronia nana suspension cultures during our continuous works on the discovery of anti-septic natural products. Here, we investigated the antiseptic effects and underlying mechanisms of comp 1 against HMGB1-mediated septic responses. According to the results, comp 1 effectively inhibited lipopolysaccharide (LPS)-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. And, comp 1 suppressed the production of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), and the activation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) by HMGB1. Collectively, these results indicate that comp 1 could be potential therapeutic agents for the treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea.
Eun-Ju
EJ
Yang
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea.
Wonhwa
W
Lee
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address: kssong@knu.ac.kr.
Kyung-Sik
KS
Song
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address: baejs@knu.ac.kr.
Jong-Sup
JS
Bae
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D039281:Nyctaginaceae / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D005419:Flavonoids; D024243:HMGB1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C582808:HMGB1 protein, mouse; C000617995:boeravinone X; C577686:interleukin-6, mouse; C535148:Mapk1 protein, mouse
Abronia nana; C-Methylrotenoid; HMGB1; HUVEC; Inflammation; Sepsis