title: Naringenin has anti-inflammatory properties in macrophage and ex vivo human whole-blood models.
abstract: OBJECTIVE
  Periodontitis is a chronic inflammatory disease of bacterial etiology, affecting tooth-supporting tissues. The host inflammatory response to periodontopathogens, notably the high and continuous production of cytokines, is considered a major factor causing the local tissue destruction observed in periodontitis. The aim of the present study was to investigate the effect of naringenin, a major flavanone in grapefruits and tomatoes, on the lipopolysaccharide-induced pro-inflammatory cytokine production by host cells, using two different models.
  
  
  METHODS
  The effect of naringenin was characterized using macrophages stimulated with the lipopolysaccharide of either Aggregatibacter actinomycetemcomitans or Escherichia coli and using whole blood stimulated with A. actinomycetemcomitans lipopolysaccharide, in the presence or absence of naringenin. Lipopolysaccharide-induced interleukin-1 beta, interleukin-6, interleukin-8 and tumor necrosis factor-alpha production by macrophages and whole-blood samples treated with naringenin were evaluated using an enzyme-linked immunosorbent assay. Changes in the phosphorylation states of macrophage kinases induced by A. actinomycetemcomitans lipopolysaccharide and naringenin were characterized by immunoblot screening.
  
  
  RESULTS
  Our results clearly indicated that naringenin is a potent inhibitor of the pro-inflammatory cytokine response induced by lipopolysaccharide in both macrophages and in whole blood. Naringenin markedly inhibited the phosphorylation on serines 63 and 73 of Jun proto-oncogene-encoded AP-1 transcription factor in lipopolysaccharide-stimulated macrophages.
  
  
  CONCLUSIONS
  The results from the present study suggest that naringenin holds promise as a therapeutic agent for treating inflammatory diseases such as periodontitis.
authors.affiliation: Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, Quebec City, Quebec G1K 7P4, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Bodet
authors.forename: V D
authors.initials: VD
authors.lastname: La
authors.forename: F
authors.initials: F
authors.lastname: Epifano
authors.forename: D
authors.initials: D
authors.lastname: Grenier
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004926:Escherichia coli; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000187:drug effects; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D010518:Periodontitis / Q000097:blood*; D010766:Phosphorylation / Q000187:drug effects; D010770:Phosphotransferases / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors; D012694:Serine / Q000037:antagonists & inhibitors; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000187:drug effects; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D044950:Flavanones; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010770:Phosphotransferases; D017346:Protein Serine-Threonine Kinases; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D012694:Serine; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C000715470:MAS1 protein, human; C005273:naringenin