title: Cranberry proanthocyanidins act in synergy with licochalcone A to reduce Porphyromonas gingivalis growth and virulence properties, and to suppress cytokine secretion by macrophages.
abstract: OBJECTIVE
  Periodontitis is an inflammatory disease of polymicrobial origin that affects the tooth-supporting tissues. With the spread of antibiotic resistance among pathogenic bacteria, alternative strategies are required to better control infectious diseases such as periodontitis. The aim of our study was to investigate whether two natural compounds, A-type cranberry proanthocyanidins (AC-PACs) and licochalcone A, act in synergy against Porphyromonas gingivalis and the host inflammatory response of a macrophage model.
  
  
  RESULTS
  Using a checkerboard microtitre test, AC-PACs and licochalcone A were found to act in synergy to inhibit P. gingivalis growth and biofilm formation. Fluorescein isothiocyanate-labelled P. gingivalis adhesion to oral epithelial cells was also inhibited by a combination of the two natural compounds in a synergistic manner. Fluorometric assays showed that although AC-PACs and licochalcone A reduced both MMP-9 and P. gingivalis collagenase activities, no synergy was obtained with a combination of the compounds. Lastly, AC-PACs and licochalcone A also acted in synergy to reduce the lipopolysaccharide (LPS)-induced secretion of the pro-inflammatory mediators IL-1β, TNF-α, IL-6 and IL-8 in a macrophage model.
  
  
  CONCLUSIONS
  A-type cranberry proanthocyanidins and licochalcone A, natural compounds from cranberry and licorice, respectively, act in synergy on both P. gingivalis and the host immune response, the two principal etiological factors of periodontitis.
  
  
  CONCLUSIONS
  The combined use of AC-PACs and licochalcone A may be a potential novel therapeutic strategy for the treatment and prevention of periodontal disease.
authors.affiliation: Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Quebec City, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Feldman
authors.forename: D
authors.initials: D
authors.lastname: Grenier
mesh_terms: D018441:Biofilms / Q000187:drug effects; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D003012:Microbial Collagenase / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D044945:Proanthocyanidins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D029799:Vaccinium macrocarpon / Q000737:chemistry*; D014774:Virulence
chemical_list: D047188:Chalcones; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010936:Plant Extracts; D044945:Proanthocyanidins; D014409:Tumor Necrosis Factor-alpha; D003012:Microbial Collagenase; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C070840:licochalcone A