title: In vitro effects of anthocyanidins on sinonasal epithelial nitric oxide production and bacterial physiology.
abstract: BACKGROUND
  T2R bitter taste receptors play a crucial role in sinonasal innate immunity by upregulating mucociliary clearance and nitric oxide (NO) production in response to bitter gram-negative quorum-sensing molecules in the airway surface liquid. Previous studies showed that phytochemical flavonoid metabolites, known as anthocyanidins, taste bitter and have antibacterial effects. Our objectives were to examine the effects of anthocyanidins on NO production by human sinonasal epithelial cells and ciliary beat frequency, and their impact on common sinonasal pathogens Pseudomonas aeruginosa and Staphylococcus aureus.
  
  
  METHODS
  Ciliary beat frequency and NO production were measured by using digital imaging of differentiated air-liquid interface cultures prepared from primary human cells isolated from residual surgical material. Plate-based assays were used to determine the effects of anthocyanidins on bacterial swimming and swarming motility. Biofilm formation and planktonic growth were also assessed.
  
  
  RESULTS
  Anthocyanidin compounds triggered epithelial cells to produce NO but not through T2R receptors. However, anthocyanidins did not impact ciliary beat frequency. Furthermore, they did not reduce biofilm formation or planktonic growth of P. aeruginosa. In S. aureus, they did not reduce planktonic growth, and only one compound had minimal antibiofilm effects. The anthocyanidin delphinidin and anthocyanin keracyanin were found to promote bacterial swimming, whereas anthocyanidin cyanidin and flavonoid myricetin did not. No compounds that were tested inhibited bacterial swarming.
  
  
  CONCLUSIONS
  Results of this study indicated that, although anthocyanidins may elicited an innate immune NO response from human cells, they do not cause an increase in ciliary beating and they may also cause a pathogenicity-enhancing effect in P. aeruginosa. Additional studies are necessary to understand how this would affect the use of anthocyanidins as therapeutics. This study emphasized the usefulness of in vitro screening of candidate compounds against multiple parameters of both epithelial and bacterial physiologies to prioritize candidates for in vivo therapeutic testing.
authors.affiliation: department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Hariri
authors.forename: Sakeena J
authors.initials: SJ
authors.lastname: Payne
authors.forename: Bei
authors.initials: B
authors.lastname: Chen
authors.forename: Corrine
authors.initials: C
authors.lastname: Mansfield
authors.forename: Laurel J
authors.initials: LJ
authors.lastname: Doghramji
authors.forename: Nithin D
authors.initials: ND
authors.lastname: Adappa
authors.forename: James N
authors.initials: JN
authors.lastname: Palmer
authors.forename: David W
authors.initials: DW
authors.lastname: Kennedy
authors.forename: Masha Y
authors.initials: MY
authors.lastname: Niv
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D018441:Biofilms / Q000187:drug effects; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology; D000098706:Taste Receptors, Type 2
chemical_list: D000872:Anthocyanins; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D009569:Nitric Oxide