title: Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model.
abstract: OBJECTIVE
  Asthma is an inflammatory disease that involves airway hyperresponsiveness and remodelling. Flavonoids have been associated to anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment of asthma. Our aim was to evaluate the effects of the sakuranetin treatment in several aspects of experimental asthma model in mice.
  
  
  METHODS
  Male BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin-sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO), sakuranetin (20 mg kg(-1) per mice) or dexamethasone (5 mg kg(-1) per mice) daily beginning from 24th to 29th day. Control group received saline inhalation and nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness, inflammation and remodelling as well as specific IgE antibody. RANTES, IL-5, IL-4, Eotaxin, IL-10, TNF-α, IFN-γ and GMC-SF content in lung homogenate was performed by Bioplex assay, and 8-isoprostane and NF-kB activations were visualized in inflammatory cells by immunohistochemistry.
  
  
  RESULTS
  We have demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness, inflammation and remodelling; and these effects could be attributed to Th2 pro-inflammatory cytokines and oxidative stress reduction as well as control of NF-kB activation.
  
  
  CONCLUSIONS
  These results highlighted the importance of counteracting oxidative stress by flavonoids in this asthma model and suggest sakuranetin as a potential candidate for studies of treatment of asthma.
authors.affiliation: Departments of Medicine, School of Medicine, University de São Paulo, São Paulo, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Toledo
authors.forename: C P P
authors.initials: CP
authors.lastname: Sakoda
authors.forename: A
authors.initials: A
authors.lastname: Perini
authors.forename: N M
authors.initials: NM
authors.lastname: Pinheiro
authors.forename: R M
authors.initials: RM
authors.lastname: Magalhães
authors.forename: S
authors.initials: S
authors.lastname: Grecco
authors.forename: I F L C
authors.initials: IF
authors.lastname: Tibério
authors.forename: N O
authors.initials: NO
authors.lastname: Câmara
authors.forename: M A
authors.initials: MA
authors.lastname: Martins
authors.forename: J H G
authors.initials: JH
authors.lastname: Lago
authors.forename: C M
authors.initials: CM
authors.lastname: Prado
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D000094162:Phytoalexins
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005419:Flavonoids; D016328:NF-kappa B; D010047:Ovalbumin; C099724:sakuranetin; D000094162:Phytoalexins