title: Preventive and curative glycoside kaempferol treatments attenuate the TH2-driven allergic airway disease.
abstract: Asthma is a chronic respiratory disease characterized by airway inflammation and airway hyperresponsiveness (AHR). One strategy to treat allergic diseases is the development of new drugs. Flavonoids are compounds derived from plants and are known to have antiallergic, anti-inflammatory, and antioxidant properties. To investigate whether the flavonoid kaempferol glycoside 3-O-[beta-d-glycopiranosil-(1-->6)-alpha-l-ramnopiranosil]-7-O-alpha-l-ramnopiranosil-kaempferol (GRRK) would be capable of modulating allergic airway disease (AAD) either as a preventive (GRRK P) or curative (GRRK C) treatment in an experimental model of asthma. At weekly intervals, BALB/c mice were subcutaneously (sc) sensitized twice with ovalbumin (OVA)/alum and challenged twice with OVA administered intranasally. To evaluate any preventive effect, GRRK was administered 1h (hour) before each OVA-sensitization and challenge, while to analyze the curative effect, mice were first sensitized with OVA, followed by GRRK given at day 18 through 21. The onset of AAD was evaluated 24h after the last OVA challenge. Both treatments resulted in a dose-dependent reduction in total leukocyte and eosinophil counts in the bronchoalveolar lavage fluid (BAL). GRRK also decreased CD4(+), B220(+), MHC class II and CD40 molecule expressions in BAL cells. Histology and lung mechanic showed that GRRK suppressed mucus production and ameliorated the AHR induced by OVA challenge. Furthermore, GRRK impaired Th2 cytokine production (IL-5 and IL-13) and did not induce a Th1 pattern of inflammation. These findings demonstrate that GRRK treatment before or after established allergic lung disease down-regulates key asthmatic features. Therefore, GRRK has a potential clinical use for the treatment of allergic asthma.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Brazil.
authors.forename: K C P
authors.initials: KC
authors.lastname: Medeiros
authors.forename: L
authors.initials: L
authors.lastname: Faustino
authors.forename: E
authors.initials: E
authors.lastname: Borduchi
authors.forename: R J B
authors.initials: RJ
authors.lastname: Nascimento
authors.forename: T M S
authors.initials: TM
authors.lastname: Silva
authors.forename: E
authors.initials: E
authors.lastname: Gomes
authors.forename: M R
authors.initials: MR
authors.lastname: Piuvezam
authors.forename: M
authors.initials: M
authors.lastname: Russo
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D001249:Asthma / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004187:Disaccharides / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification; D004804:Eosinophils / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006027:Glycosides / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D044949:Kaempferols / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification; D007962:Leukocytes / Q000187:drug effects* / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D015703:Antigens, CD; D004187:Disaccharides; D006027:Glycosides; D000949:Histocompatibility Antigens Class II; D018793:Interleukin-13; D015848:Interleukin-5; D044949:Kaempferols; D010047:Ovalbumin