title: Flavonols attenuate the immediate and late-phase asthmatic responses to aerosolized-ovalbumin exposure in the conscious guinea pig.
abstract: We previously reported that quercetin and rutin have potent, anti-asthmatic activity, but the structure-activity relationships of flavonoids and anti-asthmatic agents are still poorly understood. In the current study, the effects of kaempferol, fisetin, and morin on the immediate-phase response (IAR) and late-phase response (LAR) caused by exposure to aerosolized-ovalbumin (OA) in OA-sensitized guinea pigs were evaluated by determining the specific airway resistance (sRaw), recruitment of leukocytes and chemical mediators in bronchoalveolar lavage fluid (BALF), histopathological surveys, and determination of neutrophil chemotaxis. Fisetin and kaempherol (30 mg/kg, p.o.) significantly (P<0.01) inhibited sRaw by 47.93% and 30.05% in IAR, and 54.45% and 40.50% in LAR, when compared to vehicle control, respectively. Furthermore, all three studied flavonols (30 mg/kg, p.o.) significantly (P<0.05) inhibited the recruitment of total, as well as subtypes of, leukocytes into the lung BALF. This recruitment inhibition corresponded to the inhibition of leukocyte infiltration, particularly of eosinophils and neutrophils, into the lung in pathological surveys and formly-methionyl-leucyl-phenylalanine (FMLP)-induced neutrophil chemotaxis studies. Kaempferol inhibited FMLP-induced neutrophil chemotaxis in a concentration-dependent manner in a tested range of 1-100 μM. Fisetin inhibited histamine content and peroxidase (EPO) activity in BALF in a dose-dependent manner. All three tested flavonols significantly (P<0.01) inhibited histamine content at 10 mg/kg, and phospholipase A(2) (PLA(2)) and EPO activities at 30 mg/kg (p.o.) in BALF. Kaempherol had a greater anti-asthmatic effect than other flavonols. Fisetin demonstrated the greatest inhibition of sRaw, whereas morin had lesser effects. These results indicate that the lower the molecular weight, the greater the anti-asthmatic activities of these compounds.
authors.affiliation: Division of pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Chan Hun
authors.initials: CH
authors.lastname: Jung
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Lee
authors.forename: Jin Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Bong Jae
authors.initials: BJ
authors.lastname: Cho
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Sim
authors.forename: Chang Jong
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D018893:Bronchoalveolar Lavage; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D044948:Flavonols / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D044949:Kaempferols / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008970:Molecular Weight; D009240:N-Formylmethionine Leucyl-Phenylalanine; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D010047:Ovalbumin / Q000008:administration & dosage; D009195:Peroxidase / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D047309:Flavones
chemical_list: D000336:Aerosols; D018927:Anti-Asthmatic Agents; D005419:Flavonoids; D044948:Flavonols; D006632:Histamine; D044949:Kaempferols; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010047:Ovalbumin; D009195:Peroxidase; D054467:Phospholipases A2; D010936:Plant Extracts; C006552:kaempferol; C008548:morin; D047309:Flavones; C017875:fisetin