title: Attenuation of airway hyperreactivity and T helper cell type 2 responses by coumarins from Peucedanum praeruptorum Dunn in a murine model of allergic airway inflammation.
abstract: BACKGROUND
  The root of Peucedanum praeruptorum Dunn (PPD) is a commonly used traditional Chinese medicine for the treatment of asthma. Its major constituents, coumarins, were presumed to be responsible for its efficacy.
  
  
  OBJECTIVE
  The potential of coumarins from PPD (CPPD) as anti-asthma agent was investigated.
  
  
  METHODS
  Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic airway inflammation. CPPD was administered intragastrically before every OVA challenge. Airway reactivity to the intravenous administration of acetylcholine chloride was measured 48h after final OVA inhalation. Airway inflammation was evaluated by leukocyte counts of bronchoalveolar lavage fluid (BALF) and histopathological analysis of lung lesions. Levels of interleukin (IL)-4, IL-5, IL-10, IL-13 and IFN-γ in BALF and OVA-specific immunoglobulin (Ig) E in serum, and activity of eosinophil peroxidase (EPO) in lung was measured. The percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells among CD4(+) T cells in spleen was analyzed by flow cytometry.
  
  
  RESULTS
  Compared with model group, CPPD significantly reduced airway hyperreactivity and airway eosinophilic inflammation, improved pathologic lesion of the lungs, reduced levels of IL-4, IL-5, IL-13 in BALF and OVA-specific IgE in serum, inhibited the activities of EPO in lung, and up-regulated levels of IL-10 and IFN-γ in BALF as well as the percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells in spleen.
  
  
  CONCLUSIONS
  CPPD can significantly suppress OVA-induced airway inflammation, airway hyperreactivity and Th2 predominant response in mice, showing great therapeutic potential for the treatment of allergic asthma.
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China.
authors.forename: You-Yi
authors.initials: YY
authors.lastname: Xiong
authors.forename: Fei-Hua
authors.initials: FH
authors.lastname: Wu
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D000109:Acetylcholine; D000818:Animals; D018926:Anti-Allergic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000941:Antigens; D019661:Apiaceae / Q000737:chemistry; D001249:Asthma / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016085:Bronchoconstrictor Agents; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D008517:Phytotherapy; D018517:Plant Roots; D010946:Plants, Medicinal; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000517:prevention & control; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D000941:Antigens; D016085:Bronchoconstrictor Agents; D003374:Coumarins; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D010047:Ovalbumin; D000109:Acetylcholine