title: Inhibition of airway inflammation, hyperresponsiveness and remodeling by soy isoflavone in a murine model of allergic asthma.
abstract: Epidemiologic studies have associated higher dietary consumption of soy isoflavones with decreased self-report of cough and allergic respiratory symptoms, but the pharmacodynamic effects of soy isoflavone on asthmatic model have not been well-described. Here, we hypothesized that soy isoflavone may have potential effects on airway hyperresponsiveness, inflammation and airway remodeling in a murine of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts, and for cytokine levels. Lung tissues were examined for cell infiltration, mucus hypersecretion and airway remodeling, and for the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Oral administration of soy isoflavone significantly reduced ovalbumin-induced airway hyperresponsiveness to intravenous methacholine, and inhibited ovalbumin-induced increases in eosinophil counts. RT-PCR analysis of whole lung lysates revealed that soy isoflavone markedly suppressed ovalbumin-induced mRNA expression of eotaxin, interleukin(IL)-5, IL-4 and matrix metalloproteinase-9, and increased mRNA expression of interferon (IFN)-γ and tissue inhibitor of metalloproteinase-1 in a dose-dependent manner. Soy isoflavone also substantially recovered IFN-γ/IL-4 (Th1/Th2) levels in bronchoalveolar lavage fluid. In addition, histologic studies showed that soy isoflavone dramatically inhibited ovalbumin-induced lung tissue eosinophil infiltration, airway mucus production and collagen deposition in lung tissues. Our findings suggest that soy isoflavone as nutritional supplement may provide a novel means for the treatment of airway inflammatory disease.
authors.affiliation: Taizhou University School of Medicine, Jiaojiang 371000, China.
authors.forename: Zhao-Seng
authors.initials: ZS
authors.lastname: Bao
authors.forename: Ling
authors.initials: L
authors.lastname: Hong
authors.forename: Yan
authors.initials: Y
authors.lastname: Guan
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: Dong
authors.forename: Hua-Sheng
authors.initials: HS
authors.lastname: Zheng
authors.forename: Gong-Li
authors.initials: GL
authors.lastname: Tan
authors.forename: Qiang-Min
authors.initials: QM
authors.lastname: Xie
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D054413:Chemokine CCL11 / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D010047:Ovalbumin / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013025:Glycine max / Q000737:chemistry; D013482:Superoxide Dismutase / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D015848:Interleukin-5; D007529:Isoflavones; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D016210:Methacholine Chloride; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D003094:Collagen; D009195:Peroxidase; D013482:Superoxide Dismutase; D020780:Matrix Metalloproteinase 9