title: Galangin attenuates airway remodelling by inhibiting TGF-β1-mediated ROS generation and MAPK/Akt phosphorylation in asthma.
abstract: Galangin, a natural flavonol, has attracted much attention for its potential anti-inflammatory properties. However, its role in the regulation of airway remodelling in asthma has not been explored. The present study aimed to elucidate the effects of galangin on chronic inflammation and airway remodelling and to investigate the underlying mechanisms both in vivo and in vitro. Ovalbumin (OVA)-sensitised mice were administered with galangin 30 min before challenge. Our results showed that severe inflammatory responses and airway remodelling occurred in OVA-induced mice. Treatment with galangin markedly attenuated the leakage of inflammatory cells into bronchoalveolar lavage fluid (BALF) and decreased the level of OVA-specific IgE in serum. Galangin significantly inhibited goblet cell hyperplasia, collagen deposition and α-SMA expression. Lowered level of TGF-β1 and suppressed expression of VEGF and MMP-9 were observed in BALF or lung tissue, implying that galangin has an optimal anti-remodelling effect in vivo. Consistently, the TGF-β1-induced proliferation of airway smooth muscle cells was reduced by galangin in vitro, which might be due to the alleviation of ROS levels and inhibition of MAPK pathway. Taken together, the present findings highlight a novel role for galangin as a promising anti-remodelling agent in asthma, which likely involves the TGF-β1-ROS-MAPK pathway.
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Wang-Jian
authors.initials: WJ
authors.lastname: Zha
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Ge
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Zeng
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Huang
mesh_terms: D000199:Actins / Q000378:metabolism; D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D005419:Flavonoids / Q000494:pharmacology*; D020397:Goblet Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010047:Ovalbumin / Q000009:adverse effects; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000199:Actins; D005419:Flavonoids; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C544013:alpha-smooth muscle actin, mouse; C037032:galangin; D007073:Immunoglobulin E; D010047:Ovalbumin; D003094:Collagen; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9