title: Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling.
abstract: Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA-) sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs) were challenged by tumor necrosis factor alpha (TNF-α). The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK) evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL-) 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2',7'-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were abolished by morin, implying that ROS/MAPK signaling contributes to the relief of airway inflammation. Our findings indicate for the first time that morin alleviates airway inflammation in chronic asthma, which probably occurs via the oxidative stress-responsive MAPK pathway, highlighting a novel profile of morin as a potent agent for asthma management.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Ge
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, 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, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
authors.forename: Ning-Fei
authors.initials: NF
authors.lastname: Ji
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, 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, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
authors.forename: Jia-Xiang
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, 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, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
authors.forename: Mao
authors.identifier: 0000-0001-6901-8434
authors.initials: M
authors.lastname: Huang
mesh_terms: D000818:Animals; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D018384:Oxidative Stress / Q000187:drug effects*; D011014:Pneumonia / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D047309:Flavones
chemical_list: D003094:Collagen; D016207:Cytokines; D005419:Flavonoids; D007073:Immunoglobulin E; D008315:Malondialdehyde; D020780:Matrix Metalloproteinase 9; D010047:Ovalbumin; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C008548:morin; D047309:Flavones