ovalbumin and astragalin

Topics: Animals; Chemokine CCL2; Disease Models, Animal; Humans; Intercellular Adhesion Molecule-1; Kaempferols; Lung Diseases, Obstructive; Macrophages; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin

Fibrotic remodeling of airway and lung parenchymal compartments is attributed to pulmonary dysfunction with an involvement of reactive oxygen species (ROS) in chronic lung diseases such as idiopathic pulmonary fibrosis and asthma.. The in vitro study elucidated inhibitory effects of astragalin, kaempferol-3-O-glucoside from leaves of persimmon and green tea seeds, on oxidative stress-induced airway fibrosis. The in vivo study explored the demoting effects of astragalin on epithelial to mesenchymal transition in BALB/c mice sensitized with ovalbumin (OVA).. The exposure of 20 μM H2O2 for 72 h accelerated E-cadherin loss and vimentin induction in airway epithelial BEAS-2B cells, which was reversed by non-toxic astragalin at 1-20 μM. Astragalin allayed the airway tissue levels of ROS and vimentin enhanced by OVA challenge. Collagen type 1 production increased in H2O2-exposed epithelial cells and collagen fiber deposition was observed in OVA-challenged mouse airways. This study further investigated that the oxidative stress-triggered autophagic regulation was responsible for inducing airway fibrosis. H2O2 highly enhanced the expression induction of the autophagy-related beclin-1 and light chains 3A/B (LC3A/B) within 4 h and astragalin blocked such induction by H2O2. This compound deterred the ROS-promoted autophagosome formation in BEAS-2B cells. Consistently, in OVA-sensitized mice the expression of beclin-1 and LC3A/B was highly induced, and oral administration of astragalin suppressed the autophagosome formation with inhibiting the induction of these proteins in OVA-challenged airway subepithelium. Induction of autophagy by spermidine influenced the epithelial induction of E-cadherin and vimentin that was blocked by treating astragalin.. These results demonstrate that astragalin can be effective in allaying ROS-promoted bronchial fibrosis through inhibiting autophagosome formation in airways.

Topics: Airway Remodeling; Animals; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Cdh1 Proteins; Cell Line; Collagen Type I; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Epithelial Cells; Epithelial-Mesenchymal Transition; Humans; Hydrogen Peroxide; Kaempferols; Lung; Male; Membrane Proteins; Mice, Inbred BALB C; Microtubule-Associated Proteins; Ovalbumin; Pulmonary Fibrosis; Reactive Oxygen Species; Signal Transduction; Spermidine; Time Factors; Vimentin

The present study aimed to determine the protective effects and the underlying mechanisms of astragalin (AG) on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Our study demonstrated that AG inhibited OVA-induced increases in eosinophil count; IL-4, IL-5, IL-13, and IgE were recovered in bronchoalveolar lavage fluid, and increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that AG substantially inhibited OVA-induced eosinophilia in lung tissue. Western blot analysis demonstrated that AG treatments markedly inhibited OVA-induced SOCS-3 expression and enhancement of SOCS-5 expression in an asthma model. Our findings support the possible use of AG as a therapeutic drug for patients with allergic asthma.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Female; Inflammation; Inflammation Mediators; Kaempferols; Mice; Mice, Inbred BALB C; Ovalbumin