Background: Fibrotic remodeling of airway and lung parenchymal compartments is attributed to pulmonary\ndysfunction with an involvement of reactive oxygen species (ROS) in chronic lung diseases such as idiopathic\npulmonary fibrosis and asthma.\nMethods: The in vitro study elucidated inhibitory effects of astragalin, kaempferol-3-O-glucoside from leaves of\npersimmon and green tea seeds, on oxidative stress-induced airway fibrosis. The in vivo study explored the demoting\neffects of astragalin on epithelial to mesenchymal transition in BALB/c mice sensitized with ovalbumin (OVA).\nResults: The exposure of 20 ?M H2O2 for 72 h accelerated E-cadherin loss and vimentin induction in airway epithelial\nBEAS-2B cells, which was reversed by non-toxic astragalin at 1ââ?¬â??20 ?M. Astragalin allayed the airway tissue levels of ROS\nand vimentin enhanced by OVA challenge. Collagen type 1 production increased in H2O2ââ?¬â??exposed epithelial cells and\ncollagen fiber deposition was observed in OVA-challenged mouse airways. This study further investigated that\nthe oxidative stress-triggered autophagic regulation was responsible for inducing airway fibrosis. H2O2 highly\nenhanced the expression induction of the autophagy-related beclin-1 and light chains 3A/B (LC3A/B) within 4 h\nand astragalin blocked such induction by H2O2. This compound deterred the ROS-promoted autophagosome\nformation in BEAS-2B cells. Consistently, in OVA-sensitized mice the expression of beclin-1 and LC3A/B was\nhighly induced, and oral administration of astragalin suppressed the autophagosome formation with inhibiting\nthe induction of these proteins in OVA-challenged airway subepithelium. Induction of autophagy by spermidine\ninfluenced the epithelial induction of E-cadherin and vimentin that was blocked by treating astragalin.\nConclusion: These results demonstrate that astragalin can be effective in allaying ROS-promoted bronchial\nfibrosis through inhibiting autophagosome formation in airways.
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