Abstract
BackgroundFibrotic 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.MethodsThe 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).ResultsThe 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.ConclusionThese results demonstrate that astragalin can be effective in allaying ROS-promoted bronchial fibrosis through inhibiting autophagosome formation in airways.
Highlights
Autophagy, a catabolic process, plays a role in the elimination of damaged organelles and protein aggregates and in the turnover of essential proteins [1,2]
Oxidative stress may instigate epithelial to mesenchymal transition (EMT) process and fibrosis in airways, which can be disturbed by supplementing astragalin to the epithelium
This study investigated the potential of astragalin as a modulator antagonizing oxidative stress-associated autophagy leading to pulmonary fibrosis
Summary
A catabolic process, plays a role in the elimination of damaged organelles and protein aggregates and in the turnover of essential proteins [1,2]. This process is activated by a diverse array of cellular stressors such as endoplasmic reticulum (ER) stress and microbial infection [3,4]. There is an emerging body of evidence that autophagy regulates various cellular processes and cell fates, including cellular death and senescence, inflammation and immune. Some environmental factors such as air pollutants may cause an extreme increase of reactive oxygen species (ROS) generation in the airways [8]. 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
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