Astragalin inhibits autophagy-associated airway epithelial fibrosis.

Abstract

BACKGROUND:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSION:

These results demonstrate that astragalin can be effective in allaying ROS-promoted bronchial fibrosis through inhibiting autophagosome formation in airways.

• Authors: In-Hee Cho, Yean-Jung Choi, Ju-Hyun Gong, Daekeun Shin, Min-Kyung Kang, Young-Hee Kang
• Journal: Respiratory research (Respir Res) Vol. 16 Pg. 51 (Apr 21 2015) ISSN: 1465-993X [Electronic] England
• PMID: 25895672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• BECN1 protein, human
• Beclin-1
• Cdh1 Proteins
• Collagen Type I
• Fzr1 protein, mouse
• Kaempferols
• Map1lc3b protein, mouse
• Membrane Proteins
• Microtubule-Associated Proteins
• Reactive Oxygen Species
• Vimentin
• Ovalbumin
• astragalin
• Hydrogen Peroxide
• Spermidine

Topics

• Airway Remodeling (drug effects)
• Animals
• Apoptosis Regulatory Proteins (metabolism)
• Autophagy (drug effects)
• Beclin-1
• Cdh1 Proteins (metabolism)
• Cell Line
• Collagen Type I (metabolism)
• Cytoprotection
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Epithelial Cells (drug effects, metabolism, pathology)
• Epithelial-Mesenchymal Transition (drug effects)
• Humans
• Hydrogen Peroxide (pharmacology)
• Kaempferols (pharmacology)
• Lung (drug effects, pathology)
• Male
• Membrane Proteins (metabolism)
• Mice, Inbred BALB C
• Microtubule-Associated Proteins (metabolism)
• Ovalbumin
• Pulmonary Fibrosis (chemically induced, pathology, prevention & control)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Spermidine (pharmacology)
• Time Factors
• Vimentin (metabolism)