Arctiin-encapsulated DSPE-PEG bubble-like nanoparticles inhibit alveolar epithelial type 2 cell senescence to alleviate pulmonary fibrosis via the p38/p53/p21 pathway

Background: Idiopathic pulmonary fibrosis is a severe and deadly form of diffuse parenchymal lung disease and treatment options are few. Alveolar epithelial type 2 (AEC2) cell senescence is implicated in the pathogenies of IPF. A major bioactive compound from the traditional Chinese medicine Fructus...

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Veröffentlicht in:Frontiers in pharmacology Jg. 14; S. 1141800
Hauptverfasser: Xiong, Dian, Gao, Fei, Shao, Jingbo, Pan, Yueyun, Wang, Song, Wei, Dong, Ye, Shugao, Chen, Yuan, Chen, Rui, Yue, Bingqing, Li, Juan, Chen, Jingyu
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland Frontiers Media S.A 14.03.2023
Schlagworte:
alveolar epithelial type 2 cells
arctiin
cellular senescence
DSPE-PEG
idiopathic pulmonary fibrosis
nanoparticle
Pharmacology
arctiin
DSPE-PEG
cellular senescence
alveolar epithelial type 2 cells
nanoparticle
traditional Chinese medicine
idiopathic pulmonary fibrosis
p38/p53/p21 signaling axis
ISSN:1663-9812, 1663-9812
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Zusammenfassung:Background: Idiopathic pulmonary fibrosis is a severe and deadly form of diffuse parenchymal lung disease and treatment options are few. Alveolar epithelial type 2 (AEC2) cell senescence is implicated in the pathogenies of IPF. A major bioactive compound from the traditional Chinese medicine Fructus arctii , arctiin (ARC) has robust anti-inflammatory, anti-senescence, and anti-fibrosis functions. However, the potential therapeutic effects of ARC on IPF and the underlying mechanisms involved are still unknown. Methods: First of all, ARC was identified as an active ingredient by network pharmacology analysis and enrichment analysis of F. arctii in treating IPF. We developed ARC-encapsulated DSPE-PEG bubble-like nanoparticles (ARC@DPBNPs) to increase ARC hydrophilicity and achieve high pulmonary delivery efficiency. C57BL/6 mice were used to establish a bleomycin (BLM)-induced pulmonary fibrosis model for assessing the treatment effect of ARC@DPBNPs on lung fibrosis and the anti-senescence properties of AEC2. Meanwhile, p38/p53 signaling in AEC2 was detected in IPF lungs, BLM-induced mice, and an A549 senescence model. The effects of ARC@DPBNPs on p38/p53/p21 were assessed in vivo and in vitro . Results: Pulmonary route of administration of ARC@DPBNPs protected mice against BLM-induced pulmonary fibrosis without causing significant damage to the heart, liver, spleen, or kidney. ARC@DPBNPs blocked BLM-induced AEC2 senescence in vivo and in vitro . The p38/p53/p21 signaling axis was significantly activated in the lung tissues of patients with IPF, senescent AEC2, and BLM-induced lung fibrosis. ARC@DPBNPs attenuated AEC2 senescence and pulmonary fibrosis by inhibiting the p38/p53/p21 pathway. Conclusion: Our data suggest that the p38/p53/p21 signaling axis plays a pivotal role in AEC2 senescence in pulmonary fibrosis. The p38/p53/p21 signaling axis inhibition by ARC@DPBNPs provides an innovative approach to treating pulmonary fibrosis in clinical settings.
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Yuan Zeli, Zunyi Medical University, China
These authors have contributed equally to this work
This article was submitted to Respiratory Pharmacology, a section of the journal Frontiers in Pharmacology
Edited by: Wenjun Li, Yantai Institute of Coastal Zone Research (CAS), China
Reviewed by: Pavel Solopov, Old Dominion University, United States
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2023.1141800