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Bu-Fei Yi-Shen Formula Alleviates Oxidative Stress and Improves Airway Epithelial Barrier Dysfunction in COPD
Gaofeng Li1,2, Ya Li1, Zhengyuan Fan1
1Lung Disease Diagnosis and Treatment Center, National Medical Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450003, People's Republic of China.
Objective:
This study aims to investigate the potential of Bu-Fei Yi-Shen Formula (BYF) in ameliorating airway epithelial barrier dysfunction in chronic obstructive pulmonary disease (COPD) and to elucidate the underlying mechanisms.
Methods:
By establishing both in vivo and in vitro models of COPD, this study examined lung function, lung tissue pathology, inflammatory cytokines levels, cellular apoptosis rate, oxidative stress intensity, and TEER. Concurrently, it quantified the expression levels of proteins relevant to apical junctions, apoptosis, and the Nrf2 signaling pathway. These exhaustive analyses were undertaken to decipher the intricate mechanisms by which BYF ameliorates the disruption of airway epithelial barrier integrity in COPD.
Results:
BYF significantly improved lung function, attenuated lung tissue pathological damage, reduced inflammatory cytokines levels, inhibited cellular apoptosis, upregulated the expression of apical junctional proteins, and alleviated oxidative stress injury in a COPD rat model. In vitro, BYF restored the CSE-induced decreases in TEER values and apical junctional protein expression in BEAS-2B cells, while reducing airway epithelial cell apoptosis apoptosis and oxidative stress injury. Furthermore, BYF counteracted the inhibitory effects of CSE on Nrf2, facilitating the expression of HO-1, a downstream protein of Nrf2. The addition of ML385 exacerbated the apoptosis, oxidative stress, and barrier dysfunction induced by CSE; however, the co-administration of ML385 and BYF reversed the inhibitory effects of ML385.
Conclusion:
These findings underscore that BYF ameliorates airway epithelial barrier dysfunction in COPD by activating the Nrf2/HO-1 signaling pathway.
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