Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway

Abstract Background Effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) demonstrates positive effects on stable chronic obstructive pulmonary disease (COPD). Purpose To investigate the mechanisms of ECC-BYF III on COPD rats from the aspect of airway epithelial cell senescence...

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Main Authors: Min-yan Li, Yan-qin Qin, Yan-ge Tian, Kang-chen Li, Brian G. Oliver, Xue-fang Liu, Peng Zhao, Jian-sheng Li
Format: Article
Language:English
Published: BMC 2022-11-01
Series:BMC Pulmonary Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12890-022-02191-9
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author Min-yan Li
Yan-qin Qin
Yan-ge Tian
Kang-chen Li
Brian G. Oliver
Xue-fang Liu
Peng Zhao
Jian-sheng Li
author_facet Min-yan Li
Yan-qin Qin
Yan-ge Tian
Kang-chen Li
Brian G. Oliver
Xue-fang Liu
Peng Zhao
Jian-sheng Li
author_sort Min-yan Li
collection DOAJ
description Abstract Background Effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) demonstrates positive effects on stable chronic obstructive pulmonary disease (COPD). Purpose To investigate the mechanisms of ECC-BYF III on COPD rats from the aspect of airway epithelial cell senescence. Methods COPD model rats (Sprague-Dawley rat) were treated with ECC-BYF III for 8 weeks, and the efficacy was evaluated. Cigarette smoke extract (CSE)-induced senescence model of airway epithelial cells was treated with ECC-BYF III, and related enzymes and proteins involved in oxidative stress and mitophagy were detected. Results ECC-BYF III markedly rescued pulmonary function and histopathological changes, which might be associated with the amelioration of lung senescence, including the reduction of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 levels, increase of the level in total superoxide dismutase (T-SOD), and decease in the p21 level in the airways. Furthermore, ECC-BYF III suppressed p16 and p21 expressions and senescence-associated β-galactosidase (SA-β-Gal) in CSE-induced airway epithelial cells. Moreover, ECC-BYF III upregulated mitophagy-related proteins, including the co-localizations of TOM20 and LC3B, PINK1 and PARK2, and improved mitochondrial function by upregulating mitochondrial mitofusin (MFN)2 and reducing dynamin-related protein 1 (DRP1) expression. ECC-BYF III enhanced the activities of T-SOD and GSH-PX by up-regulating NRF2, thus inhibiting oxidative stress. After intervention with NRF2 inhibitor, the regulation effects of ECC-BYF III on oxidative stress, mitophagy and senescence in airway epithelial cells were significantly suppressed. Conclusions ECC-BYF III exerts beneficial effects on COPD rats by ameliorating airway epithelial cell senescence, which is mediated by inhibiting oxidative stress and subsequently enhancing mitophagy through the activation of NRF2 signaling.
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spelling doaj.art-47e116dc27f64e1c9aa499c27b8b525d2022-12-22T03:46:53ZengBMCBMC Pulmonary Medicine1471-24662022-11-0122111210.1186/s12890-022-02191-9Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathwayMin-yan Li0Yan-qin Qin1Yan-ge Tian2Kang-chen Li3Brian G. Oliver4Xue-fang Liu5Peng Zhao6Jian-sheng Li7Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineAbstract Background Effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) demonstrates positive effects on stable chronic obstructive pulmonary disease (COPD). Purpose To investigate the mechanisms of ECC-BYF III on COPD rats from the aspect of airway epithelial cell senescence. Methods COPD model rats (Sprague-Dawley rat) were treated with ECC-BYF III for 8 weeks, and the efficacy was evaluated. Cigarette smoke extract (CSE)-induced senescence model of airway epithelial cells was treated with ECC-BYF III, and related enzymes and proteins involved in oxidative stress and mitophagy were detected. Results ECC-BYF III markedly rescued pulmonary function and histopathological changes, which might be associated with the amelioration of lung senescence, including the reduction of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 levels, increase of the level in total superoxide dismutase (T-SOD), and decease in the p21 level in the airways. Furthermore, ECC-BYF III suppressed p16 and p21 expressions and senescence-associated β-galactosidase (SA-β-Gal) in CSE-induced airway epithelial cells. Moreover, ECC-BYF III upregulated mitophagy-related proteins, including the co-localizations of TOM20 and LC3B, PINK1 and PARK2, and improved mitochondrial function by upregulating mitochondrial mitofusin (MFN)2 and reducing dynamin-related protein 1 (DRP1) expression. ECC-BYF III enhanced the activities of T-SOD and GSH-PX by up-regulating NRF2, thus inhibiting oxidative stress. After intervention with NRF2 inhibitor, the regulation effects of ECC-BYF III on oxidative stress, mitophagy and senescence in airway epithelial cells were significantly suppressed. Conclusions ECC-BYF III exerts beneficial effects on COPD rats by ameliorating airway epithelial cell senescence, which is mediated by inhibiting oxidative stress and subsequently enhancing mitophagy through the activation of NRF2 signaling.https://doi.org/10.1186/s12890-022-02191-9Chronic obstructive pulmonary diseaseEffective-component compatibility of Bufei Yishen formula IIIAirway epithelial cell senescenceOxidative stressMitophagy
spellingShingle Min-yan Li
Yan-qin Qin
Yan-ge Tian
Kang-chen Li
Brian G. Oliver
Xue-fang Liu
Peng Zhao
Jian-sheng Li
Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway
BMC Pulmonary Medicine
Chronic obstructive pulmonary disease
Effective-component compatibility of Bufei Yishen formula III
Airway epithelial cell senescence
Oxidative stress
Mitophagy
title Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway
title_full Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway
title_fullStr Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway
title_full_unstemmed Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway
title_short Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway
title_sort effective component compatibility of bufei yishen formula iii ameliorated copd by improving airway epithelial cell senescence by promoting mitophagy via the nrf2 pink1 pathway
topic Chronic obstructive pulmonary disease
Effective-component compatibility of Bufei Yishen formula III
Airway epithelial cell senescence
Oxidative stress
Mitophagy
url https://doi.org/10.1186/s12890-022-02191-9
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