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. 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.

Comparative study of cigarette smoke, Klebsiella pneumoniae, and their combination on airway epithelial barrier function in mice

“…BEAS‐2B was cultured in a DMEM medium (12100, Solarbio) containing 10% FBS (S711‐001 S, Lonsrea). The cells were exposed to 10% CS extract, lipopolysaccharide (1 μg/mL, E. coli 055: B5, L2880, Sigma), or a combination of both for 24 h. CS extract was prepared as described in our previous study 16 . To further determine the molecular mechanisms, the cells were treated with AG1478 (2 μM, HY‐13524, MCE) before CS or LPS treatment.…”

Effects of Ipratropium Bromide Combined with Traditional Chinese Medicine Intervention on the Pulmonary Function and Psychological Status of Patients with Chronic Obstructive Pulmonary Disease

“…Traditional Chinese medicine has unique advantages in the treatment of COPD. Clinical practice has confrmed that traditional Chinese medicine nursing has a good efect on relieving symptoms, such as shortness of breath and dyspnea, in patients with chronic respiratory diseases [32,[43][44][45][46][47][48][49]. In this study, patients with COPD were treated with TCM nursing measures, such as emotional nursing, exercise intervention, and acupoint massage, in accordance with the principles of syndrome diferentiation and nursing.…”