Effective-Component Compatibility of Bufei Yishen Formula III Protects Lung Air-Blood Barrier by Regulating the Oxidative Stress: via the Nuclear Factor-E2-Related Factor 2 Pathway

Int J Chron Obstruct Pulmon Dis. 2025 Jul 4:20:2211-2226. doi: 10.2147/COPD.S513071. eCollection 2025.

Abstract

Purpose: Bufei Yishen formula (BYF) is an effective treatment strategy for chronic obstructive pulmonary disease (COPD). Effective-component compatibility of BYF III (ECC-BYF III), composed of 5 active ingredients (ginsenoside Rh1, paeonol, astragaloside, icariin and nobiletin) from BYF, has similar effects to BYF in intervening COPD. The abnormal structure and hypofunction of lung air-blood barrier induces inefficiency gas exchange and promotes development of COPD. However, the role of ECC-BYF III in the air-blood barrier remains unknown. This study dedicated to exploring the effect and mechanism of ECC-BYF III improve structure and function of lung air-blood barrier in COPD.

Methods: A COPD rat model was established to study the treatment of ECC-BYF III against COPD. The protective effect of ECC-BYF III on COPD was evaluated through pulmonary function and lung tissue pathology. The structure damage of the lung air-blood barrier was assessed using electron microscopy and immunofluorescence. Finally, we proved the regulating effect of ECC-BYF III in oxidative via the Nrf2 pathway.

Results: The ECC-BYF III could significantly alleviate reduced pulmonary function, decrease damage of lung tissue and regulate oxidative stress in COPD rats. And ECC-BYF III reduced thickness of respiratory membrane, ameliorated damage of pulmonary capillary endothelial cells (PCECs) and alveolar epithelial cells (AECs) in COPD rats. Also, ECC-BYF III protected the function and normal cell morphology of type I alveolar epithelial cell (AT I) and type II alveolar epithelial cell (AT II) in COPD rats. Lastly, ECC-BYF III was indicated to adjust the Nrf2 pathway to improve oxidative stress and protect lung air-blood barrier in COPD rats.

Conclusion: ECC-BYF III protects lung air-blood barrier in COPD by regulating oxidative stress via Nrf2 pathway.

Keywords: Nrf2 pathway; chronic obstructive pulmonary disease; effective-component compatibility of bufei yishen formula III; lung air-blood barrier; oxidative stress.

MeSH terms

  • Animals
  • Antioxidants* / pharmacology
  • Blood-Air Barrier* / drug effects
  • Blood-Air Barrier* / metabolism
  • Blood-Air Barrier* / pathology
  • Blood-Air Barrier* / physiopathology
  • Blood-Air Barrier* / ultrastructure
  • Disease Models, Animal
  • Drugs, Chinese Herbal* / pharmacology
  • Lung* / blood supply
  • Lung* / drug effects
  • Lung* / metabolism
  • Lung* / pathology
  • Lung* / physiopathology
  • Male
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress* / drug effects
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / metabolism
  • Pulmonary Disease, Chronic Obstructive* / pathology
  • Pulmonary Disease, Chronic Obstructive* / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction

Substances

  • NF-E2-Related Factor 2
  • Drugs, Chinese Herbal
  • Nfe2l2 protein, rat
  • Antioxidants