Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Pseudoephedrine Improves Chronic Obstructive Pulmonary Disease by Regulating Airway Senescence and Mitochondrial Function through PI3K/AKT/mTOR Axis

  • Lijuan Wu (Emergency Department, The First Affiliated Hospital of Hebei University of Chinese Medicine) ;
  • Fenqiao Chen (Emergency Department of Hebei Provincial Hospital of Chinese Medicine) ;
  • He Zhang (Emergency Department of Hebei Provincial Hospital of Chinese Medicine) ;
  • Wenzhong Xu (Emergency Department of Hebei Provincial Hospital of Chinese Medicine) ;
  • Tan'e Liu (Emergency Department of Hebei Provincial Hospital of Chinese Medicine) ;
  • Ming Liu (Department of Respiratory and Critical Care Medicine II, Hebei Provincial Hospital of Chinese Medicine) ;
  • Lianxing Liu (Telemedicine Center, Hebei Provincial Hospital of Chinese Medicine) ;
  • Jianqiang Mei (Emergency Department, The First Affiliated Hospital of Hebei University of Chinese Medicine)
  • Received : 2025.09.24
  • Accepted : 2026.03.26
  • Published : 2026.05.01
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Abstract

Ephedra can improve chronic obstructive pulmonary disease (COPD). Pseudoephedrine (PSE) is a main active ingredients of ephedra. It has anti-inflammatory pharmacological properties. Its effect on COPD and its possible mechanism have not been elucidated. The COPD rat model was constructed by systemic cigarette smoke exposure combined with lipopolysaccharide (LPS) tracheal instillation. BEAS-2B cells were treated using cigarette smoke extract; PSE was administered for treatment. The senescence level of rat lung tissue and bronchial epithelial cells was evaluated through staining, immunofluorescence and western blot. The mitochondrial damage of rats and BEAS-2B cells was detected by transmission electron microscopy, JC-1 probe, MitoSOX Red probe and kits. In addition, the lung function indexes of rats were detected by animal lung function analysis system. Hematoxylin and eosin (HE) staining analyzed the pathological damage. Enzyme-linked immunosorbent assay (ELISA), kit and immunohistochemistry were used to evaluate inflammation and oxidative stress. Western blot detected phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) axis protein. PSE significantly reduced senescent cells, apoptosis rate and P21 level in rat lung tissue and BEAS-2B cells, significantly increased the levels of zonula occludens-1 (ZO-1) and adenosine triphosphate (ATP), restored mitochondrial structure, and visible mitochondrial cristae. It also inhibited reactive oxygen species (ROS) levels and mitochondrial excessive fission. PSE also significantly improved lung function in rats, increased mean alveolar number (MAN), reduced pro-inflammatory factors, and increased superoxide dismutase (SOD) levels. PSE markedly suppressed p-p85, p-AKT and p-mTOR protein expressions. In addition, the PI3K/AKT agonist 740Y-P weakened the effect of PSE on improving COPD. PSE inhibited PI3K/AKT/mTOR axis, improved lung tissue senescence, mitochondrial dysfunction and pathological damage, and reduced airway inflammation and oxidative stress damage, thereby alleviating COPD.

Keywords

Acknowledgement

This study was supported by The Project of Outstanding Talents in Clinical Medicine Funded by the Hebei Provincial Government (ZF2025301, ZF2025303).

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