2. Academic Validation
  3. Scutellarein from Erigeron breviscapus Inhibits Apoptosis-Mediated Epithelial Barrier Disruption and Alleviates Cigarette Smoke-Induced Lung Injury

Scutellarein from Erigeron breviscapus Inhibits Apoptosis-Mediated Epithelial Barrier Disruption and Alleviates Cigarette Smoke-Induced Lung Injury

  • Pharmaceuticals (Basel). 2026 Jan 8;19(1):113. doi: 10.3390/ph19010113.
Chuchu Xi 1 2,  Hongrong Fu 1 2,  Xu Qin 1 2,  Yujing Wang 1 2,  Kerui Ren 1 2,  Mengmeng Song 1 2,  Huaduan Liang 1 2,  Fang Zhao 2,  Zhengyu Cao 1 2
Affiliations

Affiliations

  • 1 Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, China Pharmaceutical University, Nanjing 211198, China.
  • 2 Department of TCM Pharmacology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
PMID: 41599711 DOI: 10.3390/ph19010113
Abstract

Background/Objectives: Cigarette smoke (CS) drives pathogenesis across the spectrum of chronic respiratory disorders, exerting its detrimental effects primarily through oxidative stress and programmed cell death. Scutellarein (Scu), a botanical-origin flavonoid enriched in respiratory therapeutics-oriented Chinese medicinal herbs, demonstrates established anti-inflammatory applications. This study systematically evaluated the protective roles of Scu against CS-induced lung injury and explored the underlying mechanisms. Methods: Subacute CS-exposed mice were used to evaluate the therapeutic effects of Scu on lung injury. Immunofluorescence and quantitative PCR were used to examine the expression levels of junctional proteins and proinflammatory mediators. Apoptotic cell death was quantified using Annexin V-FITC/7-AAD staining. Transepithelial electrical resistance and dextran permeability assay were used to access the barrier integrity in alveolar epithelial MLE-12 cells. Western blotting was used to detect the changes in the signal pathway. Results: In CS-exposed mice, Scu administration dose-dependently reduced histopathological scores, pulmonary edema, changes in the alveolar structure, and inflammatory cell infiltration. In MLE-12 cells, Scu significantly suppressed cigarette smoke condensate (CSC)-induced inflammatory mediators, oxidative stress, Caspase-3 activation, and Apoptosis and preserved CSC-suppressed tight junction protein expression and barrier disruption. Scu also rescued CSC-altered expression levels of Hrk, Ecscr, and Myo5b and mitigated the CSC-suppressed PI3K/Akt/mTOR pathway. Conclusions: Scu alleviates CS-induced subacute lung injury through its antioxidant, anti-apoptotic effects to maintain epithelial barrier integrity likely via the mitigation of the CSC-suppressed PI3K/Akt/mTOR pathway.

Keywords

apoptosis; cigarette smoke; epithelial barrier; lung injury; scutellarein.

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