Original Articles

Soufeng Yuchuan formula (搜风愈喘方) alleviates asthma airway inflammation and suppresses the progression of asthma by inhibiting ferroptosis in airway epithelial cells

  • Mumu WEI ,
  • Xiaoyu YAN ,
  • Yujing ZHANG ,
  • Xinxin ZHANG ,
  • Yongbin YAN
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  • Department of Paediatrics, the First Affiliated Hospital of Henan University of Chinese Medicine; School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou 450000, China
WEI Mumu and YAN Xiaoyu are co-first authors and contributed equally to this work

Received date: 2024-09-23

  Accepted date: 2025-05-29

  Online published: 2026-01-28

Supported by

Natural Science Foundation-funded Project: the Study on the Mechanism of Soufeng Yuchuan Formula in Regulating Airway Remodeling in Asthmatic Rats Based on Epithelial-Mesenchymal Transition(82174438)

Abstract

OBJECTIVE: To explore whether Soufeng Yuchuan (搜风愈喘, SFYC) formula alleviates asthma by promoting ferroptosis of airway epithelial cells.

METHODS: A chronic asthma rat model was established using ovalbumin (OVA) combined with aluminum hydroxide sensitization and OVA nebulization stimulation. Lung tissue pathology was assessed via hematoxylin and eosin staining and periodic acid-Schiff staining. Lung tissue ultrastructure was observed using transmission electron microscopy. Serum cytokine levels were measured by enzyme-linked immunosorbent assay. Malondialdehyde (MDA), glutathione, and tissue ferrous ion content in rat lung tissues and cells were detected using commercial kits. Immunohistochemical staining was used to determine the expression levels of interleukin-13 (IL-13) and interleukin-6 (IL-6) in lung tissue. Western blotting was employed to detect the expression levels of transferrin receptor 1 (TFR1), transferrin receptor 2 (TFR2), acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11). Cell proliferation, apoptosis and reactive oxygen species (ROS) were evaluated using a cell counting kit-8 assay and flow cytometry. Intracellular lipid peroxidation was detected using a C11-BODIPY 581/591 (C11-BODIPY) probe.

RESULTS: SFYC formula effectively alleviates airway inflammation in asthmatic rats in a dose-dependent manner. It improves airway epithelial cell integrity, reduces alveolar wall thickening and expansion, inhibits goblet cell proliferation and mucus secretion, and decreases the expression of IL-6 and IL-13 in lung tissue, as well as the serum levels of IL-6, IL-13, interleukin-4 (IL-4), and immunoglobulin E (IgE). SFYC formula mitigates ferroptosis in lung tissue of asthmatic rats. At the cellular level, it promotes proliferation of rat airway epithelial cells, inhibits cell apoptosis, suppresses ROS, MDA, and lipid accumulation, reduces the expression of TFR1, TFR2, and ASCL4, and increases the expression of GPX4 and SLC7A11 to mitigate ferroptosis.

CONCLUSION: SFYC formula alleviates asthma airway inflammation by inhibiting ferroptosis in airway epithelial cells, providing new insights and potential therapeutic targets for the development of new asthma treatment drugs.

Cite this article

Mumu WEI , Xiaoyu YAN , Yujing ZHANG , Xinxin ZHANG , Yongbin YAN . Soufeng Yuchuan formula (搜风愈喘方) alleviates asthma airway inflammation and suppresses the progression of asthma by inhibiting ferroptosis in airway epithelial cells[J]. Journal of Traditional Chinese Medicine, 2026 , 46(1) : 73 -84 . DOI: 10.19852/j.cnki.jtcm.2026.01.007

References

1. Ramsahai JM, Hansbro PM, Wark PAB. Mechanisms and management of asthma exacerbations. Am J Respir Crit Care Med 2019; 199: 423-32.
2. Papadopoulos NG, Miligkos M, Xepapadaki P. A current perspective of allergic asthma: from mechanisms to management. Handb Exp Pharmacol 2022; 268: 69-93.
3. Maestrelli P, Boschetto P, Fabbri LM, Mapp CE. Mechanisms of occupational asthma. J Allergy Clin Immunol 2009; 123: 531-42.
4. Cazzola M, Rogliani P, Ora J, Calzetta L, Matera MG. Asthma and comorbidities: recent advances. Pol Arch Intern Med 2022; 132: 16250.
5. Miller RL, Grayson MH, Strothman K. Advances in asthma: New understandings of asthma's natural history, risk factors, underlying mechanisms, and clinical management. J Allergy Clin Immunol 2021; 148: 1430-41.
6. Castillo JR, Peters SP, Busse WW. Asthma exacerbations: pathogenesis, prevention, and treatment. J Allergy Clin Immunol Pract 2017; 5: 918-27.
7. Zhou B, Liu J, Kang R, Klionsky DJ, Kroemer G, Tang D. Ferroptosis is a type of autophagy-dependent cell death. Semin Cancer Biol 2020; 66: 89-100.
8. Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol 2021; 22: 266-82.
9. Liang D, Minikes AM, Jiang X. Ferroptosis at the intersection of lipid metabolism and cellular signaling. Mol Cell 2022; 82: 2215-27.
10. Li J, Cao F, Yin HL, et al. Ferroptosis: past, present and future. Cell Death Dis 2020; 11: 88.
11. Li M, Li M, Hou Y, et al. Ferroptosis triggers airway inflammation in asthma. Ther Adv Respir Dis 2023; 17: 17534666231208628.
12. Wang H, Jia Y, Gu J, Chen O, Yue S. Ferroptosis-related genes are involved in asthma and regulate the immune microenvironment. Front Pharmacol 2023; 14: 1087557.
13. Bao C, Liu C, Liu Q, et al. Liproxstatin-1 alleviates LPS/IL-13-induced bronchial epithelial cell injury and neutrophilic asthma in mice by inhibiting ferroptosis. Int Immunopharmacol 2022; 109: 108770.
14. Yang N, Shang Y. Ferrostatin-1 and 3-methyladenine ameliorate ferroptosis in ova-Induced asthma model and in IL-13-challenged BEAS-2B Cells. Oxid Med Cell Longev 2022; 2022: 9657933.
15. Zhang Y, Chen Y, Wu Y, et al. Scorpio and centipede ameliorate asthma by inhibiting the crosstalk between ferroptosis and inflammation in airway epithelial cells. Iran J Basic Med Sci 2023; 26: 1438-43.
16. Lü X, Dong M, Tang W, et al. Ferroptosis, novel therapeutics in asthma. Biomed Pharmacother 2022; 153: 113516.
17. Chou MC, Jou IM, Chen HT, Chang R. Traditional Chinese Medicine use may reduce medical utility in patients with asthma: correspondence. QJM 2023; 116: 256.
18. Wang MH, Chen C, Yeh ML, Lin JG. Using traditional chinese medicine to relieve asthma symptoms: a systematic review and Meta-analysis. Am J Chin Med 2019; 47: 1659-74.
19. Chen T, Ding L, Zhao M, et al. Recent advances in the potential effects of natural products from Traditional Chinese Medicine against respiratory diseases targeting ferroptosis. Chin Med 2024; 19: 49.
20. Sun B, Cai F, Yu L, An R, Wei B, Li M. Quercetin inhibits ferroptosis through the SIRT1/Nrf2/HO-1 signaling pathway and alleviates asthma disease. Transl Pediatr 2024; 13: 1747-59.
21. Jiang L, Xu L, Liu H, Chen H, Wang W. Rhizoma Dioscoreae Nipponicae relieves asthma by inducing the ferroptosis of eosinophils and inhibiting the p38 MAPK signaling pathway. Crit Rev Immunol 2024; 44: 77-87.
22. Yan Y, Liu L, Dou Z, Xu Y, Yan X. Soufeng Yuchuan decoction mitigates the ovalbumin-induced lung damage in a rat model of asthma. Biomed Pharmacother 2020; 125: 109933.
23. Xu SY. Pharmacology laboratory methodology. Beijing: People's Medical Publishing House, 1982: 1-1721.
24. Cui FM, Su SB, Nie JH, Li BY, Tong J. A method for isolating, identifying and culturing of rat trachea-bronchia epithelial cells. Zhong Guo Fu She Wei Sheng 2005; 14: 246-7.
25. Agache I, Eguiluz-Gracia I, Cojanu C, et al. Advances and highlights in asthma in 2021. Allergy 2021; 76: 3390-407.
26. Chung KF, Dixey P, Abubakar-Waziri H, et al. Characteristics, phenotypes, mechanisms and management of severe asthma. Chin Med J (Engl) 2022; 135: 1141-55.
27. Wang Y, Wan R, Peng W, Zhao X, Bai W, Hu C. Quercetin alleviates ferroptosis accompanied by reducing M1 macrophage polarization during neutrophilic airway inflammation. Eur J Pharmacol 2023; 938: 175407.
28. Han F, Li S, Yang Y, Bai Z. Interleukin-6 promotes ferroptosis in bronchial epithelial cells by inducing reactive oxygen species-dependent lipid peroxidation and disrupting iron homeostasis. Bioengineered 2021; 12: 5279-88.
29. Zeng F, Nijiati S, Tang L, Ye J, Zhou Z, Chen X. Ferroptosis detection: from approaches to applications. Angew Chem Int Ed Engl 2023; 62: e202300379.
30. Pope LE, Dixon SJ. Regulation of ferroptosis by lipid metabolism. Trends Cell Biol 2023; 33: 1077-87.
31. Liu J, Kang R, Tang D. Signaling pathways and defense mechanisms of ferroptosis. FEBS J 2022; 289: 7038-50.
32. Lin L, Hu X, Li Q, Huang L. Methyltransferase-like 3 (METTL3) epigenetically modulates glutathione peroxidase 4 (GPX4) expression to affect asthma. Iran J Allergy Asthma Immunol 2023; 22: 551-60.
33. Zheng Y, Fan J, Jiang X. The role of ferroptosis-related genes in airway epithelial cells of asthmatic patients based on bioinformatics. Medicine (Baltimore) 2023; 102: e33119.
34. Xing Y, Feng L, Dong Y, et al. Exploration and validation of potential biomarkers and therapeutic targets in ferroptosis of asthma. J Asthma Allergy 2023; 16: 689-710.
35. Song J, Zhang H, Tong Y, et al. Molecular mechanism of interleukin-17A regulating airway epithelial cell ferroptosis based on allergic asthma airway inflammation. Redox Biol 2023; 68: 102970.
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