GAO Yuchen,ZHU Hongyu,XIA Heyue,et al.Discussion on the Role of Ferroptosis in Chronic Obstructive Pulmonary Disease from the Perspective of "Qi Deficiency with Retention and Stagnation"[J].Journal of Traditional Chinese Medicine,2026,67(11):1167-1172.
GAO Yuchen,ZHU Hongyu,XIA Heyue,et al.Discussion on the Role of Ferroptosis in Chronic Obstructive Pulmonary Disease from the Perspective of "Qi Deficiency with Retention and Stagnation"[J].Journal of Traditional Chinese Medicine,2026,67(11):1167-1172.DOI: 10.13288/j.11-2166/r.2026.11.007.
Discussion on the Role of Ferroptosis in Chronic Obstructive Pulmonary Disease from the Perspective of "Qi Deficiency with Retention and Stagnation"
Ferroptosis is a key driver of the onset and progression of chronic obstructive pulmonary disease (COPD). By exploring the role of ferroptosis in COPD from the perspective of "
qi
deficiency with retention and stagnation", it is considered that mitochondrial dysfunction and imbalanced antioxidant defenses are the microscopic manifestations of "
qi
deficiency", whereas iron accumulation and lipid peroxide deposition constitute the pathological basis of "retention and stagnation". In traditional Chinese medicine (TCM), the treatment principle is tonifying deficiency and benefiting
qi
, scattering retention and unblocking stagnation. Its mechanism involves improving the antioxidant system and mitochondrial function to enhance cellular resistance to ferroptosis, as well as relieving pulmonary iron overload, excessive lipid peroxidation, and inflammatory factor release to reduce the accumulation of pathological products, thereby exerting therapeutic effects on COPD.
DE OCA M M , PEREZ-PADILLA R , CELLI B , et al . The global burden of COPD: epidemiology and effect of prevention strategies [J]. Lancet Respir Med , 2025 , 13 ( 8 ): 709 - 724 .
GÜNES GÜNSEL G , CONLON T M , JERIDI A , et al . The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD [J]. Nat Commun , 2022 , 13 ( 1 ): 1303 .
MUSSALO-RAUHAMAA H , LEPPÄNEN A , SALMELA S S , et al . Cigarettes as a source of some trace and heavy metals and pesticides in man [J]. Arch Environ Health , 1986 , 41 ( 1 ): 49 - 55 .
GHIO A J , HILBORN E D , STONEHUERNER J G , et al . Particulate matter in cigarette smoke alters iron homeostasis to produce a biological effect [J]. Am J Respir Crit Care Med , 2008 , 178 ( 11 ): 1130 - 1138 .
LI Y , YANG Y , GUO T , et al . Heme oxygenase-1 determines the cell fate of ferroptotic death of alveolar macrophages in COPD [J]. Front Immunol , 2023 , 14 : 1162087 . doi: 10.3389/fimmu.2023.1162087 http://dx.doi.org/10.3389/fimmu.2023.1162087 .
CLOONAN S M , GLASS K , LAUCHO-CONTRERAS M E , et al . Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice [J]. Nat Med , 2016 , 22 ( 2 ): 163 - 174 .
SWENSON S A , MOORE C M , MARCERO J R , et al . From synthesis to utilization: the ins and outs of mitochondrial heme [J]. Cells , 2020 , 9 ( 3 ): 579 .
WANG Y , XIA S . Relationship between ACSL4-mediated ferroptosis and chronic obstructive pulmonary disease [J]. Int J Chron Obstruct Pulmon Dis , 2023 , 18 : 99 - 111 . doi: 10.2147/COPD.S391129 http://dx.doi.org/10.2147/COPD.S391129 .
CHEN X , KANG R , KROEMER G , et al . Ferroptosis in infection, inflammation, and immunity [J]. J Exp Med , 2021 , 218 ( 6 ): e20210518 .
HU Y , HUANG Y , ZONG L , et al . Emerging roles of ferroptosis in pulmonary fibrosis: current perspectives, opportunities and challenges [J]. Cell Death Discov , 2024 , 10 ( 1 ): 301 .
YOSHIDA M , MINAGAWA S , ARAYA J , et al . Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis [J]. Nat Commun , 2019 , 10 ( 1 ): 3145 .
CHEN Y , FANG Z M , YI X , et al . The interaction between ferroptosis and inflammatory signaling pathways [J]. Cell Death Dis , 2023 , 14 ( 3 ): 205 .
GENCER M , AKSOY N , DAGLI E C , et al . Prolidase activity dysregulation and its correlation with oxidative-antioxidative status in chronic obstructive pulmonary disease [J]. J Clin Lab Anal , 2011 , 25 ( 1 ): 8 - 13 .
GĘGOTEK A , SKRZYDLEWSKA E . Biological effect of protein modifications by lipidperoxidation products [J]. Chem Phys Lipids , 2019 , 221 : 46 - 52 . doi: 10.1016/j.chemphyslip.2019.03.011 http://dx.doi.org/10.1016/j.chemphyslip.2019.03.011 .
LILL R , FREIBERT S A . Mechanisms of mitochondrial iron-sulfur protein biogenesis [J]. Annu Rev Biochem , 2020 , 89 : 471 - 499 . doi: 10.1146/annurev-biochem-013118-111540 http://dx.doi.org/10.1146/annurev-biochem-013118-111540 .
D'ARCY M S . Mitophagy in health and disease. Molecular mechanisms, regulatory pathways, and therapeutic implications [J]. Apoptosis , 2024 , 29 ( 9/10 ): 1415 - 1428 .
MENG T , LI F S , XU D , et al . Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease [J]. J Thorac Dis , 2024 , 16 ( 4 ): 2326 - 2340 .
LIU Y , LU S , WU L L , et al . The diversified role of mitochondria in ferroptosis in cancer [J]. Cell Death Dis , 2023 , 14 ( 8 ): 519 .
LIU M J , XU Z P , GUAN Y Q , et al . Ethyl acetate fraction of Thesium chinense Turcz. alleviates chronic obstructive pulmonary disease through inhibition of ferroptosis mediated by activating Nrf2/SLC7A11/GPX4 axis [J]. J Ethnopharmacol , 2025 , 337 ( Pt 1 ): 118776 .
TANG X , LI Z , YU Z , et al . Effect of curcumin on lung epithelial injury and ferroptosis induced by cigarette smoke [J]. Hum Exp Toxicol , 2021 , 40 ( 12 suppl ): S753 - S762 .
LIU L , WEN T , XIAO Y , et al . Sea buckthorn extract mitigates chronic obstructive pulmonary disease by suppression of ferroptosis via scavenging ROS and blocking p53/MAPK pathways [J]. J Ethnopharmacol , 2025 , 336 : 118726 . doi: 10.1016/j.jep.2024.118776 http://dx.doi.org/10.1016/j.jep.2024.118776 .
LI X , ZHENG W , LUO Z , et al . Elucidating the underlying therapeutic mechanism of Feikang prescription on chronic obstructive pulmonary disease: insights from a comprehensive analysis [J]. Phytomedicine , 2025 , 147 : 157175 . doi: 10.1016/j.phymed.2025.157175 http://dx.doi.org/10.1016/j.phymed.2025.157175 .
LIU L , ZHANG Y , WANG L , et al . Scutellarein alleviates chronic obstructive pulmonary disease through inhibition of ferroptosis by chelating iron and interacting with arachidonate 15-lipoxygenase [J]. Phytother Res , 2023 , 37 ( 10 ): 4587 - 4606 .
TAN W , LIANG Z , TAN X , et al . Ginsenoside Rg1 improves cigarette smoke-induced ferroptosis in COPD by regulating PERK/ATF4 axis to inhibit endoplasmic reticulum stress [J]. Biochem Biophys Res Commun , 2024 , 739 : 150946 . doi: 10.1016/j.bbrc.2024.150946 http://dx.doi.org/10.1016/j.bbrc.2024.150946 .
CALIRI A W , TOMMASI S , BESARATINIA A . Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer [J]. Mutat Res Rev Mutat Res , 2021 , 787 : 108365 . doi: 10.1016/j.mrrev. 2021.108365 http://dx.doi.org/10.1016/j.mrrev.2021.108365 .
LEI T , LU T , YU H , et al . Efficacy of Vitamin C supplementation on chronic obstructive pulmonary disease (copd): a systematic review and meta-analysis [J]. Int J Chron Obstruct Pulmon Dis , 2022 , 17 : 2201 - 2216 . doi: 10.2147/COPD.S368645 http://dx.doi.org/10.2147/COPD.S368645 .
ZHU M , PENG L , HUO S , et al . STAT3 signaling promotes cardiac injury by upregulating NCOA4-mediated ferritinophagy and ferroptosis in high-fat-diet fed mice [J]. Free Radic Biol Med , 2023 , 201 : 111 - 125 . doi: 10.1016/j.freeradbiomed.2023.03.003 http://dx.doi.org/10.1016/j.freeradbiomed.2023.03.003 .
CHEN Z , JIANG J , FU N , et al . Targetting ferroptosis for blood cell-related diseases [J]. J Drug Target , 2022 , 30 ( 3 ): 244 - 258 .
CHEN H , WU H , WANG Q , et al . IFIT2 mediates iron retention and cholesterol efflux in atherosclerosis [J]. Int Immunopharmacol , 2024 , 142 ( Pt A ): 113131 .
XIE J , LIU M , GAO Y , et al . Integration of metabolomics and network pharmacology to reveal the protective mechanism underlying Qibai Pingfei capsule on chronic obstructive pulmonary disease [J]. Front Pharmacol , 2023 , 14 : 1258138 . doi: 10.3389/fphar.2023.1258138 http://dx.doi.org/10.3389/fphar.2023.1258138 .
XU A , XU Y , CHEN H , et al . Ginkgo biloba extract alleviates ferroptosis in lung epithelial cells induced by cigarette smoke extract through miR-3,619-5p/GPX4 axis [J]. Toxicol Res (Camb) , 2025 , 14 ( 1 ): tfae225 .
ZHENG M , HUANG L , YUAN H , et al . Investigating the mechanism of Qifenggubiao granules in COPD treatment: an integrated exploration of ferroptosis and the Gut-Lung Axis [J]. Biomater Res , 2025 , 29 : 0263 . doi: 10.34133/bmr.0263 http://dx.doi.org/10.34133/bmr.0263 .
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