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Emodin alleviates radiation-induced pulmonary fibrosis by targeting cellular senescence via the mtDNA-cGAS-STING axis.

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Τίτλος: Emodin alleviates radiation-induced pulmonary fibrosis by targeting cellular senescence via the mtDNA-cGAS-STING axis.
Συγγραφείς: Duan W; Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, People's Republic of China., Sha Y; 920th Hospital of Joint Logistics Support Force, PLA, Kunming, Yunnan, People's Republic of China., Tang X; Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, People's Republic of China., Liu R; Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, People's Republic of China., Su B; 920th Hospital of Joint Logistics Support Force, PLA, Kunming, Yunnan, People's Republic of China., Huang M; 920th Hospital of Joint Logistics Support Force, PLA, Kunming, Yunnan, People's Republic of China., Xun X; 920th Hospital of Joint Logistics Support Force, PLA, Kunming, Yunnan, People's Republic of China., Ye Y; 920th Hospital of Joint Logistics Support Force, PLA, Kunming, Yunnan, People's Republic of China. ye_yfei@163.com.
Πηγή: Biogerontology [Biogerontology] 2026 Jul 06; Vol. 27 (4). Date of Electronic Publication: 2026 Jul 06.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Kluwer Academic Country of Publication: Netherlands NLM ID: 100930043 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-6768 (Electronic) Linking ISSN: 13895729 NLM ISO Abbreviation: Biogerontology Subsets: MEDLINE
Imprint Name(s): Original Publication: Dordrecht ; Boston : Kluwer Academic, c2000-
Ιατρικοί όροι (MeSH): Cellular Senescence*/drug effects , Cellular Senescence*/radiation effects , Emodin*/pharmacology , DNA, Mitochondrial*/metabolism , Membrane Proteins*/metabolism , Nucleotidyltransferases*/metabolism , Pulmonary Fibrosis*/drug therapy , Pulmonary Fibrosis*/etiology , Pulmonary Fibrosis*/metabolism , Radiation Pneumonitis*/pathology , Radiation Pneumonitis*/metabolism , Radiation Pneumonitis*/drug therapy, Signal Transduction/drug effects ; Mitochondria/drug effects ; Mitochondria/metabolism ; Animals ; cGAS-STING Signaling Pathway ; STING Protein ; Mice ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; Mice, Inbred C57BL ; Male
Περίληψη: Radiation-induced pulmonary fibrosis (RIPF) is a severe complication of thoracic radiotherapy with limited effective treatment options. Cellular senescence has emerged as a critical driver of age-related tissue fibrosis; however, its role in RIPF and potential as a therapeutic target are underexplored. In this study, we investigated whether emodin, a natural compound with known anti-aging properties, alleviates RIPF by suppressing radiation-induced cellular senescence. In a mouse model exposed to 16 Gy thoracic irradiation, emodin treatment significantly attenuated pulmonary fibrosis, reduced collagen deposition, and downregulated fibrotic markers. Notably, emodin markedly suppressed radiation-induced senescence in pulmonary epithelial cells, accompanied by reduced secretion of senescence-associated secretory phenotype (SASP) factors. Mechanistically, emodin preserved mitochondrial integrity, curbed mitochondrial reactive oxygen species (mtROS) accumulation, and prevented mitochondrial DNA (mtDNA) leakage into the cytoplasm, thereby inhibiting the cGAS-STING-NF-κB signaling pathway, a key pro-inflammatory axis in senescent cells. Importantly, knockdown of cGAS or treatment with the mitochondrial uncoupler CCCP attenuated the anti-senescent effects of emodin, underscoring the centrality of mitochondrial dysfunction and the mtDNA-cGAS-STING axis in senescence-driven fibrosis. Collectively, these findings identify emodin as a novel senescence-targeting agent that mitigates RIPF by alleviating mitochondrial dysfunction and disrupting the mtDNA-cGAS-STING pathway, highlighting its therapeutic potential in age-related fibrotic diseases.
(© 2026. The Author(s), under exclusive licence to Springer Nature B.V.)
Competing Interests: Declarations. Competing Interests: The authors declare no competing interests. Ethical approval: The study protocol was approved by the Ethics Committee of Jingzhou Hospital Affiliated to Yangtze University. All animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of the university.
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Algieri C et al (2025) Mitochondrial dysfunction acts as a modulator of the immunometabolic route for activating the cytosolic DNA sensor pathway in triggering innate immunosurveillance. J Transl Med 23(1):1321. https://doi.org/10.1186/s12967-025-07392-4. (PMID: 10.1186/s12967-025-07392-44125782812628636)
Alipour-Khezri E et al (2025) Cytosolic DNA sensing pathway in senescence and aging: underlying mechanisms and targeted interventions. Biomed Pharmacother 193:118790. https://doi.org/10.1016/j.biopha.2025.118790. (PMID: 10.1016/j.biopha.2025.11879041273929)
Bryant JD et al (2022) Assessing mitochondrial DNA release into the cytosol and subsequent activation of innate immune-related pathways in mammalian cells. Curr Protoc 2(2):e372. Erratum in: Curr Protoc 4(7):e1106. https://doi.org/10.1002/cpz1.372.
Bai J et al (2020) Emodin, a natural anthraquinone, suppresses liver cancer in vitro and in vivo by regulating VEGFR2 and miR-34a. Invest New Drugs 38(2):229–245. https://doi.org/10.1007/s10637-019-00777-5. (PMID: 10.1007/s10637-019-00777-530976957)
Blasiak J (2020) Senescence in the pathogenesis of age-related macular degeneration. Cell Mol Life Sci 77(5):789–805. https://doi.org/10.1007/s00018-019-03420-x. (PMID: 10.1007/s00018-019-03420-x3189754311105088)
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Grant Information: chmdf2025-xrky11-05 Medical Research Projects of China Medical and Health Development Foundation; JM2025110199 Beijing Chen Jumei Public Welfare Foundation
Contributed Indexing: Keywords: CGAS–STING pathway; Cellular senescence; Emodin; Mitochondrial dysfunction; RIPF
Substance Nomenclature: KA46RNI6HN (Emodin)
0 (DNA, Mitochondrial)
0 (STING Protein)
EC 2.7.7.86 (Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase)
0 (Membrane Proteins)
EC 2.7.7.- (Nucleotidyltransferases)
EC 2.7.7.- (cGAS protein, mouse)
0 (Sting1 protein, mouse)
Entry Date(s): Date Created: 20260706 Date Completed: 20260706 Latest Revision: 20260706
Update Code: 20260706
DOI: 10.1007/s10522-026-10472-7
PMID: 42405973
Βάση Δεδομένων: MEDLINE
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  Data: Emodin alleviates radiation-induced pulmonary fibrosis by targeting cellular senescence via the mtDNA-cGAS-STING axis.
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  Data: <searchLink fieldCode="AU" term="%22Duan+W%22">Duan W</searchLink>; Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, People's Republic of China.<br /><searchLink fieldCode="AU" term="%22Sha+Y%22">Sha Y</searchLink>; 920th Hospital of Joint Logistics Support Force, PLA, Kunming, Yunnan, People's Republic of China.<br /><searchLink fieldCode="AU" term="%22Tang+X%22">Tang X</searchLink>; Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, People's Republic of China.<br /><searchLink fieldCode="AU" term="%22Liu+R%22">Liu R</searchLink>; Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, People's Republic of China.<br /><searchLink fieldCode="AU" term="%22Su+B%22">Su B</searchLink>; 920th Hospital of Joint Logistics Support Force, PLA, Kunming, Yunnan, People's Republic of China.<br /><searchLink fieldCode="AU" term="%22Huang+M%22">Huang M</searchLink>; 920th Hospital of Joint Logistics Support Force, PLA, Kunming, Yunnan, People's Republic of China.<br /><searchLink fieldCode="AU" term="%22Xun+X%22">Xun X</searchLink>; 920th Hospital of Joint Logistics Support Force, PLA, Kunming, Yunnan, People's Republic of China.<br /><searchLink fieldCode="AU" term="%22Ye+Y%22">Ye Y</searchLink>; 920th Hospital of Joint Logistics Support Force, PLA, Kunming, Yunnan, People's Republic of China. ye_yfei@163.com.
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  Data: <searchLink fieldCode="JN" term="%22100930043%22">Biogerontology</searchLink> [Biogerontology] 2026 Jul 06; Vol. 27 (4). <i>Date of Electronic Publication: </i>2026 Jul 06.
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  Data: <i>Original Publication</i>: Dordrecht ; Boston : Kluwer Academic, c2000-
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  Data: <searchLink fieldCode="MM" term="%22Cellular+Senescence%22">Cellular Senescence*</searchLink>/<searchLink fieldCode="MM" term="%22Cellular+Senescence+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Cellular+Senescence%22">Cellular Senescence*</searchLink>/<searchLink fieldCode="MM" term="%22Cellular+Senescence+radiation+effects%22">radiation effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Emodin%22">Emodin*</searchLink>/<searchLink fieldCode="MM" term="%22Emodin+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22DNA%2C+Mitochondrial%22">DNA, Mitochondrial*</searchLink>/<searchLink fieldCode="MM" term="%22DNA%2C+Mitochondrial+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Membrane+Proteins%22">Membrane Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Membrane+Proteins+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Nucleotidyltransferases%22">Nucleotidyltransferases*</searchLink>/<searchLink fieldCode="MM" term="%22Nucleotidyltransferases+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Pulmonary+Fibrosis%22">Pulmonary Fibrosis*</searchLink>/<searchLink fieldCode="MM" term="%22Pulmonary+Fibrosis+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Pulmonary+Fibrosis%22">Pulmonary Fibrosis*</searchLink>/<searchLink fieldCode="MM" term="%22Pulmonary+Fibrosis+etiology%22">etiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Pulmonary+Fibrosis%22">Pulmonary Fibrosis*</searchLink>/<searchLink fieldCode="MM" term="%22Pulmonary+Fibrosis+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Radiation+Pneumonitis%22">Radiation Pneumonitis*</searchLink>/<searchLink fieldCode="MM" term="%22Radiation+Pneumonitis+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Radiation+Pneumonitis%22">Radiation Pneumonitis*</searchLink>/<searchLink fieldCode="MM" term="%22Radiation+Pneumonitis+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Radiation+Pneumonitis%22">Radiation Pneumonitis*</searchLink>/<searchLink fieldCode="MM" term="%22Radiation+Pneumonitis+drug+therapy%22">drug therapy</searchLink><br /><searchLink fieldCode="MH" term="%22Signal+Transduction%22">Signal Transduction</searchLink>/<searchLink fieldCode="MH" term="%22Signal+Transduction+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Mitochondria%22">Mitochondria</searchLink>/<searchLink fieldCode="MH" term="%22Mitochondria+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Mitochondria%22">Mitochondria</searchLink>/<searchLink fieldCode="MH" term="%22Mitochondria+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22cGAS-STING+Signaling+Pathway%22">cGAS-STING Signaling Pathway</searchLink> ; <searchLink fieldCode="MH" term="%22STING+Protein%22">STING Protein</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Cyclic+Guanosine+Monophosphate-Adenosine+Monophosphate+Synthase%22">Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%2C+Inbred+C57BL%22">Mice, Inbred C57BL</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Radiation-induced pulmonary fibrosis (RIPF) is a severe complication of thoracic radiotherapy with limited effective treatment options. Cellular senescence has emerged as a critical driver of age-related tissue fibrosis; however, its role in RIPF and potential as a therapeutic target are underexplored. In this study, we investigated whether emodin, a natural compound with known anti-aging properties, alleviates RIPF by suppressing radiation-induced cellular senescence. In a mouse model exposed to 16 Gy thoracic irradiation, emodin treatment significantly attenuated pulmonary fibrosis, reduced collagen deposition, and downregulated fibrotic markers. Notably, emodin markedly suppressed radiation-induced senescence in pulmonary epithelial cells, accompanied by reduced secretion of senescence-associated secretory phenotype (SASP) factors. Mechanistically, emodin preserved mitochondrial integrity, curbed mitochondrial reactive oxygen species (mtROS) accumulation, and prevented mitochondrial DNA (mtDNA) leakage into the cytoplasm, thereby inhibiting the cGAS-STING-NF-κB signaling pathway, a key pro-inflammatory axis in senescent cells. Importantly, knockdown of cGAS or treatment with the mitochondrial uncoupler CCCP attenuated the anti-senescent effects of emodin, underscoring the centrality of mitochondrial dysfunction and the mtDNA-cGAS-STING axis in senescence-driven fibrosis. Collectively, these findings identify emodin as a novel senescence-targeting agent that mitigates RIPF by alleviating mitochondrial dysfunction and disrupting the mtDNA-cGAS-STING pathway, highlighting its therapeutic potential in age-related fibrotic diseases.<br /> (© 2026. The Author(s), under exclusive licence to Springer Nature B.V.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declarations. Competing Interests: The authors declare no competing interests. Ethical approval: The study protocol was approved by the Ethics Committee of Jingzhou Hospital Affiliated to Yangtze University. All animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of the university.
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Ahn SM et al (2016) Emodin from polygonum multiflorum ameliorates oxidative toxicity in HT22 cells and deficits in photothrombotic ischemia. J Ethnopharmacol 188:13–20. https://doi.org/10.1016/j.jep.2016.04.058. (PMID: <searchLink fieldCode="PM" term="%2210%2E1016%2Fj%2Ejep%2E2016%2E04%2E05827151150%22">10.1016/j.jep.2016.04.05827151150)</searchLink><br />Algieri C et al (2025) Mitochondrial dysfunction acts as a modulator of the immunometabolic route for activating the cytosolic DNA sensor pathway in triggering innate immunosurveillance. J Transl Med 23(1):1321. https://doi.org/10.1186/s12967-025-07392-4. (PMID: <searchLink fieldCode="PM" term="%2210%2E1186%2Fs12967-025-07392-44125782812628636%22">10.1186/s12967-025-07392-44125782812628636)</searchLink><br />Alipour-Khezri E et al (2025) Cytosolic DNA sensing pathway in senescence and aging: underlying mechanisms and targeted interventions. Biomed Pharmacother 193:118790. https://doi.org/10.1016/j.biopha.2025.118790. 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              Text: 2026 Jul 06
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              Y: 2026
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