{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:53:47Z","timestamp":1791910427623,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science, and Technology","doi-asserted-by":"crossref","award":["RS-2023-00208905"],"award-info":[{"award-number":["RS-2023-00208905"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Aging contributes to neurodegeneration, predominantly characterized by increased oxidative stress, which leads to neurodegenerative changes and cognitive decline. This cognitive impairment is often associated with neuroinflammation, oxidative stress, and neuronal damage. Exercise is widely recognized for its capacity to elevate levels of irisin, a hormone derived from the cleavage of fibronectin type III domain-containing protein 5 (FNDC5). FNDC5\/irisin acts as a myokine that mediates numerous beneficial effects of physical activity on metabolic health. It has also been recognized for its neuroprotective roles, suggesting its potential to mitigate neurodegenerative processes by promoting neuronal survival, reducing oxidative stress, and enhancing synaptic plasticity. However, the specific impact of exercise on the FNDC5\/irisin pathway and antioxidant mechanisms in the aged brain remains insufficiently explored. In this study, we aimed to validate the neuroprotective role of exercise-induced FNDC5\/irisin against aging-related oxidative stress, glial activation, neuronal damage, and cognitive impairment in 20-month-old mice. The exercise group underwent treadmill running for 60 min daily over an 8-week period. Our findings indicated that aging mice exhibited cognitive impairment, as evidenced by the Y-maze test; however, treadmill exercise effectively alleviated this impairment. Aged mice showed the activation of microglia and astrocytes in the hippocampus, which was notably reduced by exercise. Moreover, exercise improved the levels of calbindin and irisin, which were diminished due to aging. Our study demonstrated that aging led to a decrease in the antioxidant response element system and FNDC5\/irisin pathway. However, exercise effectively activated Nrf2 and FNDC5\/irisin expression, subsequently enhancing levels of SOD1, GSTO1\/2, Sirt1, PGC-1\u03b1, BDNF, IGF-1, and IGF-2 in the hippocampus. The exercise-induced activation of Nrf2 signaling and FNDC5\/irisin has emerged as a potent mechanism for alleviating oxidative stress and neuroinflammation associated with aging. In conclusion, our findings suggest that regular exercise has the potential to alleviate cognitive impairment through the activation of PGC-1\u03b1-FNDC5\/irisin signaling, the Nrf2 ARE system, and neurotrophic factors in aged mice.<\/jats:p>","DOI":"10.3390\/antiox14101239","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:04:02Z","timestamp":1760537042000},"page":"1239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Exercise-Induced FNDC5\/Irisin Ameliorates Cognitive Impairment in Aged Mice, Associated with Antioxidant and Neurotrophic Responses"],"prefix":"10.3390","volume":"14","author":[{"given":"Jae Min","family":"Lee","sequence":"first","affiliation":[{"name":"College of Nursing Science, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Otorhinolaryngology Head & Neck Surgery, College of Medicine, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hyeok","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Nursing, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Nursing, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3233-1229","authenticated-orcid":false,"given":"You Jung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Nursing, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Nursing Science, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"College of Nursing, Woosuk University, 443 Samnye-ro, Samnye-eup, Wanju_Gun, Wangju 55338, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Geun","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head & Neck Surgery, College of Medicine, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4991-0825","authenticated-orcid":false,"given":"Youn-Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Nursing Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41392-022-01251-0","article-title":"Aging and Aging-Related Diseases: From Molecular Mechanisms to Interventions and Treatments","volume":"7","author":"Guo","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Scisciola, L., Fontanella, R.A., Cataldo, V., Paolisso, G., and Barbieri, M. (2021). Sarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk. Life, 11.","DOI":"10.3390\/life11020173"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1152\/advan.00101.2014","article-title":"Exercise, Cognitive Function, and Aging","volume":"39","author":"Barnes","year":"2015","journal-title":"Adv. Physiol. Educ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1152\/japplphysiol.00500.2006","article-title":"Exercise, Cognition, and the Aging Brain","volume":"101","author":"Kramer","year":"2006","journal-title":"J. Appl. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mee-inta, O., Zhao, Z.-W., and Kuo, Y.-M. (2019). Physical Exercise Inhibits Inflammation and Microglial Activation. Cells, 8.","DOI":"10.3390\/cells8070691"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1152\/japplphysiol.00080.2007","article-title":"Role of Myokines in Exercise and Metabolism","volume":"103","author":"Pedersen","year":"2007","journal-title":"J. Appl. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10522-021-09910-5","article-title":"Aging and Age\u2014related Diseases: From Mechanisms to Therapeutic Strategies","volume":"22","author":"Li","year":"2021","journal-title":"Biogerontology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41591-018-0275-4","article-title":"Exercise-Linked FNDC5\/Irisin Rescues Synaptic Plasticity and Memory Defects in Alzheimer\u2019s Models","volume":"25","author":"Lourenco","year":"2019","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lee, B., Shin, M., Park, Y., Won, S.-Y., and Cho, K.S. (2021). Physical Exercise-Induced Myokines in Neurodegenerative Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115795"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kwon, J.H., Moon, K.M., and Min, K.-W. (2020). Exercise-Induced Myokines Can Explain the Importance of Physical Activity in the Elderly: An Overview. Healthcare, 8.","DOI":"10.3390\/healthcare8040378"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s00125-014-3224-x","article-title":"Myokines in Insulin Resistance and Type 2 Diabetes","volume":"57","author":"Eckardt","year":"2014","journal-title":"Diabetologia"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Laurens, C., Bergouignan, A., and Moro, C. (2020). Exercise-Released Myokines in the Control of Energy Metabolism. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00091"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jo, D., Yoon, G., Kim, O.Y., and Song, J. (2022). A New Paradigm in Sarcopenia: Cognitive Impairment Caused by Imbalanced Myokine Secretion and Vascular Dysfunction. Biomed. Pharmacother., 147.","DOI":"10.1016\/j.biopha.2022.112636"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Waseem, R., Shamsi, A., Mohammad, T., Hassan, M.I., Kazim, S.N., Chaudhary, A.A., Rudayni, H.A., Al-Zharani, M., Ahmad, F., and Islam, A. (2022). FNDC5\/Irisin: Physiology and Pathophysiology. Molecules, 27.","DOI":"10.3390\/molecules27031118"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cmet.2013.09.008","article-title":"Exercise Induces Hippocampal BDNF through a PGC-1\u03b1\/FNDC5 Pathway","volume":"18","author":"Wrann","year":"2013","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Leger, C., Quiri\u00e9, A., M\u00e9loux, A., Fontanier, E., Chaney, R., Basset, C., Lemaire, S., Garnier, P., and Prigent-Tessier, A. (2024). Impact of Exercise Intensity on Cerebral BDNF Levels: Role of FNDC5\/Irisin. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021213"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.mrfmmm.2009.09.007","article-title":"A Protective Role of Nuclear Factor-Erythroid 2-Related Factor-2 (Nrf2) in Inflammatory Disorders","volume":"690","author":"Kim","year":"2010","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of Nrf2 in Oxidative Stress and Toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Saha, S., Buttari, B., Panieri, E., Profumo, E., and Saso, L. (2020). An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation. Molecules, 25.","DOI":"10.3390\/molecules25225474"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.freeradbiomed.2015.07.147","article-title":"Nrf2\u2014A Therapeutic Target for the Treatment of Neurodegenerative Diseases","volume":"88","author":"Johnson","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yang, Y., Liu, Y., Wang, Y., Chao, Y., Zhang, J., Jia, Y., Tie, J., and Hu, D. (2022). Regulation of SIRT1 and Its Roles in Inflammation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.831168"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/MOL.0b013e328328d0a4","article-title":"PGC-1alpha, SIRT1 and AMPK, an Energy Sensing Network That Controls Energy Expenditure","volume":"20","author":"Auwerx","year":"2009","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.5114\/aoms.2015.56342","article-title":"Brain-Derived Neurotrophic Factor and Its Clinical Implications","volume":"11","author":"Bathina","year":"2015","journal-title":"Arch. Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.tem.2013.12.001","article-title":"SIRT1 and Other Sirtuins in Metabolism","volume":"25","author":"Chang","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"He, F., Ru, X., and Wen, T. (2020). NRF2, a Transcription Factor for Stress Response and Beyond. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134777"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, M., Su, S., Cai, W., Cao, J., Miao, X., Zang, W., Gao, S., Xu, Y., Yang, J., and Tao, Y.-X. (2020). Differentially Expressed Genes in the Brain of Aging Mice with Cognitive Alteration and Depression- and Anxiety-Like Behaviors. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00814"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14385","DOI":"10.1073\/pnas.2334169100","article-title":"Spatial Memory Performances of Aged Rats in the Water Maze Predict Levels of Hippocampal Neurogenesis","volume":"100","author":"Drapeau","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kraeuter, A.-K., Guest, P.C., and Sarnyai, Z. (2019). The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Pre-Clinical Models: Techniques and Protocols, Springer.","DOI":"10.1007\/978-1-4939-8994-2_10"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/jnr.490420310","article-title":"Brain Injury and Tumor Necrosis Factors Induce Calbindin D\u201428K in Astrocytes: Evidence for a Cytoprotective Response","volume":"42","author":"Mattson","year":"1995","journal-title":"J. Neurosci. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1038\/cdd.2014.67","article-title":"Crucial Role of Calbindin-D28k in the Pathogenesis of Alzheimer\u2019s Disease Mouse Model","volume":"21","author":"Kook","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.neulet.2012.03.092","article-title":"Hippocampal Calbindin-1 Immunoreactivity Correlate of Recognition Memory Performance in Aged Mice","volume":"516","author":"Soontornniyomkij","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.pcad.2019.02.007","article-title":"A Role for FNDC5\/Irisin in the Beneficial Effects of Exercise on the Brain and in Neurodegenerative Diseases","volume":"62","author":"Young","year":"2019","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chung, W.-S., Allen, N.J., and Eroglu, C. (2015). Astrocytes Control Synapse Formation, Function, and Elimination. Cold Spring Harb. Perspect Biol., 7.","DOI":"10.1101\/cshperspect.a020370"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.pharmthera.2013.04.013","article-title":"Microglia during Development and Aging","volume":"139","author":"Harry","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"von Bernhardi, R., Eugen\u00edn-von Bernhardi, L., and Eugen\u00edn, J. (2015). Microglial Cell Dysregulation in Brain Aging and Neurodegeneration. Front. Aging Neurosci., 7.","DOI":"10.3389\/fnagi.2015.00124"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1210\/endrev\/bnab003","article-title":"Progress and Challenges in the Biology of FNDC5 and Irisin","volume":"42","author":"Maak","year":"2021","journal-title":"Endocr. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/s12017-018-8500-3","article-title":"Exercise Training Protects Against Aging-Induced Cognitive Dysfunction via Activation of the Hippocampal PGC-1\u03b1\/FNDC5\/BDNF Pathway","volume":"20","author":"Okudan","year":"2018","journal-title":"Neuromol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6852","DOI":"10.18632\/aging.103046","article-title":"Swimming Exercise Stimulates IGF1\/PI3K\/Akt and AMPK\/SIRT1\/PGC1\u03b1 Survival Signaling to Suppress Apoptosis and Inflammation in Aging Hippocampus","volume":"12","author":"Lin","year":"2020","journal-title":"Aging"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1523\/JNEUROSCI.2939-14.2015","article-title":"SIRT1 Deficiency in Microglia Contributes to Cognitive Decline in Aging and Neurodegeneration via Epigenetic Regulation of IL-1\u03b2","volume":"35","author":"Cho","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.neuron.2014.01.028","article-title":"SIRT1 in Neurodevelopment and Brain Senescence","volume":"81","author":"Herskovits","year":"2014","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5368","DOI":"10.1523\/JNEUROSCI.6251-09.2010","article-title":"Brain-Derived Neurotrophic Factor Is Associated with Age-Related Decline in Hippocampal Volume","volume":"30","author":"Erickson","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e12989","DOI":"10.1111\/acel.12989","article-title":"Aging\u2014Induced Akt Activation Involves in Aging\u2014Related Pathologies and A\u03b2\u2014Induced Toxicity","volume":"18","author":"Chen","year":"2019","journal-title":"Aging Cell"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ortega-Mart\u00ednez, S. (2015). A New Perspective on the Role of the CREB Family of Transcription Factors in Memory Consolidation via Adult Hippocampal Neurogenesis. Front. Mol. Neurosci., 8.","DOI":"10.3389\/fnmol.2015.00046"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7121827","DOI":"10.1155\/2017\/7121827","article-title":"SIRT1 Regulates Cognitive Performance and Ability of Learning and Memory in Diabetic and Nondiabetic Models","volume":"2017","author":"Cao","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sonntag, W.E., Deak, F., Ashpole, N., Toth, P., Csiszar, A., Freeman, W., and Ungvari, Z. (2013). Insulin-like Growth Factor-1 in CNS and Cerebrovascular Aging. Front. Aging Neurosci., 5.","DOI":"10.3389\/fnagi.2013.00027"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ecl.2012.04.008","article-title":"Insulin-Like Growth Factor 1 Physiology","volume":"41","author":"Yakar","year":"2012","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Labandeira-Garcia, J.L., Costa-Besada, M.A., Labandeira, C.M., Villar-Cheda, B., and Rodr\u00edguez-Perez, A.I. (2017). Insulin-Like Growth Factor-1 and Neuroinflammation. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00365"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kandlur, A., Satyamoorthy, K., and Gangadharan, G. (2020). Oxidative Stress in Cognitive and Epigenetic Aging: A Retrospective Glance. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.00041"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13291","DOI":"10.1074\/jbc.R900010200","article-title":"The Nrf2-Antioxidant Response Element Signaling Pathway and Its Activation by Oxidative Stress","volume":"284","author":"Nguyen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.freeradbiomed.2015.05.036","article-title":"Oxidative Stress Response and Nrf2 Signaling in Aging","volume":"88","author":"Zhang","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0197-0186(00)00063-2","article-title":"Regular Exercise Improves Cognitive Function and Decreases Oxidative Damage in Rat Brain","volume":"38","author":"Kaneko","year":"2001","journal-title":"Neurochem. Int."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Souza, J., da Silva, R.A., da Luz Scheffer, D., Penteado, R., Solano, A., Barros, L., Budde, H., Trostchansky, A., and Latini, A. (2022). Physical-Exercise-Induced Antioxidant Effects on the Brain and Skeletal Muscle. Antioxidants, 11.","DOI":"10.3390\/antiox11050826"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/s41419-024-06748-w","article-title":"FNDC5 Prevents Oxidative Stress and Neuronal Apoptosis after Traumatic Brain Injury through SIRT3-Dependent Regulation of Mitochondrial Quality Control","volume":"15","author":"Ge","year":"2024","journal-title":"Cell Death Dis."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/10\/1239\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T04:41:20Z","timestamp":1760676080000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/10\/1239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":53,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["antiox14101239"],"URL":"https:\/\/doi.org\/10.3390\/antiox14101239","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,15]]}}}