{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T23:28:47Z","timestamp":1786663727174,"version":"build-2736575974"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":72,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-50719-4","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:14:15Z","timestamp":1780503255000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Suppressive effect of chrysin on macrophage LC3B autophagy through miR-204-5p in diabetic atherosclerosis"],"prefix":"10.1038","volume":"16","author":[{"given":"Chiu-Mei","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Jen","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Ming","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kou-Gi","family":"Shyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"50719_CR1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.tem.2022.11.004","volume":"34","author":"CG Schalkwijk","year":"2023","unstructured":"Schalkwijk, C. G., Micali, L. R. & Wouters, K. Advanced glycation endproducts in diabetes-related macrovascular complications: focus on methylglyoxal. Trends Endocrinol. Metab. 34, 49\u201360 (2023).","journal-title":"Trends Endocrinol. Metab."},{"key":"50719_CR2","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1177\/15353702211038894","volume":"246","author":"D Ni","year":"2021","unstructured":"Ni, D., Mo, Z. & Yi, G. Recent insights into atherosclerotic plaque cell autophagy. Exp. Biol. Med. (Maywood). 246, 2553\u20132558 (2021).","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"50719_CR3","doi-asserted-by":"publisher","first-page":"e13525","DOI":"10.1111\/cpr.13525","volume":"57","author":"W Pan","year":"2024","unstructured":"Pan, W. et al. Comprehensive view of macrophage autophagy and its application in cardiovascular diseases. Cell. Prolif. 57, e13525 (2024).","journal-title":"Cell. Prolif."},{"key":"50719_CR4","doi-asserted-by":"publisher","first-page":"641852","DOI":"10.3389\/fcell.2021.641852","volume":"9","author":"J Xu","year":"2021","unstructured":"Xu, J., Kitada, M., Ogura, Y. & Koya, D. Relationship between autophagy and metabolic syndrome characteristics in the pathogenesis of atherosclerosis. Front. Cell. Dev. Biol. 9, 641852 (2021).","journal-title":"Front. Cell. Dev. Biol."},{"key":"50719_CR5","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1161\/ATVBAHA.123.319993","volume":"44","author":"Z Tian","year":"2024","unstructured":"Tian, Z. et al. Endothelial autophagy promotes atheroprotective communication between endothelial and smooth muscle cells via exosome-mediated delivery of miR-204-5p.  Arterioscler. Thromb. Vasc Biol. 44, 1813\u20131832 (2024).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"50719_CR6","doi-asserted-by":"publisher","first-page":"621324","DOI":"10.3389\/fmolb.2020.621324","volume":"7","author":"YR Qi","year":"2021","unstructured":"Qi, Y. R., Zhao, D. R., Zhao, L., Luo, F. & Yang, M. MiR-520a-3p inhibited macrophage polarization and promoted the development of atherosclerosis via targeting UVRAG in apolipoprotein E knockout mice. Front. Mol. Biosci. 7, 621324 (2021).","journal-title":"Front. Mol. Biosci."},{"key":"50719_CR7","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1161\/HYPERTENSIONAHA.121.14536","volume":"78","author":"J Liu","year":"2021","unstructured":"Liu, J., Liu, Y., Wang, F. & Liang, M. MiR-204: molecular regulation and role in cardiovascular and renal diseases. Hypertension 78, 270\u2013281 (2021).","journal-title":"Hypertension"},{"key":"50719_CR8","doi-asserted-by":"publisher","first-page":"75","DOI":"10.2147\/DMSO.S441082","volume":"17","author":"JJ Dong","year":"2024","unstructured":"Dong, J. J. et al. MicroRNA-2-4-5p ameliorates renal injury via regulating Keap1\/Nrf2 pathway in diabetic kidney diseases. Diabetes Metab. Syndr. Obes. 17, 75\u201392 (2024).","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"50719_CR9","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1038\/s41467-022-29139-1","volume":"13","author":"HJ Hwang","year":"2022","unstructured":"Hwang, H. J. et al. LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy. Nat. Commun. 13, 1436 (2022).","journal-title":"Nat. Commun."},{"key":"50719_CR10","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.intimp.2019.02.054","volume":"70","author":"W Chen","year":"2019","unstructured":"Chen, W. et al. Tanshinone IIA harmonizes the crosstalk of autophagy and polarization in macrophages via miR-375\/KLF4 pathway to attenuate atherosclerosis. Int. Immunopharmcol. 70, 486\u2013497 (2019).","journal-title":"Int. Immunopharmcol"},{"key":"50719_CR11","doi-asserted-by":"publisher","first-page":"2617","DOI":"10.2147\/JIR.S362368","volume":"15","author":"Q Wang","year":"2022","unstructured":"Wang, Q. et al. Inhibition of miRNA-1-mediated inflammation and autophagy by Astragaloside IV improves lipopolysaccharide-Induced cardiac dysfunction in rats. J. Inflamm. Res. 15, 2617\u20132629 (2022).","journal-title":"J. Inflamm. Res."},{"key":"50719_CR12","doi-asserted-by":"publisher","first-page":"17144","DOI":"10.1002\/jcp.28488","volume":"23","author":"T Farkhondeh","year":"2019","unstructured":"Farkhondeh, T., Samarghandian, S. & Roshanavan, B. Impact of chrysin on the molecular mechanisms underlying diabetic complications. J. Cell. Physiol. 23, 17144\u201317158 (2019).","journal-title":"J. Cell. Physiol."},{"key":"50719_CR13","doi-asserted-by":"publisher","first-page":"4345","DOI":"10.1007\/s00394-021-02593-1","volume":"60","author":"CM Lin","year":"2021","unstructured":"Lin, C. M. et al. Chrysin boosts KLF2 expression through suppression of endothelial cell-derived exosomal microRNA-92a in the model of atheroprotection. Eur. J. Nutr. 60, 4345\u20134355 (2021).","journal-title":"Eur. J. Nutr."},{"key":"50719_CR14","doi-asserted-by":"publisher","first-page":"172","DOI":"10.3892\/ijmm.2021.5005","volume":"48","author":"Y He","year":"2021","unstructured":"He, Y. et al. Chrysin induces autophagy through the inactivation of the ROS-mediated Akt\/mTOR signaling pathway in endometrial cancer. Int. J. Mol. Med. 48, 172 (2021).","journal-title":"Int. J. Mol. Med."},{"key":"50719_CR15","doi-asserted-by":"publisher","first-page":"2515","DOI":"10.2147\/DDDT.S79885","volume":"9","author":"NA Qinna","year":"2015","unstructured":"Qinna, N. A. & Badwan, A. A. Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats. Drug Des. Devel Ther. 9, 2515\u20132525 (2015).","journal-title":"Drug Des. Devel Ther."},{"key":"50719_CR16","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1097\/JCMA.0000000000001098","volume":"87","author":"KG Shyu","year":"2024","unstructured":"Shyu, K. G., Wang, B. W., Pan, C. M., Fang, W. J. & Lin, C. M. Exosomal MALAT1 from macrophages treated with high levels of glucose upregulates LC3B expression via miR-204-5p downregulation. J. Chin. Med. Assoc. 87, 581\u2013589 (2024).","journal-title":"J. Chin. Med. Assoc."},{"key":"50719_CR17","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1186\/s12967-025-07075-0","volume":"23","author":"L Cao","year":"2025","unstructured":"Cao, L. et al. Macrophage polarization in diabetic vascular complications: mechanistic insights and therapeutic targets. J. Transl. Med. 23, 1050 (2025).","journal-title":"J. Transl. Med."},{"key":"50719_CR18","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.31083\/j.rcm2204142","volume":"22","author":"ZC Wang","year":"2021","unstructured":"Wang, Z. C., Machuki, J. O., Li, M. Z., Li, K. X. & Sun, H. J. A narrative review of plant and herbal medicines for delaying diabetic atherosclerosis: an update and future perspectives. Rev. Cardiovasc. Med. 22, 1361\u20131381 (2021).","journal-title":"Rev. Cardiovasc. Med."},{"key":"50719_CR19","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.2174\/1389557521666211101162449","volume":"22","author":"RM Dewi","year":"2022","unstructured":"Dewi, R. M., Megawati, M. & Antika, L. D. Antidiabetic properties of dietary chrysin: a cellular mechanism review. Mini Rev. Med. Chem. 22, 1450\u20131457 (2022).","journal-title":"Mini Rev. Med. Chem."},{"key":"50719_CR20","first-page":"853","volume":"26","author":"A Khoshandam","year":"2023","unstructured":"Khoshandam, A., Hedayatian, A., Mollazadeh, A., Razavi, B. M. & Hosseinzadeh, H. Propolis and its constituents against cardiovascular risk factors including obesity, hypertension, atherosclerosis, diabetes, and dyslipidemia: a comprehensive review. Iran. J. Basic. Med. Sci. 26, 853\u2013871 (2023).","journal-title":"J. Basic. Med. Sci."},{"key":"50719_CR21","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1080\/01480545.2019.1687510","volume":"44","author":"W Yao","year":"2021","unstructured":"Yao, W. et al. Toxicological evaluation of a flavonoid, chrysin: morphological, behavioral, biochemical and histopathological assessments in rats. Drug Chem. Toxicol. 44, 601\u2013612 (2021).","journal-title":"Drug Chem. Toxicol."},{"key":"50719_CR22","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1093\/jpp\/rgae140","volume":"77","author":"N Rani","year":"2024","unstructured":"Rani, N. & Arya, N. S. Modulation of PPAR-\u03b3\/Nrf2 and AGE\/RAGE signaling contributes to the chrysin cardioprotection against myocardial damage following ischemia\/reperfusion in diabetic rats. J. Pharm. Pharmacol. 77, 794\u2013804 (2024).","journal-title":"J. Pharm. Pharmacol."},{"key":"50719_CR23","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.3390\/nano14121001","volume":"14","author":"P Pitchakarn","year":"2024","unstructured":"Pitchakarn, P. et al. Multi-endpoint toxicological assessment of chrysin loaded oil-in-water emulsion system in different biological models. Nanomaterials (Basel). 14, 1001 (2024).","journal-title":"Nanomaterials (Basel)"},{"key":"50719_CR24","doi-asserted-by":"publisher","first-page":"4384","DOI":"10.3390\/nu14204384","volume":"14","author":"R Wang","year":"2022","unstructured":"Wang, R. et al. Ginger root extract improves GI health in diabetic rats by improving intestinal integrity and mitochondrial function. Nutrients 14, 4384 (2022).","journal-title":"Nutrients"},{"key":"50719_CR25","doi-asserted-by":"publisher","first-page":"8379","DOI":"10.3390\/ijms21218379","volume":"21","author":"PC Chou","year":"2020","unstructured":"Chou, P. C. et al. Supplemental 25-hydroxycholecalciferol alleviates inflammation and cardiac fibrosis in hens. Int. J. Mol. Sci. 21, 8379 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"50719_CR26","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.1111\/febs.17305","volume":"292","author":"A Vitaliti","year":"2025","unstructured":"Vitaliti, A., Reggio, A. & Palmo, A. Macrophage and autophagy: partner in crime. FEBS J. 292, 2957\u20132972 (2025).","journal-title":"FEBS J."},{"key":"50719_CR27","first-page":"697","volume":"40","author":"H Wang","year":"2025","unstructured":"Wang, H., Ding, K., He, J. & Wang, J. Tetrahydropalmatine promotes macrophage autophagy by inhibiting the AMPK\/mTOR pathway to attenuate atherosclerosis. Histol. Histopathol. 40, 697\u2013710 (2025).","journal-title":"Histol. Histopathol"},{"key":"50719_CR28","doi-asserted-by":"publisher","first-page":"117792","DOI":"10.1016\/j.jep.2024.117792","volume":"324","author":"W Wang","year":"2024","unstructured":"Wang, W. et al. Network pharmacology, molecular docking, and in vitro experimental verification of the mechanism of Guanxining in treating diabetic atherosclerosis. J. Ethnopharmacol. 324, 117792 (2024).","journal-title":"J. Ethnopharmacol."},{"key":"50719_CR29","doi-asserted-by":"publisher","first-page":"121","DOI":"10.2478\/acph-2023-0008","volume":"73","author":"M Yan","year":"2023","unstructured":"Yan, M. et al. Sodium butyrate attenuate hyperglycemia-induced inflammatory response and renal injury in diabetic mice. Acta Pharm. 73, 121\u2013132 (2023).","journal-title":"Acta Pharm."},{"key":"50719_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4103\/1735-5362.329921","volume":"17","author":"A Salama","year":"2021","unstructured":"Salama, A., Asaad, G. F. & Shaheen, A. Chrysin ameliorates STZ-induced diabetes in rats: possible impact of modulation of TLR4\/NF-\u03ba\u03b2 pathway. Res. Pharm. Sci. 17, 1\u201311 (2021).","journal-title":"Res. Pharm. Sci."},{"key":"50719_CR31","doi-asserted-by":"publisher","first-page":"e22052","DOI":"10.1016\/j.heliyon.2023.e22052","volume":"9","author":"G Singh","year":"2023","unstructured":"Singh, G. et al. Chrysin restores the cardioprotective effect of ischemic preconditioning in diabetes-challenged rat heart. Heliyon 9, e22052 (2023).","journal-title":"Heliyon"},{"key":"50719_CR32","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/s41401-024-01356-y","volume":"46","author":"TT Xu","year":"2025","unstructured":"Xu, T. T., Deng, Y. Y., Yu, X. Y., Li, M. & Fu, Y. Y. Natural autophagy modulators in non-communicable diseases: from autophagy mechanisms to therapeutic potential. Acta Pharmacol. Sin. 46, 8\u201332 (2025).","journal-title":"Acta Pharmacol. Sin"},{"key":"50719_CR33","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s40659-024-00521-1","volume":"57","author":"MM Abd El-Emam","year":"2024","unstructured":"Abd El-Emam, M. M. et al. Chrysin-loaded PEGylated liposomes protect against alloxan-induced diabetic neuropathy in rats: the interplay between endoplasmic reticulum stress and autophagy. Biol. Res. 57, 45 (2024).","journal-title":"Biol. Res."},{"key":"50719_CR34","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12933-025-02573-3","volume":"24","author":"N Foussard","year":"2025","unstructured":"Foussard, N. et al. ICAM1 blockade improves ischemic muscle reperfusion in diabetic mice. Cardiovasc. Diabetol. 24, 20 (2025).","journal-title":"Cardiovasc. Diabetol."},{"key":"50719_CR35","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1093\/cvr\/cvaa168","volume":"117","author":"S Ouerd","year":"2021","unstructured":"Ouerd, S. et al. Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1. Cardiovasc. Res. 117, 1144\u20131153 (2021).","journal-title":"Cardiovasc. Res."},{"key":"50719_CR36","doi-asserted-by":"publisher","first-page":"9216","DOI":"10.3390\/ijms21239216","volume":"21","author":"A Taberner-Cort\u00e9s","year":"2020","unstructured":"Taberner-Cort\u00e9s, A. et al. Dapagliflozin does not modulate atherosclerosis in mice with insulin resistance. Int J. Mol. Sci. 21, 9216 (2020).","journal-title":"Int J. Mol. Sci"},{"key":"50719_CR37","doi-asserted-by":"publisher","first-page":"1599321","DOI":"10.3389\/fimmu.2025.1599321","volume":"16","author":"R Mittal","year":"2025","unstructured":"Mittal, R., Lemos, J. R. N., Chapagain, P. & Hirani, K. Interplay of hypoxia, immune dysregulation, and metabolic stress in pathophysiology of type 1 diabetes. Front. Immunol. 16, 1599321 (2025).","journal-title":"Front. Immunol."},{"key":"50719_CR38","first-page":"330","volume":"17","author":"R Wang","year":"2020","unstructured":"Wang, R. et al. Serum microRNA-204 levels are associated with long-term cardiovascular disease risk based on the Framingham risk score in patients with type 2 diabetes: results from an observational study. J. Geriatr. Cardiol. 17, 330\u2013337 (2020).","journal-title":"J. Geriatr. Cardiol."},{"key":"50719_CR39","doi-asserted-by":"crossref","unstructured":"Szydelko, J. & Matyjaszek-Matuszek, B. MicroRNAs as biomarkers for coronary artery disease related to type 2 diabetes mellitus - from pathogenesis to potential clinical application. Phytomedicine 24, 616 (2020).","DOI":"10.3390\/ijms24010616"},{"key":"50719_CR40","doi-asserted-by":"publisher","first-page":"154250","DOI":"10.1016\/j.phymed.2022.154250","volume":"104","author":"LK Wu","year":"2022","unstructured":"Wu, L. K. et al. Artemisia leaf extract protects against neuron toxicity by TRPML1 activation and promoting autophagy\/mitophagy clearance in both in vitro and in vivo models of MPP+\/MPTP-induced Parkinson\u2019s disease. Phytomedicine 104, 154250 (2022).","journal-title":"Phytomedicine"},{"key":"50719_CR41","doi-asserted-by":"publisher","first-page":"1130662","DOI":"10.3389\/fimmu.2023.1130662","volume":"14","author":"ESA Sousa","year":"2023","unstructured":"Sousa, E. S. A. et al. The influence of high glucose conditions on macrophages and its effect on the autophagy pathway. Front. Immunol. 14, 1130662 (2023).","journal-title":"Front. Immunol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50719-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50719-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50719-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T23:08:48Z","timestamp":1786662528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50719-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["50719"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-50719-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-8343027\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"assertion":[{"value":"12 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"25372"}}