{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:19:22Z","timestamp":1792783162880,"version":"4.5.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Puyang Medical College Research Launch Fund","award":["2024-GW-01"],"award-info":[{"award-number":["2024-GW-01"]}],"id":[{"id":"https:\/\/ror.org\/02qz70527","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biol Rep"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s11033-026-12790-y","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:32:25Z","timestamp":1790573545000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Shikonin attenuates doxorubicin-induced myocardial senescence and fibrosis in association with improved redox and mitochondrial homeostasis"],"prefix":"10.1007","volume":"53","author":[{"given":"Guang-qiu","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-ling","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-qi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan-xia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"12790_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111708","volume":"139","author":"PS Rawat","year":"2021","unstructured":"Rawat PS, Jaiswal A, Khurana A et al (2021) Doxorubicin-induced cardiotoxicity: an update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed Pharmacother 139:111708. https:\/\/doi.org\/10.1016\/j.biopha.2021.111708","journal-title":"Biomed Pharmacother"},{"key":"12790_CR2","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1002\/jcb.29840","volume":"122","author":"S Upadhyay","year":"2021","unstructured":"Upadhyay S, Gupta KB, Mantha AK et al (2021) A short review: doxorubicin and its effect on cardiac proteins. J Cell Biochem 122:153\u2013165. https:\/\/doi.org\/10.1002\/jcb.29840","journal-title":"J Cell Biochem"},{"key":"12790_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114691","volume":"162","author":"S Zhang","year":"2023","unstructured":"Zhang S, Wei X, Zhang H et al (2023) Doxorubicin downregulates autophagy to promote apoptosis-induced dilated cardiomyopathy via regulating the AMPK\/mTOR pathway. Biomed Pharmacother 162:114691. https:\/\/doi.org\/10.1016\/j.biopha.2023.114691","journal-title":"Biomed Pharmacother"},{"key":"12790_CR4","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1007\/s11897-021-00519-w","volume":"18","author":"M Russo","year":"2021","unstructured":"Russo M, Bono E, Ghigo A (2021) The interplay between autophagy and senescence in anthracycline cardiotoxicity. Curr Heart Fail Rep 18:180\u2013190. https:\/\/doi.org\/10.1007\/s11897-021-00519-w","journal-title":"Curr Heart Fail Rep"},{"key":"12790_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119607","volume":"277","author":"CW Kim","year":"2021","unstructured":"Kim CW, Choi KC (2021) Effects of anticancer drugs on the cardiac mitochondrial toxicity and their underlying mechanisms for novel cardiac protective strategies. Life Sci 277:119607. https:\/\/doi.org\/10.1016\/j.lfs.2021.119607","journal-title":"Life Sci"},{"key":"12790_CR6","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.cellsig.2012.01.008","volume":"24","author":"PD Ray","year":"2012","unstructured":"Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981\u2013990. https:\/\/doi.org\/10.1016\/j.cellsig.2012.01.008","journal-title":"Cell Signal"},{"key":"12790_CR7","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01531","volume":"10","author":"H He","year":"2020","unstructured":"He H, Wang L, Qiao Y et al (2020) Doxorubicin induces endotheliotoxicity and mitochondrial dysfunction via ROS\/eNOS\/NO pathway. Front Pharmacol 10:1531. https:\/\/doi.org\/10.3389\/fphar.2019.01531","journal-title":"Front Pharmacol"},{"key":"12790_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.tiv.2018.05.001","volume":"51","author":"J Yin","year":"2018","unstructured":"Yin J, Guo J, Zhang Q et al (2018) Doxorubicin-induced mitophagy and mitochondrial damage is associated with dysregulation of the PINK1\/parkin pathway. Toxicol In Vitro 51:1\u201310. https:\/\/doi.org\/10.1016\/j.tiv.2018.05.001","journal-title":"Toxicol In Vitro"},{"key":"12790_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049639","volume":"7","author":"C Sauvanet","year":"2012","unstructured":"Sauvanet C, Duvezin-Caubet S, Salin B et al (2012) Mitochondrial DNA mutations provoke dominant inhibition of mitochondrial inner membrane fusion. PLoS ONE 7:e49639. https:\/\/doi.org\/10.1371\/journal.pone.0049639","journal-title":"PLoS ONE"},{"key":"12790_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2021.115577","volume":"423","author":"A Gunaydin Akyildiz","year":"2021","unstructured":"Gunaydin Akyildiz A, Boran T, Jannuzzi AT et al (2021) Mitochondrial dynamics imbalance and mitochondrial dysfunction contribute to the molecular cardiotoxic effects of lenvatinib. Toxicol Appl Pharmacol 423:115577. https:\/\/doi.org\/10.1016\/j.taap.2021.115577","journal-title":"Toxicol Appl Pharmacol"},{"key":"12790_CR11","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/s41586-021-03510-6","volume":"593","author":"T Kleele","year":"2021","unstructured":"Kleele T, Rey T, Winter J et al (2021) Distinct fission signatures predict mitochondrial degradation or biogenesis. Nature 593:435\u2013439. https:\/\/doi.org\/10.1038\/s41586-021-03510-6","journal-title":"Nature"},{"key":"12790_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41514-021-00066-7","volume":"7","author":"Y Lyu","year":"2021","unstructured":"Lyu Y, Verma VK, Lee Y et al (2021) Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart. NPJ Aging Mech Dis 7:16. https:\/\/doi.org\/10.1038\/s41514-021-00066-7","journal-title":"NPJ Aging Mech Dis"},{"key":"12790_CR13","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2174\/1566524021666210218112616","volume":"22","author":"A Zia","year":"2022","unstructured":"Zia A, Farkhondeh T, Pourbagher-Shahri AM et al (2022) The roles of mitochondrial dysfunction and reactive oxygen species in aging and senescence. Curr Mol Med 22:37\u201349. https:\/\/doi.org\/10.2174\/1566524021666210218112616","journal-title":"Curr Mol Med"},{"key":"12790_CR14","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.593633","volume":"11","author":"E Yue","year":"2021","unstructured":"Yue E, Yu Y, Wang X et al (2021) Anthocyanin protects cardiac function and cardiac fibroblasts from high-glucose induced inflammation and myocardial fibrosis by inhibiting IL-17. Front Pharmacol 11:593633. https:\/\/doi.org\/10.3389\/fphar.2020.593633","journal-title":"Front Pharmacol"},{"key":"12790_CR15","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1097\/HJH.0000000000000184","volume":"32","author":"H Akahori","year":"2014","unstructured":"Akahori H, Tsujino T, Naito Y et al (2014) Atorvastatin ameliorates cardiac fibrosis and improves left ventricular diastolic function in hypertensive diastolic heart failure model rats. J Hypertens 32:1534\u20131541. https:\/\/doi.org\/10.1097\/HJH.0000000000000184","journal-title":"J Hypertens"},{"key":"12790_CR16","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.3892\/etm.2021.10552","volume":"22","author":"Y Zhong","year":"2021","unstructured":"Zhong Y, Qi A, Liu L et al (2021) Shikonin attenuates H2O2-induced oxidative injury in HT29 cells via antioxidant activities and the inhibition of mitochondrial pathway-mediated apoptosis. Exp Ther Med 22:1118. https:\/\/doi.org\/10.3892\/etm.2021.10552","journal-title":"Exp Ther Med"},{"key":"12790_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153460","volume":"82","author":"Y Chen","year":"2021","unstructured":"Chen Y, Si L, Zhang J et al (2021) Uncovering the antitumor effects and mechanisms of shikonin against colon cancer on comprehensive analysis. Phytomedicine 82:153460. https:\/\/doi.org\/10.1016\/j.phymed.2021.153460","journal-title":"Phytomedicine"},{"key":"12790_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153805","volume":"94","author":"Q Sun","year":"2022","unstructured":"Sun Q, Gong T, Liu M et al (2022) Shikonin, a naphthalene ingredient: therapeutic actions, pharmacokinetics, toxicology, clinical trials and pharmaceutical researches. Phytomedicine 94:153805. https:\/\/doi.org\/10.1016\/j.phymed.2021.153805","journal-title":"Phytomedicine"},{"key":"12790_CR19","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.829642","volume":"15","author":"H Du","year":"2022","unstructured":"Du H, Zhou X, Shi L et al (2022) Shikonin attenuates cochlear spiral ganglion neuron degeneration by activating Nrf2-ARE signaling pathway. Front Mol Neurosci 15:829642. https:\/\/doi.org\/10.3389\/fnmol.2022.829642","journal-title":"Front Mol Neurosci"},{"key":"12790_CR20","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s11033-026-11626-z","volume":"53","author":"GQ Ren","year":"2026","unstructured":"Ren GQ, Liu HJ, Guo YQ et al (2026) Shikonin alleviates high-fat diet-induced vascular aging and dysfunction by inhibiting oxidative stress and mitochondrial damage. Mol Biol Rep 53:461. https:\/\/doi.org\/10.1007\/s11033-026-11626-z","journal-title":"Mol Biol Rep"},{"key":"12790_CR21","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s12012-020-09626-x","volume":"21","author":"L He","year":"2021","unstructured":"He L, Liu F, Li J (2021) Mitochondrial sirtuins and doxorubicin-induced cardiotoxicity. Cardiovasc Toxicol 21:179\u2013191. https:\/\/doi.org\/10.1007\/s12012-020-09626-x","journal-title":"Cardiovasc Toxicol"},{"key":"12790_CR22","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22716","volume":"35","author":"KM Sadek","year":"2021","unstructured":"Sadek KM, Mahmoud SFE, Zeweil MF et al (2021) Proanthocyanidin alleviates doxorubicin-induced cardiac injury by inhibiting NF-\u03baB pathway and modulating oxidative stress, cell cycle, and fibrogenesis. J Biochem Mol Toxicol 35:e22716. https:\/\/doi.org\/10.1002\/jbt.22716","journal-title":"J Biochem Mol Toxicol"},{"key":"12790_CR23","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.toxlet.2019.02.013","volume":"307","author":"M Songbo","year":"2019","unstructured":"Songbo M, Lang H, Xinyong C et al (2019) Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicol Lett 307:41\u201348. https:\/\/doi.org\/10.1016\/j.toxlet.2019.02.013","journal-title":"Toxicol Lett"},{"key":"12790_CR24","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14367","volume":"24","author":"TB Monroe","year":"2025","unstructured":"Monroe TB, Hertzel AV, Dickey DM et al (2025) Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells. Aging Cell 24:e14367. https:\/\/doi.org\/10.1111\/acel.14367","journal-title":"Aging Cell"},{"key":"12790_CR25","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1016\/j.hrthm.2016.05.002","volume":"13","author":"LC Joseph","year":"2016","unstructured":"Joseph LC, Subramanyam P, Radlicz C et al (2016) Mitochondrial oxidative stress during cardiac lipid overload causes intracellular calcium leak and arrhythmia. Heart Rhythm 13:1699\u20131706. https:\/\/doi.org\/10.1016\/j.hrthm.2016.05.002","journal-title":"Heart Rhythm"},{"key":"12790_CR26","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/labinvest.2010.156","volume":"91","author":"Y Liang","year":"2011","unstructured":"Liang Y, Liu D, Ochs T et al (2011) Endogenous sulfur dioxide protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats. Lab Invest 91:12\u201323. https:\/\/doi.org\/10.1038\/labinvest.2010.156","journal-title":"Lab Invest"},{"key":"12790_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.110028","volume":"365","author":"N Ahmad","year":"2022","unstructured":"Ahmad N, Ullah A, Chu P et al (2022) Doxorubicin induced cardiotoxicity through sirtuins-mediated mitochondrial disruption. Chem Biol Interact 365:110028. https:\/\/doi.org\/10.1016\/j.cbi.2022.110028","journal-title":"Chem Biol Interact"},{"key":"12790_CR28","doi-asserted-by":"publisher","first-page":"307","DOI":"10.2147\/JEP.S413256","volume":"15","author":"CG Patintingan","year":"2023","unstructured":"Patintingan CG, Louisa M, Juniantito V et al (2023) Moringa oleifera leaves extract ameliorates doxorubicin-induced cardiotoxicity via its mitochondrial biogenesis modulatory activity in rats. J Exp Pharmacol 15:307\u2013319. https:\/\/doi.org\/10.2147\/JEP.S413256","journal-title":"J Exp Pharmacol"},{"key":"12790_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.113853","volume":"271","author":"W Li","year":"2021","unstructured":"Li W, Ji L, Tian J et al (2021) Ophiopogonin D alleviates diabetic myocardial injuries by regulating mitochondrial dynamics. J Ethnopharmacol 271:113853. https:\/\/doi.org\/10.1016\/j.jep.2021.113853","journal-title":"J Ethnopharmacol"},{"key":"12790_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.199","volume":"4","author":"RM Laberge","year":"2013","unstructured":"Laberge RM, Adler D, Demaria M et al (2013) Mitochondrial DNA damage induces apoptosis in senescent cells. Cell Death Dis 4:e727. https:\/\/doi.org\/10.1038\/cddis.2013.199","journal-title":"Cell Death Dis"},{"key":"12790_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6067","volume":"5","author":"C Mlynarczyk","year":"2014","unstructured":"Mlynarczyk C, F\u00e5hraeus R (2014) Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of p21(CDKN1A). Nat Commun 5:5067. https:\/\/doi.org\/10.1038\/ncomms6067","journal-title":"Nat Commun"},{"key":"12790_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2025.106488","volume":"141","author":"H Sutanto","year":"2025","unstructured":"Sutanto H, Fetarayani D, Narendra MR et al (2025) The role of the senescence-associated secretory phenotype in cardiovascular disease among the elderly. Eur J Intern Med 141:106488. https:\/\/doi.org\/10.1016\/j.ejim.2025.106488","journal-title":"Eur J Intern Med"},{"key":"12790_CR33","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1002\/path.2839","volume":"223","author":"GN Pitiyage","year":"2011","unstructured":"Pitiyage GN, Slijepcevic P, Gabrani A et al (2011) Senescent mesenchymal cells accumulate in human fibrosis by a telomere-independent mechanism and ameliorate fibrosis through matrix metalloproteinases. J Pathol 223:604\u2013617. https:\/\/doi.org\/10.1002\/path.2839","journal-title":"J Pathol"},{"key":"12790_CR34","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1177\/1535370218761628","volume":"243","author":"N Cho","year":"2018","unstructured":"Cho N, Razipour SE, McCain ML (2018) TGF-\u03b21 dominates extracellular matrix rigidity for inducing differentiation of human cardiac fibroblasts to myofibroblasts. Exp Biol Med (Maywood) 243:601\u2013612. https:\/\/doi.org\/10.1177\/1535370218761628","journal-title":"Exp Biol Med (Maywood)"},{"key":"12790_CR35","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1172\/JCI87491","volume":"127","author":"NG Frangogiannis","year":"2017","unstructured":"Frangogiannis NG (2017) The extracellular matrix in myocardial injury, repair, and remodeling. J Clin Invest 127:1600\u20131612. https:\/\/doi.org\/10.1172\/JCI87491","journal-title":"J Clin Invest"},{"key":"12790_CR36","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s13239-020-00514-7","volume":"12","author":"B Roman","year":"2021","unstructured":"Roman B, Kumar SA, Allen SC et al (2021) A model for studying the biomechanical effects of varying ratios of collagen types I and III on cardiomyocytes. Cardiovasc Eng Technol 12:311\u2013324. https:\/\/doi.org\/10.1007\/s13239-020-00514-7","journal-title":"Cardiovasc Eng Technol"},{"key":"12790_CR37","doi-asserted-by":"publisher","first-page":"19723","DOI":"10.1074\/jbc.RA119.009744","volume":"294","author":"V Harikrishnan","year":"2019","unstructured":"Harikrishnan V, Titus AS, Cowling RT et al (2019) Collagen receptor cross-talk determines \u03b1-smooth muscle actin-dependent collagen gene expression in angiotensin II-stimulated cardiac fibroblasts. J Biol Chem 294:19723\u201319739. https:\/\/doi.org\/10.1074\/jbc.RA119.009744","journal-title":"J Biol Chem"}],"container-title":["Molecular Biology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-026-12790-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11033-026-12790-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-026-12790-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:04:13Z","timestamp":1790633053000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11033-026-12790-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["12790"],"URL":"https:\/\/doi.org\/10.1007\/s11033-026-12790-y","relation":{},"ISSN":["0301-4851","1573-4978"],"issn-type":[{"value":"0301-4851","type":"print"},{"value":"1573-4978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]},"assertion":[{"value":"14 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors approved its publication.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"1649"}}