{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:00:45Z","timestamp":1775624445059,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cardiomyocyte senescence contributes to the progression of multiple cardiac diseases, with oxidative stress identified as a central pathophysiological mechanism. Previous animal experiments demonstrated that citronellal (CT), administered at 200\u2009mg\/kg in rats, exerted significant cardioprotective effects. However, the molecular mechanisms underlying these effects remain unclear. This study aimed to investigate the role of CT in mitigating myocardial senescence and to elucidate its mechanistic pathways. Doxorubicin\u2010induced myocardial senescence mouse models and H9C2 cardiomyocyte senescence models were established. SA\u2010\u03b2\u2010gal staining, Western blotting, immunofluorescence, and immunohistochemistry were employed to evaluate senescence and oxidative stress markers. Network pharmacology analysis and molecular docking were conducted to predict CT targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify potential mechanisms of action. CT treatment significantly reduced myocardial oxidative stress levels, ameliorated senescent phenotypes in both in\u00a0vivo and in\u00a0vitro models, and enhanced mitophagy by activating the AMPK\u03b1\u2010mediated PINK1\/Parkin pathway. Bioinformatics analyses further supported the involvement of oxidative stress resistance and mitophagy regulation as central mechanisms underlying CT's cardioprotective effects. Citronellal effectively alleviates cardiomyocyte senescence by reducing oxidative stress and promoting mitophagy through activation of the AMPK\u03b1\u2013PINK1\/Parkin signaling pathway. These findings provide experimental evidence supporting CT as a promising cardioprotective agent and highlight a novel mechanism of action that may inform future therapeutic strategies for cardiac aging and related diseases.<\/jats:p>","DOI":"10.1002\/ptr.70241","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T02:24:54Z","timestamp":1769999094000},"page":"1775-1792","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Citronellal Alleviates Myocardial Senescence by Enhancing Mitochondrial Autophagy via AMPK\u03b1\u2013PINK1\/Parkin Pathway"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2953-2945","authenticated-orcid":false,"given":"Yi\u2010wen","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Pharmacy College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology  Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology  Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao\u2010miao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology  Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian\u2010qian","family":"Niu","sequence":"additional","affiliation":[{"name":"Sino\u2010UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention School of Basic Medical Sciences, College of Pharmacy, Xinxiang Medical University  Xinxiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia\u2010xin","family":"Fan","sequence":"additional","affiliation":[{"name":"Sino\u2010UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention School of Basic Medical Sciences, College of Pharmacy, Xinxiang Medical University  Xinxiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi\u2010ying","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Pharmacy College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology  Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2030-1807","authenticated-orcid":false,"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Sino\u2010UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention School of Basic Medical Sciences, College of Pharmacy, Xinxiang Medical University  Xinxiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3043-6676","authenticated-orcid":false,"given":"Ling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology  Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142702"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp\u20102023\u20100432"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051772"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020\u2010024\u201000817\u20108"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.116"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28124640"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2001"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1196371"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010022\u201000988\u2010z"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12222605"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2024086"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95148"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3308"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2016.1250887"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010016\u20102407\u20107"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2019.0901"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.621509"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202407222"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27660"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1413853"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.02.047"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2020.151108"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976\u20100105.177703"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2016"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11020336"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00774"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmab138"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122382"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202401973"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn3100"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.307474"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015583"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology11071041"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64098"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.197"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.06.053"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.312317"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.11.041"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001378\u20108"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11112241"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1219855"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427\u2010021\u20101982\u20108"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70241","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.70241","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T04:21:14Z","timestamp":1775622074000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,1]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/ptr.70241"],"URL":"https:\/\/doi.org\/10.1002\/ptr.70241","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,1]]},"assertion":[{"value":"2025-05-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}