{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:03:28Z","timestamp":1779793408528,"version":"3.53.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":145,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860346"],"award-info":[{"award-number":["81860346"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012253","name":"Guangxi University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012253","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advances in Pharmacological and Pharmaceutical Sciences"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Myocardial infarction (MI) involves a pathological process in which its association with ferroptosis is notably pronounced, and targeted regulation of ferroptosis presents a promising approach for treating MI. This work delineates the molecular basis by which the natural sesquiterpene germacrone protects against cardiomyocyte ferroptosis following isoproterenol (ISO)\u2010induced MI. We established a murine model of ISO\u2010induced MI, paired with an injured H9c2 cardiomyocyte model in vitro. Mice in the experimental group received daily oral germacrone (25, 50, and 100\u2009mg\/kg) for 7 consecutive days. We profiled myocardial injury markers and key nuclear factor erythroid 2\u2013related factor 2 (Nrf2)\/glutathione peroxidase 4 (GPX4) axis proteins. The mechanism of action was confirmed by utilizing ML385, the Nrf2\u2010specific inhibitor. Germacrone significantly reduced ISO\u2010induced myocardial injury in mice, improving cardiac function and decreasing myocardial histopathological damage. Germacrone universally attenuated the elevation of myocardial injury and inflammatory markers in all experimental models. It also decreased the apoptosis rate of H9c2 cells. Germacrone inhibited myocardial ferroptosis and upregulated the abundance of pivotal regulatory proteins, including Nrf2, GPX4, and heme oxygenase\u20101 (HO\u20101), along with solute carrier family 7 member 11 (SLC7A11). ML385, an Nrf2 antagonist, can block germacrone\u2019s protective effect against ISO\u2010induced myocardial ferroptosis and reverse its upregulation of these pathway proteins. These findings provide a new potential target and experimental foundation for MI treatment.<\/jats:p>","DOI":"10.1155\/adpp\/7893262","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T10:17:28Z","timestamp":1779790648000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nrf2\/GPX4\u2010Dependent Ferroptosis Inhibition: The Central Mechanism Underpinning Germacrone\u2010Induced Cardioprotection in Myocardial Infarction"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0780-9320","authenticated-orcid":false,"given":"Jiaxiang","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8584-063X","authenticated-orcid":false,"given":"Zitian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9553-6386","authenticated-orcid":false,"given":"Zhou","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0476-8428","authenticated-orcid":false,"given":"Jincheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8538-2578","authenticated-orcid":false,"given":"Jie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8452-2345","authenticated-orcid":false,"given":"Chunyun","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1587-6825","authenticated-orcid":false,"given":"Dongling","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9851-6029","authenticated-orcid":false,"given":"Fan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8811-6385","authenticated-orcid":false,"given":"Xueling","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7828-8898","authenticated-orcid":false,"given":"Yiling","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3941-4860","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.11.010"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.114.008898"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2024.1423836"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.0358"},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.116.015609"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116457"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1821022116"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2016.10.003"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11070923"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.115270"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.2174\/0118715206312324240805075050"},{"key":"e_1_2_14_12_2","article-title":"Advancements in the Therapeutic Potential of Sesquiterpenoids for the Treatment of Hepatocellular Carcinoma","volume":"67","author":"Li Y.","year":"2025","journal-title":"International Journal of Oncology"},{"key":"e_1_2_14_13_2","first-page":"8","article-title":"The Effects of Germacrone on Lipopolysaccharide-Induced Acute Lung Injury in Neonatal Rats","volume":"60","author":"An J. F.","year":"2014","journal-title":"Cellular and Molecular Biology"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-020-03175-0"},{"key":"e_1_2_14_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2023.2277143"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110876"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11607"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7964"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.199"},{"key":"e_1_2_14_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2957"},{"key":"e_1_2_14_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113562"},{"key":"e_1_2_14_22_2","doi-asserted-by":"publisher","DOI":"10.19540\/j.cnki.cjcmm.20170731.006"},{"key":"e_1_2_14_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/02648725.2023.2197312"},{"key":"e_1_2_14_24_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2021.0063"},{"key":"e_1_2_14_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht367"},{"key":"e_1_2_14_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/hco.0000000000001176"},{"key":"e_1_2_14_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0847-y"},{"key":"e_1_2_14_28_2","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2022-0451"},{"key":"e_1_2_14_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.01.018"},{"key":"e_1_2_14_30_2","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.jcrt_862_16"},{"key":"e_1_2_14_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2022.113595"},{"key":"e_1_2_14_32_2","doi-asserted-by":"publisher","DOI":"10.1159\/000163767"},{"key":"e_1_2_14_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2024.115960"},{"key":"e_1_2_14_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118214"},{"key":"e_1_2_14_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-022-00990-5"},{"key":"e_1_2_14_36_2","first-page":"165","article-title":"Determination of Germacrone in Rat Plasma by HPLC","volume":"13","author":"He H.","year":"2004","journal-title":"Journal of Chinese Pharmaceutical Sciences"},{"key":"e_1_2_14_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.1c00197"},{"key":"e_1_2_14_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac223"},{"key":"e_1_2_14_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu15030591"},{"key":"e_1_2_14_40_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/260429"}],"container-title":["Advances in Pharmacological and Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/adpp\/7893262","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/adpp\/7893262","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/adpp\/7893262","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T10:17:31Z","timestamp":1779790651000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/adpp\/7893262"}},"subtitle":[],"editor":[{"given":"Anjali","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/adpp\/7893262"],"URL":"https:\/\/doi.org\/10.1155\/adpp\/7893262","archive":["Portico"],"relation":{},"ISSN":["2633-4682","2633-4690"],"issn-type":[{"value":"2633-4682","type":"print"},{"value":"2633-4690","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-11-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"7893262"}}