{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:03:25Z","timestamp":1790373805148,"version":"4.1.0"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873461"],"award-info":[{"award-number":["81873461"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.intimp.2025.114086","type":"journal-article","created":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T00:57:39Z","timestamp":1737248259000},"page":"114086","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["Plumbagin improves myocardial fibrosis after myocardial infarction by inhibiting the AKT\/mTOR pathway to upregulate autophagy levels"],"prefix":"10.1016","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8223-7875","authenticated-orcid":false,"given":"Suxiang","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luzheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kongli","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"8","key":"10.1016\/j.intimp.2025.114086_b0005","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1161\/CIR.0000000000001123","article-title":"Heart disease and stroke statistics-2023 update: a report from the American heart association","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"issue":"6","key":"10.1016\/j.intimp.2025.114086_b0010","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41569-022-00823-5","article-title":"Macrophages in cardiac remodelling after myocardial infarction","volume":"20","author":"Yap","year":"2023","journal-title":"Nat. Rev. Cardiol."},{"issue":"3","key":"10.1016\/j.intimp.2025.114086_b0015","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1161\/CIRCRESAHA.121.319584","article-title":"Multiple cell death programs contribute to myocardial infarction","volume":"129","author":"Jia","year":"2021","journal-title":"Circ. Res."},{"issue":"1","key":"10.1016\/j.intimp.2025.114086_b0020","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","article-title":"The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ Res"},{"key":"10.1016\/j.intimp.2025.114086_b0025","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jconrel.2015.06.036","article-title":"Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction","volume":"213","author":"Yang","year":"2015","journal-title":"J. Control. Release"},{"issue":"6576","key":"10.1016\/j.intimp.2025.114086_b0030","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1126\/science.abm0594","article-title":"CAR T cells produced in vivo to treat cardiac injury","volume":"375","author":"Rurik","year":"2022","journal-title":"Science"},{"issue":"9351","key":"10.1016\/j.intimp.2025.114086_b0035","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0140-6736(03)12113-7","article-title":"Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials","volume":"361","author":"Keeley","year":"2003","journal-title":"Lancet"},{"issue":"6","key":"10.1016\/j.intimp.2025.114086_b0040","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1093\/cvr\/cvz336","article-title":"Cardiac monocytes and macrophages after myocardial infarction","volume":"116","author":"Peet","year":"2020","journal-title":"Cardiovasc. Res."},{"issue":"9","key":"10.1016\/j.intimp.2025.114086_b0045","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart disease and stroke statistics-2020 update: a report from the American heart association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"issue":"10120","key":"10.1016\/j.intimp.2025.114086_b0050","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0140-6736(17)32520-5","article-title":"Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals","volume":"391","author":"Conrad","year":"2018","journal-title":"Lancet"},{"issue":"6","key":"10.1016\/j.intimp.2025.114086_b0055","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1161\/CIRCRESAHA.115.306565","article-title":"Cardiac fibrosis: the fibroblast awakens","volume":"118","author":"Travers","year":"2016","journal-title":"Circ. Res."},{"issue":"11","key":"10.1016\/j.intimp.2025.114086_b0060","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1253\/circj.CJ-16-1003","article-title":"Defining the cardiac fibroblast","volume":"80","author":"Ivey","year":"2016","journal-title":"Circ. J."},{"issue":"5","key":"10.1016\/j.intimp.2025.114086_b0065","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1097\/FJC.0b013e31821823d9","article-title":"Biomarkers of myocardial fibrosis","volume":"57","author":"de Jong","year":"2011","journal-title":"J. Cardiovasc. Pharmacol."},{"issue":"8","key":"10.1016\/j.intimp.2025.114086_b0070","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1161\/CIRCRESAHA.118.314438","article-title":"Protective effects of activated myofibroblasts in the pressure-overloaded myocardium are mediated through smad-dependent activation of a matrix-preserving program","volume":"124","author":"Russo","year":"2019","journal-title":"Circ. Res."},{"issue":"13","key":"10.1016\/j.intimp.2025.114086_b0075","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1056\/NEJMra072139","article-title":"Cardiac plasticity","volume":"358","author":"Hill","year":"2008","journal-title":"N. Engl. J. Med."},{"issue":"3","key":"10.1016\/j.intimp.2025.114086_b0080","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.jacbts.2019.02.006","article-title":"Fibroblasts in the infarcted, remodeling, and failing heart","volume":"4","author":"Humeres","year":"2019","journal-title":"JACC Basic Transl. Sci."},{"issue":"1","key":"10.1016\/j.intimp.2025.114086_b0085","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1111\/j.1755-5922.2010.00228.x","article-title":"Targeting fibrosis for the treatment of heart failure: a role for transforming growth factor-\u03b2","volume":"30","author":"Edgley","year":"2012","journal-title":"Cardiovasc. Ther."},{"key":"10.1016\/j.intimp.2025.114086_b0090","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3389\/fcvm.2019.00140","article-title":"The role of the TGF-\u03b2 superfamily in myocardial infarction","volume":"6","author":"Hanna","year":"2019","journal-title":"Front. Cardiovasc. Med."},{"issue":"10","key":"10.1016\/j.intimp.2025.114086_b0095","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd3810","article-title":"Targeting the TGF\u03b2 signalling pathway in disease","volume":"11","author":"Akhurst","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"issue":"9","key":"10.1016\/j.intimp.2025.114086_b0100","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1021\/np50123a003","article-title":"Natural product drug discovery and development: new perspectives on international collaboration","volume":"58","author":"Baker","year":"1995","journal-title":"J. Nat. Prod."},{"issue":"13","key":"10.1016\/j.intimp.2025.114086_b0105","doi-asserted-by":"crossref","DOI":"10.1111\/jcmm.18386","article-title":"Plumbagin ameliorates LPS-induced acute lung injury by regulating PI3K\/AKT\/mTOR and Keap1-Nrf2\/HO-1 signalling pathways","volume":"28","author":"Liu","year":"2024","journal-title":"J. Cell Mol. Med."},{"key":"10.1016\/j.intimp.2025.114086_b0110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2023.03.263","article-title":"Plumbagin is a novel GPX4 protein degrader that induces apoptosis in hepatocellular carcinoma cells","volume":"203","author":"Yao","year":"2023","journal-title":"Free Radic. Biol. Med."},{"issue":"1","key":"10.1016\/j.intimp.2025.114086_b0115","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13223-022-00734-7","article-title":"Plumbagin attenuates Bleomycin-induced lung fibrosis in mice","volume":"18","author":"Mehdizadeh","year":"2022","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"10.1016\/j.intimp.2025.114086_b0120","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.108923","article-title":"Plumbagin ameliorates liver fibrosis via a ROS-mediated NF-\u043aB signaling pathway in vitro and in vivo","volume":"116","author":"Chen","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.intimp.2025.114086_b0125","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.12659\/MSM.897618","article-title":"Plumbagin Mediates Cardioprotection Against Myocardial Ischemia\/Reperfusion Injury Through Nrf-2 Signaling","volume":"22","author":"Wang","year":"2016","journal-title":"Med. Sci. Monit."},{"issue":"2","key":"10.1016\/j.intimp.2025.114086_b0130","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3892\/etm.2022.11428","article-title":"Plumbagin protects H9c2 cardiomyocytes against TBHP-induced cytotoxicity by alleviating ROS-induced apoptosis and modulating autophagy","volume":"24","author":"Zhang","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.intimp.2025.114086_b0135","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.714390","article-title":"Methyl ferulic acid attenuates human cardiac fibroblasts differentiation and myocardial fibrosis by suppressing pRB-E2F1\/CCNE2 and RhoA\/ROCK2 pathway","volume":"12","author":"Liao","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.intimp.2025.114086_b0140","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev-immunol-101320-031555","article-title":"Functional hallmarks of healthy macrophage responses: their regulatory basis and disease relevance","volume":"40","author":"Sheu","year":"2022","journal-title":"Annu. Rev. Immunol."},{"issue":"5","key":"10.1016\/j.intimp.2025.114086_b0145","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.immuni.2021.04.021","article-title":"Fibroblast-macrophage reciprocal interactions in health, fibrosis, and cancer","volume":"54","author":"Buechler","year":"2021","journal-title":"Immunity"},{"issue":"3","key":"10.1016\/j.intimp.2025.114086_b0150","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.yjmcc.2009.06.012","article-title":"Extracellular matrix turnover and signaling during cardiac remodeling following MI: causes and consequences","volume":"48","author":"Zamilpa","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"issue":"7","key":"10.1016\/j.intimp.2025.114086_b0155","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/s41569-021-00646-w","article-title":"Transforming growth factor-\u03b2 in myocardial disease","volume":"19","author":"Frangogiannis","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"issue":"3","key":"10.1016\/j.intimp.2025.114086_b0160","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1093\/cvr\/cvab110","article-title":"Myocardin-related transcription factor A regulates integrin beta 2 transcription to promote macrophage infiltration and cardiac hypertrophy in mice","volume":"118","author":"Liu","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.intimp.2025.114086_b0165","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.fct.2019.01.018","article-title":"Emerging role of plumbagin: Cytotoxic potential and pharmaceutical relevance towards cancer therapy","volume":"125","author":"Tripathi","year":"2019","journal-title":"Food Chem. Toxicol."},{"issue":"12","key":"10.1016\/j.intimp.2025.114086_b0170","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1158\/1535-7163.MCT-06-0478","article-title":"Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT\/mammalian target of rapamycin pathway in breast cancer cells","volume":"5","author":"Kuo","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.intimp.2025.114086_b0175","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1186\/s12935-020-01607-y","article-title":"Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K\/AKT\/mTOR signaling pathways and EMT","volume":"20","author":"Zhang","year":"2020","journal-title":"Cancer Cell Int."},{"issue":"4","key":"10.1016\/j.intimp.2025.114086_b0180","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: renovation of cells and tissues","volume":"147","author":"Mizushima","year":"2011","journal-title":"Cell"},{"issue":"3","key":"10.1016\/j.intimp.2025.114086_b0185","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4161\/auto.7.3.14487","article-title":"Selective autophagy mediated by autophagic adapter proteins","volume":"7","author":"Johansen","year":"2011","journal-title":"Autophagy"},{"issue":"6","key":"10.1016\/j.intimp.2025.114086_b0190","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.cell.2007.10.035","article-title":"Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice","volume":"131","author":"Komatsu","year":"2007","journal-title":"Cell"},{"issue":"5","key":"10.1016\/j.intimp.2025.114086_b0195","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.jhep.2020.04.044","article-title":"Hepatic stellate cell autophagy inhibits extracellular vesicle release to attenuate liver fibrosis","volume":"73","author":"Gao","year":"2020","journal-title":"J. Hepatol."},{"issue":"8","key":"10.1016\/j.intimp.2025.114086_b0200","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/s41580-023-00585-z","article-title":"Autophagy and autophagy-related pathways in cancer","volume":"24","author":"Debnath","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"1","key":"10.1016\/j.intimp.2025.114086_b0205","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","article-title":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer","volume":"22","author":"Glaviano","year":"2023","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.intimp.2025.114086_b0210","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ijbiomac.2021.02.029","article-title":"SIRT3 ameliorates osteoarthritis via regulating chondrocyte autophagy and apoptosis through the PI3K\/Akt\/mTOR pathway","volume":"175","author":"Xu","year":"2021","journal-title":"Int. J. Biol. Macromol."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S156757692500075X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S156757692500075X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:58:51Z","timestamp":1740617931000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S156757692500075X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":42,"alternative-id":["S156757692500075X"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2025.114086","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Plumbagin improves myocardial fibrosis after myocardial infarction by inhibiting the AKT\/mTOR pathway to upregulate autophagy levels","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2025.114086","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"114086"}}