{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:24:39Z","timestamp":1786944279212,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014857","name":"National Natural Science Foundation of China-Guangdong Joint Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010031","name":"Postdoctoral Research Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010031","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Doxorubicin (Dox)-induced cardiotoxicity (DIC) is initiated by acute stress that triggers early senescence-like phenotypes and severe metabolic maladaptation, yet effective therapeutic interventions remain elusive.\n                      <jats:italic>Tricholoma matsutake<\/jats:italic>\n                      polypeptide (TMP), a bioactive component from a medicinal fungus, exhibits antioxidant properties, but its potential to modulate cardiac energy metabolism remains unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vivo<\/jats:italic>\n                      , Sprague-Dawley rats were administered Dox (20\u00a0mg\/kg, i.p.) with or without TMP (200\/400\u00a0mg\/kg\/day) for 7 days. Cardiac function was assessed via high-resolution echocardiography, and metabolic signatures were decoded using LC-MS\/MS-based untargeted metabolomics.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , H9c2 cardiomyocytes were co-treated with Dox (5\u00a0\u03bcM) and TMP (30\u00a0\u03bcg\/mL). Senescence phenotypes (SA-\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -gal), mitochondrial dynamics (JC-1\/Fura-2AM), and energy metabolites (ATP\/NAD+) were quantified. Mechanistic axes were interrogated via Western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TMP significantly attenuated Dox-induced cardiac dysfunction, interstitial fibrosis, and inflammation. Metabolomics revealed that TMP mitigated the glycolysis-dominant metabolic reprogramming, restored phospholipid homeostasis, and preserved the nucleotide pool. In cardiomyocytes, TMP antagonized premature senescence and suppressed ROS generation without compromising Dox\u2019s antitumor efficacy in MCF-7 cells. Mechanistically, TMP alleviated the Dox-induced blockade of autophagic flux (restoring Beclin1\/p-Parkin) and reactivated the AMPK\/Sirt1\/PGC-1\u03b1 energy-sensing pathway, thereby preserving the ATP\/NAD + reserve.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TMP functions as a metabolic modulator that protects against DIC by reprogramming energy metabolism and restoring mitochondrial quality control. These findings highlight TMP as a promising adjuvant for preserving cardiovascular health in cancer survivors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1842003","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:35:29Z","timestamp":1786941329000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tricholoma matsutake polypeptide modulates cardiac metabolism and restores autophagic flux to mitigate doxorubicin-induced senescence"],"prefix":"10.3389","volume":"17","author":[{"given":"Ting","family":"Ye","sequence":"first","affiliation":[{"name":"Molecular Medicine Innovation Center, Cancer Institute of the Affiliated Hospital of Qingdao University, Qingdao University","place":["Qingdao, China"]},{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-shi","family":"Wang","sequence":"additional","affiliation":[{"name":"Molecular Medicine Innovation Center, Cancer Institute of the Affiliated Hospital of Qingdao University, Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-wen","family":"Ge","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-jiao","family":"Li","sequence":"additional","affiliation":[{"name":"Molecular Medicine Innovation Center, Cancer Institute of the Affiliated Hospital of Qingdao University, Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Molecular Medicine Innovation Center, Cancer Institute of the Affiliated Hospital of Qingdao University, Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-she","family":"Sun","sequence":"additional","affiliation":[{"name":"Molecular Medicine Innovation Center, Cancer Institute of the Affiliated Hospital of Qingdao University, Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-ming","family":"Xing","sequence":"additional","affiliation":[{"name":"Molecular Medicine Innovation Center, Cancer Institute of the Affiliated Hospital of Qingdao University, Qingdao University","place":["Qingdao, China"]},{"name":"School of Life Sciences, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1161\/circulationaha.121.056589","article-title":"NAD(+) metabolism in cardiac health, aging, and disease","volume":"144","author":"Abdellatif","year":"2021","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2025.1591","article-title":"Sex- and age-dependent metabolic and inflammatory pathways in cardiomyopathy: the role of sirtuins, inflammaging and mitochondrial homeostasis","author":"Barcena","year":"2026","journal-title":"Aging Dis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.ejheart.2006.09.007","article-title":"Monitoring left ventricular function in adults receiving anthracycline-containing chemotherapy","volume":"9","author":"Belham","year":"2007","journal-title":"Eur. 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