{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:22:43Z","timestamp":1789392163013,"version":"build-2803163510"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004054","name":"King Abdulaziz University","doi-asserted-by":"publisher","award":["IPP:594-166-2025"],"award-info":[{"award-number":["IPP:594-166-2025"]}],"id":[{"id":"10.13039\/501100004054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Doxorubicin (DOX) is an effective anthracycline chemotherapeutic agent, but its clinical use is limited by dose-dependent cardiotoxicity associated with oxidative stress, inflammation, and apoptosis. Biochanin A (BCA), an O-methylated isoflavone, has demonstrated antioxidant and anti-inflammatory properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study investigated whether BCA could mitigate DOX-induced cardiac injury in rats and explored the underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Wistar rats were randomly assigned to control, BCA-alone, DOX-alone, and DOX combined with BCA (25 or 50\u2005mg\/kg) groups. Cardiotoxicity was induced by DOX administration. Electrocardiographic (ECG) parameters were recorded, and serum cardiac biomarkers (CK-MB, LDH, and troponin) were measured. Cardiac tissue was evaluated for oxidative stress markers, antioxidant enzyme activities, inflammatory mediators, and apoptotic gene expression. Histopathological examination was performed. The involvement of PI3K\/Akt\/mTOR, p38 MAPK, and PTEN signaling pathways was assessed using molecular analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DOX administration caused significant ECG abnormalities, elevated serum cardiac biomarkers, increased lipid peroxidation, reduced antioxidant enzyme activities, enhanced inflammatory cytokine levels, and upregulated pro-apoptotic markers in cardiac tissue. Histological examination revealed marked myocardial degeneration. BCA treatment attenuated these alterations, with greater effects observed at the higher dose in several endpoints. It was associated with improved antioxidant status, reduced inflammatory and apoptotic marker expression, decreased p38 MAPK and PTEN immunoreactivity, and was associated with altered PI3K\/Akt\/mTOR and p38 MAPK pathway-marker immunoreactivity compared with the DOX group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Biochanin A alleviated acute DOX-induced cardiotoxicity in rats and was associated with modulation of oxidative stress, inflammatory, apoptotic markers, as well as, PI3K\/Akt\/mTOR and p38 MAPK pathway markers. BCA may therefore represent a potential cardioprotective adjunct strategy in acute anthracycline-associated cardiac injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1843282","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:45:49Z","timestamp":1783403149000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Biochanin A attenuates doxorubicin-induced cardiotoxicity in rats with associated modulation of PI3K\/Akt\/mTOR and p38 MAPK signaling"],"prefix":"10.3389","volume":"13","author":[{"given":"Mashael M.","family":"AlMutairi","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda M.","family":"AlKreathy","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasheed A.","family":"Shaik","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amani E.","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University","place":["Madinah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Magadmi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University","place":["Jeddah, Saudi 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