{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:17:57Z","timestamp":1788848277868,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Myocardial hypertrophy represents a pathological cardiac adaptation involving abnormal cardiomyocyte enlargement that compromises ventricular function and precipitates heart failure. The flavonoid compound 5,7,4\u2032\u2010trimethoxy flavanone exhibits significant anti\u2010inflammatory and antioxidant activities, highlighting its potential as a phytocompound with desired pharmacological value for managing hypertrophic cardiac conditions. This investigation examined the cardioprotective effects of 5,7,4\u2032\u2010trimethoxy flavanone against isoproterenol\u2010induced myocardial hypertrophy in Swiss albino mouse models. Treatment with this flavonoid significantly reduced cardiac mass and myocyte diameter. As a result, expression levels of hypertrophic biomarkers such as ANP, BNP, calcineurin, and GATA4 in isoproterenol\u2010challenged animals were also markedly decreased. Additionally, 5,7,4\u2032\u2010trimethoxy flavanone administration diminished expression of oxidative stress markers and inhibited myocardial fibrosis development, as confirmed through Masson's trichrome histological evaluation. This mechanistic investigation revealed that this compound downregulated PI3K\/AKT signaling proteins while enhancing Nrf2\u2010mediated antioxidant pathways. These molecular effects resulted in inhibition of apoptosis and enhanced cellular survival, marked by elevated Bcl\u20102 and Bcl\u2010xL expression, as well as reduced caspase\u20103 enzymatic activity and decreased TUNEL\u2010positive cardiomyocytes. The experimental evidence supports the potential of 5,7,4\u2032\u2010trimethoxy flavanone as an effective adjunct for cardiac hypertrophy through its dual modulation of PI3K\/AKT and Nrf2 signaling networks. These findings establish 5,7,4\u2032\u2010trimethoxy flavanone as a promising cardioprotective agent, warranting further clinical development for hypertrophic cardiomyopathy treatment strategies.<\/jats:p>","DOI":"10.1002\/jbt.70821","type":"journal-article","created":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T16:46:41Z","timestamp":1774802801000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cardioprotective Role of 5,7,4\u2032\u2010Trimethoxy Flavanone Through PI3K\/AKT\u2010Nrf2 Signaling in Mice"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6354-4388","authenticated-orcid":false,"given":"Peramaiyan","family":"Rajendran","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, College of Science King Faisal University Al\u2010Ahsa Saudi 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