{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:49:53Z","timestamp":1792511393383,"version":"4.5.0"},"reference-count":64,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"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":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Arsenic trioxide (ATO) is an effective chemotherapeutic agent but causes severe cardiotoxicity, which limits its clinical application. 10\u2010Gingerol (10Gin) is a major bioactive component of ginger, yet its cardioprotection and the mechanism underlying its effects against ATO\u2010induced heart injury (HI) have not been fully elucidated. This study integrated network pharmacology (NP) analysis, in\u00a0vivo mouse models, and in\u00a0vitro cell experiments to investigate the cardioprotection of 10Gin against ATO\u2010induced HI and its underlying mechanisms. NP analysis identified 32 overlapping therapeutic targets of 10Gin, ATO, and HI, among which the phosphoinositide 3\u2010kinase\/protein kinase B (PI3K\/AKT) pathway was the most significantly enriched cardiovascular\u2010related pathway. Our in\u00a0vivo experimental results demonstrated that 10Gin treatment significantly ameliorated ATO\u2010induced histopathological injury and cardiac dysfunction in mice. Echocardiographic evaluation showed that 10Gin improved ATO\u2010induced systolic dysfunction, as evidenced by increased ejection fraction and fractional shortening. Specifically, 10Gin reduced serum levels of myocardial injury markers, enhanced endogenous antioxidant enzyme activities, decreased reactive oxygen species production, downregulated pro\u2010inflammatory cytokine mRNA expression, and inhibited cardiomyocyte apoptosis. In\u00a0vitro experiments involving H9c2 cells and AC16 human cardiomyocytes showed that 10Gin enhanced cell viability, attenuated apoptosis and oxidative stress, thereby exerting cardioprotective effects. Moreover, 10Gin significantly increased the p\u2010PI3K\/PI3K and p\u2010AKT\/AKT ratios both in\u00a0vivo and in\u00a0vitro. Notably, the in\u00a0vitro cardioprotection of 10Gin could be partly reversed by the PI3K inhibitor LY294002. These findings indicate that 10Gin alleviates ATO\u2010induced HI through antioxidant, anti\u2010inflammatory, and anti\u2010apoptotic mechanisms, which are likely mediated by PI3K\/AKT activation, thereby supporting further investigation of 10Gin as a potential adjunctive candidate.<\/jats:p>","DOI":"10.1002\/fsn3.72180","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:17:53Z","timestamp":1785302273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["10\u2010Gingerol Alleviates Arsenic Trioxide\u2010Induced Cardiotoxicity: Mechanisms Involving the\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    Pathway Revealed by Network Pharmacology and Experimental 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