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Harmine, a \u03b2\u2010carboline alkaloid found in plants, possesses numerous pharmacological functions, including alleviating cardiac hypertrophy. Similarly, Selenomethionine (SE), a primary organic selenium source, has been shown to mitigate cardiac autophagy and alleviate injury. To explores the therapeutic potential of combining Harmine with SE to treat cardiac hypertrophy. The synergistic effects of SE and harmine against cardiac hypertrophy were assessed in\u00a0vitro with angiotensin II (AngII)\u2010induced hypertrophy and in\u00a0vivo using a <jats:italic>Myh6<\/jats:italic><jats:sup><jats:italic>R404Q<\/jats:italic><\/jats:sup> mouse model. Co\u2010administration of SE and harmine significantly reduced hypertrophy\u2010related markers, outperforming monotherapies. Transcriptomic and metabolic profiling revealed substantial alterations in key metabolic and signalling pathways, particularly those involved in energy metabolism. Notably, the combination therapy led to a marked reduction in the activity of key glycolytic enzymes. Importantly, the addition of the glycolysis inhibitor 2\u2010deoxy\u2010D\u2010glucose (2\u2010DG) did not further potentiate these effects, suggesting that the antihypertrophic action is predominantly mediated through glycolytic inhibition. These findings highlight the potential of SE and harmine as a promising combination therapy for the treatment of cardiac hypertrophy.<\/jats:p>","DOI":"10.1111\/jcmm.70124","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T08:34:53Z","timestamp":1727771693000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The enhancing effects of selenomethionine on harmine in attenuating pathological cardiac hypertrophy via glycolysis metabolism"],"prefix":"10.1111","volume":"28","author":[{"given":"Qi","family":"Chen","sequence":"first","affiliation":[{"name":"Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu P. R. 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