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Amentoflavone (AMF) has beneficial therapeutic effects against several cardiovascular diseases; however, its role and underlying mechanisms in pathological cardiac remodeling remain unclear. Here, we investigated the protective role of AMF against pathological cardiac remodeling in transverse aortic constriction (TAC)\u2010induced overloaded hearts. Mice with pressure overload caused by TAC were treated with AMF, and the effects of AMF on cardiac function, cardiac hypertrophy, and fibrosis were analyzed. RNA\u2010seq, molecular docking, surface plasmon resonance (SPR), and co\u2010IP were used to identify the downstream targets of AMF. Angiotensin II (Ang II) and transforming growth factor beta 1 (TGF\u2010\u03b21) were used to characterize the role of AMF and its downstream targets in cardiac hypertrophy and fibrosis in\u00a0vitro. Sustained AMF administration significantly suppressed TAC\u2010induced cardiac remodeling. Compared with those in TAC model mice, the heart\/body weight ratio, cardiomyocyte cross\u2010sectional area, and hypertrophic molecular markers were significantly lower in AMF\u2010treated TAC model mice. Moreover, TAC\u2010induced myofibroblast generation and extracellular matrix deposition were effectively reversed following AMF administration. Similar results were obtained after AMF treatment for cardiomyocyte hypertrophy and cardiac fibrosis in\u00a0vitro. Mechanistically, by directly binding to TGF\u2010\u03b2 receptor 1, AMF blocked the regulatory effect of TGF\u2010\u03b21 and inhibited the TGF\u2010\u03b2\/Smad and MAPK signaling pathways. These results suggest that AMF, through binding to TGF\u2010\u03b2 receptor 1, may be a promising therapeutic option for pathological cardiac remodeling.<\/jats:p>","DOI":"10.1002\/ptr.70248","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:47:06Z","timestamp":1770972426000},"page":"2380-2396","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Amentoflavone, a Preferentially\n                    <scp>TGF\u2010\u03b2<\/scp>\n                    Receptor 1 Inhibitor, Alleviates Cardiac Remodeling and Dysfunction Through Modulating the\n                    <scp>TGF\u2010\u03b2<\/scp>\n                    \/Smad and\n                    <scp>MAPK<\/scp>\n                    Signaling Pathways"],"prefix":"10.1002","volume":"40","author":[{"given":"Jiangjiao","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Daping Hospital The Third Military Medical University (Army Medical University)  Chongqing China"},{"name":"Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Ministry of Education  Chongqing China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center Chongqing Institute of Cardiology  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital The Third Military Medical University (Army Medical University)  Chongqing China"},{"name":"Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Ministry of Education  Chongqing China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center Chongqing Institute of Cardiology  Chongqing China"},{"name":"College of Bioengineering Chongqing University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital The Third Military Medical University (Army Medical University)  Chongqing China"},{"name":"Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Ministry of Education  Chongqing China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center Chongqing Institute of Cardiology  Chongqing China"},{"name":"Department of Cardiology 921 Hospital of Joint Logistics Support Force People's Liberation Army of China (The Second Affiliated Hospital of Hunan Normal University)  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital The Third Military Medical University (Army Medical University)  Chongqing 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Hospital The Third Military Medical University (Army Medical University)  Chongqing China"},{"name":"Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Ministry of Education  Chongqing China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center Chongqing Institute of Cardiology  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital The Third Military Medical University (Army Medical University)  Chongqing China"},{"name":"Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Ministry of Education  Chongqing China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center Chongqing Institute of Cardiology  Chongqing 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