{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:04Z","timestamp":1787029204718,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82230126"],"award-info":[{"award-number":["82230126"]}]},{"name":"National Natural Science Foundation of China","award":["2022YFC3500100"],"award-info":[{"award-number":["2022YFC3500100"]}]},{"name":"National Key Research and Development Program of China","award":["82230126"],"award-info":[{"award-number":["82230126"]}]},{"name":"National Key Research and Development Program of China","award":["2022YFC3500100"],"award-info":[{"award-number":["2022YFC3500100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Abnormal mitochondrial energy metabolism is a key factor in the development and progression of cardiac hypertrophy. Hopeaphenol (HP), a tetramer of the natural polyphenol resveratrol, exhibits higher biological activity than resveratrol, but its specific role in cardiac hypertrophy and underlying mechanisms remains unclear. Methods: This study explored the protective effect and mechanism of hopeaphenol on cardiac hypertrophy through in vivo and in vitro experiments. In in vivo experiments, transverse aortic constriction (TAC) was used to induce cardiac hypertrophy in mice; HE, Masson, and WGA staining were applied to observe myocardial changes, ELISA was used to detect animal serum indicators, and the Cellular Thermal Shift Assay (CETSA) was conducted to verify the interaction between hopeaphenol and AMPK. In in vitro experiments, angiotensin II (Ang II) was used to induce hypertrophy of HL-1 cardiomyocytes, and the AMPK-specific inhibitor Compound C was employed to confirm the role of the AMPK pathway. Results: In in vivo experiments, TAC-induced cardiac hypertrophy in mice was characterized by left ventricular cavity enlargement and decreased ejection fraction; hopeaphenol treatment significantly improved these cardiac function indices, and HE, Masson, and WGA staining confirmed that hopeaphenol could restore cardiomyocyte morphology and reduce fibrosis. ELISA results of animal serum showed that hopeaphenol could improve metabolic disorders in TAC mice. Furthermore, CETSA confirmed a direct interaction between hopeaphenol and AMPK. In in vitro experiments, hopeaphenol reduced Ang II-induced hypertrophy and apoptosis of HL-1 cardiomyocytes, enhanced mitochondrial membrane potential, and decreased reactive oxygen species (ROS) levels by activating the AMPK pathway; moreover, the AMPK-specific inhibitor Compound C blocked these effects. This suggests that hopeaphenol\u2019s cardioprotective effect is largely mediated by AMPK activation. Conclusions: The protective effect of hopeaphenol on cardiac hypertrophy is highly dependent on the activation of the AMPK signaling pathway, with CETSA and molecular docking supporting direct binding between hopeaphenol and AMPK; this pathway improves mitochondrial dysfunction through AMPK, thereby alleviating heart failure caused by pressure overload. This finding identifies hopeaphenol as a potential candidate for further development in the prevention and treatment of heart failure.<\/jats:p>","DOI":"10.3390\/nu17183025","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T17:08:17Z","timestamp":1758560897000},"page":"3025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unlocking Hopeaphenol: A Potent Ally Against Cardiac Hypertrophy via AMPK Activation"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8665-1351","authenticated-orcid":false,"given":"Jinhong","family":"Chen","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8319-5189","authenticated-orcid":false,"given":"Chongkai","family":"Fang","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowen","family":"Zhuang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunping","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1113\/JP271301","article-title":"Mitochondrial dynamics, mitophagy and cardiovascular disease","volume":"594","author":"Pennanen","year":"2016","journal-title":"J. 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