{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:01:59Z","timestamp":1790960519811,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"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: Post-myocardial infarction (MI) heart failure (HF) is characterized by myocardial energy metabolism disorder, with excessive glycolysis playing a key role in its progression. Silybin (SIL), a flavonoid derived from Silybum marianum, has demonstrated hepatoprotective and metabolic regulatory effects. However, the role of this flavonoid in ameliorating post-myocardial infarction heart failure (post-MI HF) by modulating energy metabolism remains unclear. Methods: This study employed an oxygen\u2013glucose deprivation (OGD) model to induce myocardial cell injury in vitro, with YC-1 treatment used to inhibit hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) for mechanistic validation. A myocardial infarction-induced HF mouse model was used for in vivo experiments. Results: In vitro, SIL enhanced cell viability, increased ATP levels, and decreased lactate production and reactive oxygen species (ROS) accumulation in OGD-treated myocardial cells. SIL downregulated the mRNA and protein expression of HIF-1\u03b1, 6-phosphofructo-2-kinase\/fructose-2,6-biphosphatase 3 (PFKFB3), glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA) while inhibiting HIF-1\u03b1 nuclear translocation. Furthermore, SIL suppressed glycolytic proteins (PFKFB3, GLUT1, and LDHA) in a manner comparable to the HIF-1\u03b1 inhibitor YC-1. This confirms that SIL\u2019s inhibition of glycolysis is HIF-1\u03b1-dependent. In vivo, SIL treatment improved cardiac function parameters (LVEF and LVFS) and attenuated left ventricular remodeling (LVID;d and LVID;s) in post-MI HF mice. Additionally, myocardial fibrosis markers were significantly reduced, accompanied by a decrease in the myocardial mRNA and protein expression of glycolytic proteins, including HIF-1\u03b1, PFKFB3, GLUT1, and LDHA. Conclusions: Silybin effectively ameliorates post-myocardial infarction heart failure through the HIF-1\u03b1-mediated regulation of glycolysis, leading to improved myocardial energy metabolism and enhanced cardiac function.<\/jats:p>","DOI":"10.3390\/nu17172800","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T15:03:14Z","timestamp":1756393394000},"page":"2800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Silybin Mitigates Post-Myocardial Infarction Heart Failure in Mice via Modulation of HIF-1\u03b1-Driven Glycolysis and Energy Metabolism"],"prefix":"10.3390","volume":"17","author":[{"given":"Mengyuan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Chen","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"}]},{"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":"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":"Xiao","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":"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":"Haowen","family":"Zhuang","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":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1093\/cvr\/cvac013","article-title":"Global burden of heart failure: A comprehensive and updated review of epidemiology","volume":"118","author":"Savarese","year":"2023","journal-title":"Cardiovasc. 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