Energy metabolism disorders play a crucial role in the progression of heart failure following myocardial infarction, however, current mainstream therapies primarily focus on the renin-angiotensin system, and the precise molecular mechanisms and active ingredients by which Yangxinshi Tablet improves myocardial energy metabolism remain unclear.
Here, we elucidate the cardioprotective effects of Yangxinshi Tablet in a post-MI heart failure rat model and in vitro hypoxic cardiomyocytes, and demonstrate that it restores energy homeostasis by inhibiting the FOXO1/PDK4 signaling pathway, up-regulating OGDH expression, promoting the TCA cycle, and increasing ATP levels. Integrated with multi-omics, molecular docking, and cellular assays, we further identify senkyunolide H, apigenin, astragaloside IV, and astragaloside VII as the primary active constituents responsible for these effects, which directly target and bind to FOXO1, PDK4, and OGDH to improve mitochondrial respiration.
This work provides a comprehensive theoretical foundation elucidating the critical role of the FOXO1/PDK4 axis in heart failure energy metabolism and clarifies the active substance basis of Yangxinshi Tablet. The work entitled “Yangxinshi Tablet protects against post-myocardial infarction heart failure with reduced ejection fraction by improving energy metabolism through inhibition of FOXO1/PDK4 signaling” was published on Chinese Journal of Natural Medicines (published on May 20, 2026).
DOI: 10.1016/S1875-5364(26)61119-3