J Ethnopharmacol. 2026 May 16:121798. doi: 10.1016/j.jep.2026.121798. Online ahead of print.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Yiqi Huoxue Lishui (tonifying qi, promoting blood circulation, and promoting diuresis to relieve water retention) is a core therapeutic principle in traditional Chinese medicine for the treatment of post-myocardial infarction heart failure (PMI-HF). Optimized New Shengmai Powder (ONSMP) is a traditional prescription composed of Astragalus mongholicus (Huangqi), Codonopsis pilosula (Dangshen) and other Chinese medicinal herbs. It has long been used in northern China to treat cardiovascular diseases such as "chest impediment" and heart failure characterized by qi deficiency, blood stasis and water retention according to traditional Chinese medicine theory. Clinical practice suggests that ONSMP can improve symptoms and cardiac function in such patients, but the modern pharmacological basis of its cardioprotective effects remains unclear. In recent years, ferroptosis-related oxidative injury has been recognized as a key mechanism driving the progression of PMI-HF. Whether ONSMP regulates this pathological process, and through which molecular pathways, remains to be elucidated.
AIM OF THE STUDY: To evaluate the protective effects of ONSMP on myocardial injury and ferroptosis in rats with heart failure after myocardial infarction, and to investigate whether these effects are mediated through regulation of the cGMP-PKG-GPX4 axis and redox homeostasis.
MATERIALS AND METHODS: A rat model of PMI-HF was established in male rats by left anterior descending coronary artery ligation. After successful model establishment, rats received ONSMP or vehicle. Cardiac function and remodeling were assessed by echocardiography and histological examination. Myocardial ferroptosis was evaluated based on ultrastructural changes and ferroptosis-related markers. Label-free quantitative proteomics was applied to screen key signaling pathways, and the cGMP-PKG-GPX4 axis-related molecules (AKT1, eNOS, sGCβ1, cGMP, PKG1, STAT3 and GPX4) as well as redox indices (cGMP, NO, GSH, MDA, 4-HNE and lipid peroxides) were further measured for validation.
RESULTS: Compared with the model group, ONSMP markedly improved left ventricular systolic function in rats with PMI-HF and attenuated myocardial hypertrophy, fibrosis and structural damage. ONSMP reduced myocardial ferroptosis, as evidenced by relatively preserved mitochondrial morphology and alleviated iron-dependent lipid peroxidation. Proteomic and biochemical analyses showed that ONSMP activated the cGMP-PKG-GPX4 axis, increased the phosphorylation of AKT1, eNOS, PKG1 and STAT3, upregulated GPX4 expression, elevated cGMP, NO and GSH levels, and decreased the accumulation of MDA, 4-HNE and lipid peroxides.
CONCLUSION: ONSMP improves cardiac function and attenuates myocardial injury in rats with PMI-HF, at least in part by activating the cGMP-PKG-GPX4 axis, suppressing myocardial ferroptosis, and restoring redox homeostasis. These findings provide mechanistic support for the traditional use of ONSMP in heart failure treatment.
PMID:42144210 | DOI:10.1016/j.jep.2026.121798