Yixinyuan Gaofang ameliorates myocardial infarction in rats by inhibiting the TNF/NF-κB pathway.

Myocardial infarction (MI) is a severe cardiovascular disease with complex pathogenesis, in which inflammatory responses and oxidative stress play critical roles. Yixinyuan Gaofang (YXYGF) is a novel traditional Chinese medicine (TCM) formulation, and its effects and mechanisms in MI remain incompletely understood. MI was induced in rats via ligation of left anterior descending (LAD) coronary artery. Rats received intragastric administration of YXYGF at different dosage, and cardiac function was evaluated using echocardiography and hemodynamic measurements. Histological assessments included 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin-eosin (HE), and Masson staining to observe infarct size, tissue injury, and fibrosis. Serum biomarkers of myocardial injury were measured. Enzyme-linked immunosorbent assay (ELISA) and biochemical assays quantified myocardial inflammatory cytokines and oxidative stress markers. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) identified YXYGF chemical constituents, and network pharmacology analysis predicted potential signaling pathways. Tumor necrosis factor/nuclear factor-κB (TNF/NF-κB) pathway-related proteins were examined using Western blotting. YXYGF at different dosage all significantly improved left ventricular function in MI rats and markedly reduced infarct size, alleviated myocardial injury and fibrosis. In addition, YXYGF also inhibited inflammatory cytokine production and oxidative stress. UHPLC-MS identified 365 chemical components of YXYGF, of which 179 met the pharmacodynamic screening criteria. Mechanistic analysis suggested that the protective effects of YXYGF were closely associated with inflammatory response, hypoxia response, coagulation, and cardiovascular-related signaling pathways, with the TNF/NF-κB pathway identified as a key mechanism. Further mechanistic verification revealed that the NF-κB activator PMA could partially reverse the protective effects of YXYGF on cardiac function, myocardial function, histopathological damage, and oxidative inflammatory microenvironment in rats with myocardial infarction. YXYGF effectively improves cardiac dysfunction, reduces infarct size, fibrosis, and inflammatory and oxidative responses in MI rats, at least partially through inhibition of the TNF/NF-κB signaling pathway. These findings provide experimental evidence supporting the therapeutic application of YXYGF in cardiovascular disease prevention and treatment. However, these findings are based on an animal model, and further clinical studies are required to validate the therapeutic potential of YXYGF in humans.