Yangxin granules exert cardioprotective effects against acute myocardial infarction by modulating NF-κB to suppress ferroptosis.

Objectives: To investigate the therapeutic effects of Yangxin granules (YNX), a classic traditional Chinese medicine, in acute myocardial infarction (AMI) and its underlying mechanism. Methods: Rats were subjected to left anterior descending coronary artery ligation to establish AMI. Thereafter, YNX was administered once daily for 4 weeks. Cardiac function, histopathological changes, iron deposition, oxidative stress, and ferroptosis related proteins were evaluated. RNA sequencing was performed to identify differentially expressed genes and associated signaling pathways. H9c2 cells were treated with YNX in vitro under hypoxic conditions, followed by the supplementation of either a ferroptosis inducer or nuclear factor kappa B (NF-κB) activator. Cell viability, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS), iron, and ferroptosis and NF-κB pathway related proteins were measured. Results: YNX notably enhanced cardiac function, mitigated myocardial injury, alleviated fibrosis, and inhibited iron deposition and oxidative stress in AMI rats. Mechanistically, YNX suppressed ferroptosis by decreasing transferrin receptor 1 (TFR-1) and increasing anti-ferroptotic protein levels. Transcriptomic analysis and western blotting revealed that YNX inhibited NF-κB activity, which was derived from decreased phosphorylation of IκBα and NF-κB p65 inhibitor. In vitro assays revealed that 40 μg/mL YNX enhanced H9c2 cell proliferation, decreased LDH, ROS, and iron ion levels, downregulated ferroptosis-related proteins, and inhibited NF-κB pathway activation under hypoxic conditions. These effects were reversed when the cells were treated with a ferroptosis inducer or NF-κB pathway activator. Conclusions: YNX alleviates AMI by suppressing ferroptosis by inhibiting the NF-κB pathway, modulating iron metabolism, and mitigating oxidative stress.