QiShenYiQi dripping pills ameliorate post-myocardial infarction cardiac fibrosis via modulation of the cAMP/Rap1 and PI3K/Akt signaling pathways.

Myocardial infarction (MI) is a multifactorial cardiovascular condition characterized by metabolic disturbances and inflammatory responses. QiShenYiQi dropping pills (QSYQ), a traditional Chinese medicine formula, have shown therapeutic potential through multi-component and multi-target mechanisms, yet their effects from the perspective of active compounds and metabolites remain underexplored. This study utilized phytochemical characterization, metabolomics, network pharmacology, molecular docking, and biological validation to investigate QSYQ's pharmacological mechanisms in MI treatment. Chemical constituents were identified via UHPLC-Q-Orbitrap HRMS, and plasma metabolites from MI rats were analyzed using UPLC-MS/MS. Network pharmacology and docking revealed 19 active components, 68 target proteins, and key pathways, including cAMP-Rap1 and PI3K-Akt, associated with QSYQ's effects. Experimental validation demonstrated that QSYQ significantly improved cardiac function, reduced myocardial fibrosis, and modulated key pathway proteins, including Cyclin D1. A two-week regimen proved more effective than one week. Enrichment analysis highlighted QSYQ's role in regulating cell proliferation and survival, supported by changes in 45 plasma metabolites. Molecular docking confirmed interactions between active components and targets, and biological validation reinforced the importance of cAMP-Rap1 and PI3K-Akt pathways. This study provides a systematic framework for understanding the therapeutic mechanisms of QSYQ, emphasizing its potential in addressing cardiac dysfunction and myocardial fibrosis in MI.