Mechanism of Danggui Buxue decoction in the treatment of myocardial infarction based on network pharmacology and experimental identification

Background: Myocardial infarction (MI) remains one of the major causes of high morbidity and mortality worldwide. Danggui Buxue Decoction (DBD)-an ancient Chinese herbal decoction-has been used to prevent coronary heart disease, which was called "chest palsy" in ancient clinics. However, the mechanism of DBD in the treatment of MI remains unclear. The aim of this study was to explore the effect and mechanism of DBD on MI by combining network pharmacology with in vivo experiments. Materials and methods: First, public databases were used to identify the key active chemicals and possible targets of DBD. The MI targets were obtained from the Therapeutic Target Database, and the function of the target genes in relation to linked pathways was investigated. Subsequently, Cytoscape software was used to build a target-signaling pathway network. Finally, the efficacy of DBD therapy on MI was validated using in vivo investigations combined with molecular docking. Results: In traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), 27 bioactive compounds were screened from DBD. A total of 213 common targets were obtained, including 507 DBD targets and 2566 MI targets. Enrichment analysis suggests that PI3K/AKT is a potential signaling pathway for DBD-based protection. Immunofluorescence and protein blotting confirmed PI3K/AKT1, ERK2, and CASPASE-9 as the target proteins. Molecular docking analysis showed that quercetin, kaempferol, isoflavanones, isorhamnetin, hederagenin, and formononetin had high binding affinity to AKT1, ERK2, and CASPASE-9. Conclusions: This study demonstrated that the therapeutic benefit of DBD on MI may be mediated via target proteins in the PI3K/AKT pathway, such as AKT1, ERK2, and CASPASE-9. Our study data can help to provide ideas and identify new treatment targets for MI.