Exploring the mechanism of Yi Qi Huo Xue compound prescription in treating chronic heart failure based on integrated network pharmacology and transcriptomics

Background Chronic heart failure (CHF) represents a major global health burden characterized by complex pathologies. The Yi Qi Huo Xue compound prescription (YQHXCP) has demonstrated significant clinical efficacy in alleviating heart failure symptoms; however, its precise molecular mechanisms remain obscure. Objective This study aims to elucidate the core targets and biological pathways of YQHXCP in treating CHF through an integrated approach combining network pharmacology with transcriptomic validation. Methods A rat model of heart failure was established, and transcriptomic data were acquired via RNA sequencing. Concurrently, putative targets of YQHXCP were retrieved from the TCMSP and SwissTargetPrediction databases. Key targets were identified by intersecting differentially expressed genes (DEGs) from the animal model with predicted drug targets. Subsequently, functional enrichment analysis, gene-gene interaction (GGI) network construction, and molecular docking were employed to decipher the underlying mechanisms, followed by in vivo validation using RT-qPCR. Results Three pivotal target genes were identified: Top2a, Cdk1, and E2f2. Enrichment analysis revealed that YQHXCP primarily modulates mitochondrial protein complexes, ribosomal subunit assembly, and cell cycle checkpoints. Molecular docking demonstrated strong binding affinity between the active ingredient quercetin and both Cdk1 and E2f2 proteins. RT-qPCR confirmed that YQHXCP significantly reversed the downregulation of Cdk1 and E2f2 expression in the myocardial tissue of CHF rats. Conclusion YQHXCP may exert its anti-CHF effects by targeting Cdk1 and E2f2 to regulate mitochondrial function and cell cycle homeostasis. These findings provide novel insights into the multi-target therapeutic mechanisms of traditional Chinese medicine formulations.