Qishen Yiqi Dripping Pills ameliorate doxorubicin-induced cardiotoxicity: a study based on bioinformatics and experimental verification.

Qishen Yiqi Dripping Pills (QSYQ) have shown promising therapeutic effects on cardiovascular diseases. Recent studies have reported their potential in mitigating doxorubicin-induced cardiotoxicity (DIC), but the primary active ingredients and specific mechanisms remain unclear. A total of 2740 differentially expressed genes (DEGs) were screened out. GSEA results were mainly enriched in Glycolysis, Apoptosis, Cellular Senescence, PI3K/Akt Signaling Pathway, TGF Beta Signaling Pathway, etc. Weighted gene co-expression network analysis yielded 1520 key module genes, and 1134 DIC-related genes were obtained by intersecting with DEGs. A total of 130 active ingredients and 943 target genes of QSYQ were obtained, and 50 common targets were identified after intersecting with DIC-related genes. The top 5 active ingredients were DFV, quercetin, Vestitone, formononetin and (6aR,11aR)-9,10-dimethoxy-6a,11a-dihydro-6H-benzofurano[3,2-c]chromen-3-ol. GO and KEGG enrichment analyses showed a close relationship with the HIF-1 signaling pathway and its upstream and downstream components. Three key genes identified were EP300, JUN, and CREBBP. Receiver operating characteristic analysis demonstrated good diagnostic value for these key genes, and their DOX-induced expression alterations were reversed by QSYQ (limited experimental evidence). Notably, the experimental validation of JUN showed a trend opposite to that observed in the bioinformatics analysis. Molecular docking revealed good binding capabilities of the primary active ingredients with the key genes. QSYQ may alleviate DIC through EP300, JUN, and CREBBP, providing new evidence for the use of QSYQ in ameliorating DIC.