Background and Objective: Qishen Yiqi formula (QSYQ) is used to treat cardiovascular
disease in the clinical practice of traditional Chinese medicine. However, few studies have explored
whether QSYQ affects pulmonary arterial hypertension (PAH), and the mechanisms of action and molecular
targets of QSYQ for the treatment of PAH are unclear. A bioinformatics/network topology-based strategy was
used to identify the bioactive ingredients, putative targets, and molecular mechanisms of QSYQ in PAH.
Methods: A network pharmacology-based strategy was employed by integrating active component
gathering, target prediction, PAH gene collection, network topology, and gene enrichment analysis
to systematically explore the multicomponent synergistic mechanisms.
Results: In total, 107 bioactive ingredients of QSYQ and 228 ingredient targets were identified.
Moreover, 234 PAH-related differentially expressed genes with a |fold change| >2 and an adjusted
P value < 0.005 were identified between the PAH patient and control groups, and 266 therapeutic
targets were identified. The pathway enrichment analysis indicated that 85 pathways, including the
PI3K-Akt, MAPK, and HIF-1 signaling pathways, were significantly enriched. TP53 was the core
target gene, and 7 other top genes (MAPK1, RELA, NFKB1, CDKN1A, AKT1, MYC, and
MDM2) were the key genes in the gene-pathway network based on the effects of QSYQ on PAH.
Conclusion: An integrative investigation based on network pharmacology may elucidate the
multicomponent synergistic mechanisms of QSYQ in PAH and lay a foundation for further animal
experiments, human clinical trials and rational clinical applications of QSYQ.