Elucidation of the Mechanisms and Molecular Targets of Qishen Yiqi Formula for the Treatment of Pulmonary Arterial Hypertension using a Bioinformatics/Network Topology-based Strategy

Peiliang       Wu; Xiaona       Xie; Mayun       Chen; Junwei       Sun; Luqiong       Cai; Jinqiu       Wei; Lin       Yang; Xiaoying       Huang; Liangxing       Wang
doi:10.2174/1386207323666201019145354
Abstract

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.
Keywords: Qishen Yiqi formula, pulmonary arterial hypertension, network pharmacology, bioinformatics, mechanism, gene ontology.
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DOI https://dx.doi.org/10.2174/1386207323666201019145354	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402
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