Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Comb Chem High Throughput Screen. 2021;24(5):701-715. doi: 10.2174/1386207323666201019145354.
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.
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.
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.
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.
在中医临床实践中，使用芪参益气方（QSYQ）治疗心血管疾病。然而，很少有研究探讨 QSYQ 是否影响肺动脉高压（PAH），以及 QSYQ 治疗 PAH 的作用机制和分子靶点尚不清楚。本研究采用基于生物信息学/网络拓扑的策略，鉴定 QSYQ 治疗 PAH 的生物活性成分、潜在靶点和分子机制。
采用网络药理学策略，通过整合活性成分收集、靶标预测、PAH 基因集、网络拓扑和基因富集分析，系统地探讨了多成分协同作用机制。
共鉴定出 QSYQ 的 107 种生物活性成分和 228 个成分靶点。此外，在 PAH 患者和对照组之间，鉴定出 234 个差异表达基因，其 |fold change| >2，调整后的 P 值 < 0.005，共鉴定出 266 个治疗靶点。通路富集分析表明，有 85 条通路显著富集，包括 PI3K-Akt、MAPK 和 HIF-1 信号通路。TP53 是核心靶基因，7 个其他关键基因（MAPK1、RELA、NFKB1、CDKN1A、AKT1、MYC 和 MDM2）是基于 QSYQ 对 PAH 的影响的基因通路网络中的关键基因。
基于网络药理学的综合研究可以阐明 QSYQ 治疗 PAH 的多成分协同作用机制，为进一步的动物实验、人类临床试验以及 QSYQ 的合理临床应用奠定基础。
