基于网络药理学及分子对接技术分析清眩降压汤治疗高血压的作用机制

Mechanism of Qingxuan Jiangya Decoction in Treatment of Hypertension Based on Network Pharmacology and Molecular Docking

目的 基于网络药理学和分子对接技术探讨清眩降压汤治疗高血压(HTN)的作用机制。方法利用TCMSP、ETCM和DrugBank等数据库筛选清眩降压汤的活性成分和作用靶标,通过GeneCards、DisGeNET和TTD数据库获取HTN作用靶标,并与清眩降压汤作用靶标相映射获取交集靶标;利用Cytoscape 3.7.1软件绘制活性成分-交集靶标网络图以及交集靶标蛋白互作(PPI)网络图,并分别根据度值以及接近中心性、中介中心性和度值筛选出主要活性成分和关键靶标;利用Metascape数据库对交集靶标进行GO生物功能分析及KEGG通路富集分析,最后利用AutoDock Vina软件进行清眩降压汤主要活性成分和关键靶标的分子对接。结果 获取清眩降压汤活性成分142个和作用靶标364个,HTN作用靶标2 313个,交集靶标231个;主要活性成分20个,如槲皮素、山柰酚和β-谷甾醇等;关键靶标21个,如MAPK1、SRC和AKT1等;GO生物功能分析提示清眩降压汤参与氧化还原酶活性、蛋白质同二聚化活性、蛋白域特异性结合等生物学过程,KEGG通路富集分析得到210条信号通路,涉及MAPK、TNF、HIF-1和PI3K/Akt信号通路等;分子对接验证了清眩降压汤主要活性成分和关键靶标之间的结合活性,二者结合度较高,构象稳定。结论 清眩降压汤可能通过MAPK、TNF、HIF-1和PI3K/Akt信号通路对细胞凋亡、炎症反应和氧化应激等生物学过程进行调控,从而达到治疗HTN的目的。

Objective: To explore the mechanism of Qingxuan Jiangya Decoction in the treatment of hypertension(HTN) Based on network pharmacology and molecular docking. Methods: TCMSP, ETCM, DrugBank databases etc. were used to screen the active ingredients and targets of Qingxuan Jiangya Decoction. The target of HTN was obtained through GeneCards, DisGeNET and TTD databases, and the intersection target was obtained by mapping with the target of Qingxuan Jiangya Decoction. Cytoscape 3.7.1 software was used to construct the active ingredient-intersection target network diagram and the intersection target protein interaction(PPI) network diagram, and the main active ingredients and key targets were selected according to the degree value and closeness centrality, betweenness centrality and degree respectively. Metascape database was used to analyze the GO biological function analysis and KEGG pathway enrichment analysis of the intersection targets. Finally, the molecular docking of the main active components and key targets of Qingxuan Jiangya decoction was carried out by using AutoDock Vina software. Results: There were 142 active ingredients and 364 targets of Qingxuan Jiangya Decoction were screened out, 2313 HTN targets and 231 intersection targets were obtained. 20 main active ingredients were obtained, such as quercetin, kaempferol, β-sitosterol, etc.;and 21 key targets were obtained, such as MAPK1,SRC, AKT1, etc. GO biological function analysis showed that Qingxuan Jiangya Decoction participates in biological processes such as oxidoreductase activity, protein homodimerization activity, and protein domain specific binding. KEGG pathway enrichment analysis obtained 210 signal pathways, which involved MAPK, TNF, HIF-1 and PI3K-Akt signal pathway, etc. The binding activity between the main active components and key targets was verified by molecular docking, which have a high degree of binding and a stable conformation. Conclusion: Qingxuan Jiangya decoction may regulate biological processes such as apoptosis, inflammatory response and oxidative stress through MAPK, TNF, HIF-1 and PI3K-Akt signal pathway, so as to achieve the purpose of treating HTN.