基于系统药理学分析三七总皂苷干预脑血管疾病的作用机制

Mechanism of Action of Panax notoginseng Saponins in the Intervention of Cerebrovascular Diseases: An Analysis Based on Systems Pharmacology

目的采用系统药理学方法,研究三七总皂苷(Panax notoginseng saponins, PNS)干预脑血管疾病的分子网络机制。方法首先通过文本挖掘系统挖掘PNS关联的主要疾病,然后通过多数据库联合检索PNS主要有效成分的作用靶点和脑血管疾病相关靶点;使用Cytoscape 3.2.1软件构建有效成分-作用靶点-通路-疾病网络、作用靶点蛋白-蛋白相互作用网络以及疾病靶点蛋白-蛋白作用网络,并对两个蛋白网络进行交叉融合,筛选出核心网络,对核心网络进行进一步分析和筛选。在此基础上,利用Cytoscape的插件ClueGO对核心靶点进行生物过程和通路的富集分析,综合结果和文献检索预测作用机制。结果检索得到6种主要有效成分的预测靶点194个以及脑血管疾病相关靶点353个,通过筛选得到PNS干预脑血管疾病的潜在靶点232个,核心靶点富集分析结果提示,PNS可能参与脑血管疾病中氧化应激、炎症反应、凋亡以及血管新生的调控,并且通过调控FGFR信号通路、凋亡途径、ERBB2信号通路、神经营养因子和VEGF信号通路、IL-10信号通路和炎症小体信号通路,在脑血管疾病中发挥保护作用。结论结果为进一步深入研究PNS干预脑血管疾病的药理机制提供了重要依据。

Objective To investigate the molecular network mechanism of Panax notoginseng saponins 0PNS） in the intervention of cerebrovascular diseases based on systems pharmacology. Methods Firstly, text mining was used to identify- the diseases associated with PNS, and then text mining and search of muhiple databases were performed to obtain 194 putative targets of 6 major effective constituents and 353 targets associated with cerebrovascular diseases. The association between putative targets and cerebral isehemia was analyzed. Cytoseape 3.2.1 was used to construct effective constituent-putative target- pathway-disease network, putative target protein-protein interaction network, and disease target protein-protein interaction network, and the two protein networks were crossed and integrated to screen out core networks. The core networks were analyzed and screened. A total of 232 potential core targets involved in the intervention of cerebrovascular diseases by PNS were obtained. ClueGO, a plug-in of Cytoscape, was used for the enrichment analysis of biological processes and pathways for these core targets. Mechanism of action was predicted with reference to the above results and literature search. Results PNS might be involved in the regulation of oxidative stress, inflammatolT- response, apoptosis, and angiogenesis in cerebrovascular diseases. It exerted a protectiveettect against cerebrovascular diseases by regulating the FGFR signaling pathway, apoptosis pathway, ERBB2 signaling pathway, neurtrotrophin and VEGF signaling pathways, IL-10 signaling pathway, and intlammasonle signaling pathway. Conclusion The results of this study provide an important basis for thrther research on the pharmacological meehanisnl of PNS in the treatment of eerebrovaseular diseases.