灯盏生脉胶囊治疗缺血性脑卒中作用机制的网络药理学分析

Pharmacological Mechanism Analysis of Dengzhan Shengmai Capsule on Cerebral Ischemic Stroke by Network Pharmacology Approach

目的探讨灯盏生脉胶囊治疗缺血性脑卒中(Cerebral ischemic stroke,CIS)的网络药理学机制。方法应用中医百科全书(ETCM)及BATMAN-TCM数据库平台收集灯盏生脉胶囊的有效化学成分。利用PubChem、Stitch平台获取灯盏生脉胶囊活性成分的潜在靶点,通过DisGeNET平台获取缺血性脑卒中的疾病靶点基因,并遴选重合的靶点作为药物-疾病共同靶点。利用HPRD数据库及Cytoscape v3.6.0软件构建药物-疾病共同靶点蛋白-蛋白互作(PPI)网络,筛选出关键靶点和核心基因团簇。借助Metascape平台对所得关键靶点、核心团簇进行基因本体(GO)分析和京都基因和基因组百科全书(KEGG)通路富集分析。结果共获得灯盏生脉胶囊活性成分310个、预测靶点192个、疾病靶点393个、药物-疾病共同靶点28个、关键靶点211个,核心团簇包含22个靶点。其潜在作用机制与神经细胞凋亡、细胞增殖分化、DNA转录、蛋白质合成、酶结合等生物过程及分子功能有关。灯盏生脉胶囊治疗缺血性脑卒中关键靶点的核心通路包括丝裂原活化蛋白激酶(MAPK)信号通路、核因子κB(NF-κB)信号通路、内分泌抵抗、甲状腺激素信号通路、癌症通路等。结论灯盏生脉胶囊治疗缺血性脑卒中可能主要与其抑制炎症反应、调控内分泌代谢及癌症通路等有关。

Objective To explore the pharmacological mechanism of Dengzhan Shengmai capsule in the treatment of cerebral ischemic stroke by using a network pharmacology approach.Methods Network pharmacology database platforms(The Encyclopedia of Traditional Chinese Medicine and BATMAN-TCM)were used to collect the active chemical constituents of Dengzhan Shengmai capsule.PubChem and Stitch platform were used to obtain potential targets of the active chemical constituents.Then we used the DisGeNET database to obtain the target genes of cerebral ischemic stroke and select the coincidence targets as the drug-disease common targets.The constructive protein-protein interaction network map of the drug-disease common targets was constructed by HPRD database and Cytoscape v3.6.0 software,and the key targets and core clusters were screened out.Finally,Gene Ontology(GO)Analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were carried out with the help of Metascape analysis platform.Results A total of 310 active components and 192 predicted targets were obtained,with 393 disease targets and 28 drug-disease common targets.And 211 key targets were screened out while the core clusters contained 22 targets.The potential mechanism of biological processes and molecular function was related to nerve cell apoptosis,cell proliferation and differentiation,DNA transcription,protein synthesis,enzyme binding and so on.The core pathways of key targets involved in MAPK signal pathway,NF-κB signal pathway,endocrine resistance,thyroid hormone signaling pathway,pathways in cancer,and so on.Conclusion The effective mechanism of Dengzhan Shengmai capsule in the treatment of cerebral ischemic stroke is probably related to inhibiting inflammatory reaction,regulating endocrine metabolism and pathways in cancer and so on.