基于网络药理学探讨丹参-丹皮配伍抗脑缺血损伤的作用机制  

Investigation on the mechanism of Salviae Miltiorrhizae-Cortex Moutan against cerebral ischemic injury based on network pharmacology

作　　者：张娟利 李骅 王文军 黄少杰 马阳 丁一 文爱东 ZHANG Juan-li;LI Hua;WANG Wen-jun;HUANG Shao-jie;MA Yang;DING Yi;WEN Ai-dong(Department of Pharmacy,the First affiliated Hospital of Air Force Military Medical University,Xi’an 710032,China;China School of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]空军军医大学第一附属医院药剂科,西安710032 [2]陕西中医药大学药学院,咸阳712046

出　　处：《天然产物研究与开发》2021年第1期103-113,149,共12页Natural Product Research and Development

基　　金：国家自然科学基金(82074321,81602979,81703737)。

摘　　要：本文旨在通过网络药理学和分子对接方法探讨丹参-丹皮活性成分治疗脑卒中的潜在分子机制。首先基于中药系统药理学分析平台筛选丹参、丹皮的活性成分及其作用靶点,利用CTD、TTD和GeneCards数据库收集脑卒中相关靶点。然后将药物和疾病靶点取交集,借助STRING数据库获取靶点间相互作用关系,利用R语言的ClusterProfiler包对其进行生物功能和通路富集分析。最后,通过Cytoscape软件构建蛋白质-蛋白质相互作用和成分-靶点-通路网络图,并利用AutoDock Vina软件对网络中的关键靶点及对应成分进行分子对接验证。结果显示丹参-丹皮成分作用于脑卒中的靶点67个,GO分析显示其主要参与脂多糖应答,细菌来源的分子反应,氧化应激等生物学过程。KEGG通路富集共得到149条通路(P<0.05),主要涉及AGE-RAGE信号通路、IL-17信号通路、TNF信号通路等。分子对接结果显示,筛选的主要活性成分与其对应靶蛋白均具有较好的结合活性。综上,本研究通过网络药理学预测了丹参-丹皮治疗脑卒中可能的药效物质基础及其作用机制,为进一步挖掘其药效成分和临床扩大使用范围提供科学依据。This study aims to explore the effective material,potential targets and molecular mechanisms of Salviae Miltiorrhizae-Cortex Moutan(SM-CM)in treatment of stroke by network pharmacology and molecular docking.Firstly,the active components and their action targets of SM-CM were screened from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),and the targets for stroke were searched in the CTD,TTD and GeneCards databases.The common targets between the drug and disease were taken as the targets of SM-CM in the treatment of stroke.Then,the interaction relationship of common targets were obtained through the STRING database,and the protein-protein interaction(PPI)network and the component-target network were constructed by Cytoscape.The ClusterProfiler package of R language was used for GO functional and KEGG pathway enrichment analysis(P<0.05),and then the software of Cytoscape was used to build the network of component-target-pathway for visualization.Finally,the key targets and corresponding components in the network were verified by molecular docking in Autodock vina.A total of 67 potential targets were obtained in the treatment of stroke.GO analysis showed that it was mainly involved in response to lipopolysaccharide,response to molecule of bacterial origin,response to oxidative stress and others.KEGG pathway enrichment analysis obtained 149 signaling pathways,mainly involving in AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathways,TNF signaling pathways.In addition,the combined activity of the key components with their potential targets were all excellent,and comparing with the results of potential targets with their original ligands.In conclusion,we have confirmed the pharmacodynamic material basis and possible mechanisms of SM-CM in the treatment of stroke by network pharmacology,which will provide scientific basis for further screening its pharmacodynamic components and expanding the scope of clinical use.

关 键 词：网络药理学 分子对接 丹参-丹皮 脑卒中 作用机制 

分 类 号：R285[医药卫生—中药学]