基于网络药理学的葛根素治疗动脉粥样硬化潜在分子机制研究  

Potential Molecular Mechanisms of Puerarin in Treatment of Atherosclerosis Based on Network Pharmacology

作　　者：何信用 王俊岩 宋囡[1] 贾连群[1] 杨关林[1] 陈文娜[1] 张哲[1] HE Xinyong;WANG Junyan;SONG Nan;JIA Lianqun;YANG Guanlin;CHEN Wenna;ZHANG Zhe(L.iaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;Guangzhou University of Chinese Medicine,Guangzhou 510405,Guandong,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]广州中医药大学,广东广州510405

出　　处：《中华中医药学刊》2020年第9期116-120,I0014,I0015,共7页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金(81874372);辽宁省自然科学基金指导计划(20170520206);辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金(zyzx1501,zyzx1902)。

摘　　要：目的通过网络药理学方法探讨葛根素(puerarin)治疗动脉粥样硬化(AS)潜在的分子生物学机制。方法从PubChem数据库找出葛根素SDF、Mol2、Canonical SMILES号,从中药系统药理学分析平台(TCMSP)、SwissTargetPrediction、SEA、STITCH数据库查找所有葛根素潜在的作用靶点,并构建成分-靶点网络;通过Therapeutic Target Database、DrugBank以及DisGeNET数据库查找与AS相关的靶点,并将葛根素与AS靶点进行映射;利用STRING平台对映射的靶点进行蛋白质-蛋白质相互作用网络的构建,并筛选核心靶点;对核心靶点进行网络分析,同时利用DAVID数据库对核心靶点蛋白进行GO生物学功能(MF)、生物学过程(BP)、细胞学组分(CC)及KEGG通路富集分析,结果进行数据可视化处理,并构建葛根素-靶点-信号通路多维网络。结果以"puerarin"的不同表现格式(SDF、Mol2、Canonical SMILES号)为筛选条件,整合上述分子靶点数据,共得到103个潜在靶点;以"atherosclerosis"为检索词,从3个疾病数据库共得到175个与AS相关的靶点。通过STRING平台筛选出NOS2、NOS3、HMOX1、VEGFA、IL6、STAT3等21个核心靶点。GO注释分析确定161条BP信息,主要涉及到一氧化氮生物合成过程的正调控、炎症反应、氧化还原过程、NF-κB信号传导的阳性调节、凋亡过程的正负调节等;16条CC信息,主要涉及到蛋白质细胞外基质、RNA聚合酶Ⅱ转录因子复合物、质膜等;26条MF信息,主要涉及到蛋白质结合、RNA聚合酶II转录因子活性、丝氨酸型内肽酶活性、花生四烯酸盐15-脂氧和酶活性、一氧化氮合成酶活性等。KEGG富集分析结果显示有34条通路与AS相关,主要包括HIF-1信号通路、TNF信号通路、NF-κB信号通路、血管内皮生长因子信号通路、钙信号通路、PI3K-Akt信号通路等。结论葛根素通过多靶点协作调控多种信号通路共同参与到抑制炎症反应的过程,从而达到治疗AS的目的。为葛根素的基Objective To explore the potential molecular biological mechanism of puerarin in the treatment of atherosclerosis(AS)by means of network pharmacology.Methods We found the SDF,Mol2 and Canonical SMILES numbers of puerarin from PubChem Database.By identifying all potential targets of puerarin from TCMSP,Swiss Target Prediction,SEA and STITCH databases,we constructed ingredients-targets network.We retrieved AS-related targets through TTD,DrugBank and DisGeNET databases,and mapped the targets between puerarin and AS.Using STRING platform to construct PPI network and screen core targets.The DAVID database was used to analyze the biological functions(MF),biological processes(BP),cytological components(CC)and KEGG pathway enrichment of core target proteins,to visualize the results and further to construct a multi-dimensional network of puerarin-targets-signal pathways.Results Using the different expression formats of"puerarin"(SDF,Mol2,Canonical SMILES)as screening conditions,103 potential targets were obtained by integrating the above data of molecular and targets.Using"atherosclerosis"as a qualifier,175 AS-related targets were obtained from three disease databases.Through STRING platform,21 core targets such as NOS2,NOS3,HMOX1,VEGFA,IL6 and STAT3 were screened.GO identified 161 BP information,mainly related to the positive regulation of nitric oxide biosynthetic process,inflammatory response,redox process,positive regulation of NF-κB signal transduction,positive and negative regulation of apoptotic process,etc.A total of 16 terms of CC information,mainly involved protein extracellular matrix,RNA polymerase II transcription factor complex,plasma membrane,etc.A total of 26 terms of MF information were mainly related to protein binding,RNA polymeraseⅡtranscription factor activity,serine-type endopeptidase activity,arachidonate 15-lipoxygenase activity,nitric-oxide synthase activity,etc.KEGG enrichment analysis showed that 34 pathways were associated with AS,including HIF-1 signaling pathway,TNF signaling pathway,NF-κ

关 键 词：网络药理学 葛根素 动脉粥样硬化 分子机制 

分 类 号：R259.435[医药卫生—中西医结合]