摘要
目的基于网络药理学和分子对接技术探究当归治疗轻度认知功能障碍(MCI)的关键作用靶点。方法采用TCMSPW、SwissTargetPrediction、UniProt等数据库检索当归的有效成分,并得到相应靶点;再通过DisGeNET、GeneCards等数据库检索轻度认知功能障碍的相关靶点,使用Venny2.1.0平台对当归和轻度认知功能障碍相关靶点取交集,并构建韦恩图。再使用Cytoscape3.9.1软件建立可视化蛋白互作网络(PPI),再利用David数据库和微生信网站进行GO富集分析和KEGG通路与基因功能富集分析及网络可视化,最后通过AutoDock Tools进行分子对接验证。结果当归关键基因有44种共同基因,包括NPC1L1、NR1H3、RORC、ESR1、ESR2、SHBG等,MCI关键基因有3190个,包括APOE、SPG11、PAH、MAPT、SCN8A、APP等。取交集后当归和MCI相关基因共有25个交集,包括ESR1、ESR2、SHBG、HMGCR、CYP19A1、AR、CYP17A1等,其中PPI显示的关键靶点按MCC值排序,前10位依次为CYP19A1、CYP17A1、ESR1、SHBG、AR、NR3C1、ESR2、HSD11B1、PPARG、PPARA。GO分析提示主要参与了包括细胞内类固醇激素受体信号通路、RNA聚合酶Ⅱ启动子转录的正调控、胆固醇储存的负调节、RNA聚合酶Ⅱ启动子转录的负调控、细胞内雌激素受体信号通路、甘油三酯稳态、胆固醇生物合成过程、RNA聚合酶Ⅱ启动子的mRNA转录等生物过程,再由KEGG分析,设置P<0.05为筛选条件,得到6条通路,包括化学致癌-受体激活、类固醇激素生物合成、催乳素信号通路、PPAR信号通路、胰岛素抵抗、癌症通路。最后分子对接显示,核心成分与靶点对接得分均<-0.5,说明具有良好的对接活性。结论当归在治疗轻度认知功能障碍的过程中可通过豆甾醇及β-谷甾醇等活性成分发挥作用,涉及到CYP19A1、CYP17A1、ESR1等作用靶点及类固醇激素生物合成、催乳素信号通路、PPAR信号通路、胰岛素抵抗等信号通路。初步明确了当归对MCI具有疗效。
Objective Exploring the key action targets of angelica sinensis for the treatment of mild cognitive dysfunction based on network pharmacology and molecular docking technology.Methods TCMSPW,SwisstaTrgetPrediction,UniProt,and other databases were used to retrieve the active ingredients of angelica sinensis,and the corresponding targets were obtained;the relevant targets of mild cognitive impairment were further retrieved through the databases DisGeNET,GeneCards,and venny2.1.0 platform was used to take the intersection between the targets of angelica sinensis and mild cognitive impairment,and a Venn diagram was constructed.Cytoscape3.9.1 software was used to establish a visual protein interaction network(PPI),GO enrichment analysis and KEGG pathway and gene functional enrichment analysis and network visualization were performed using David database and microson signal website,and finally molecular docking validation was performed by autodock Tools.Results There were 44 common genes of angelica sinensis key genes including NPC1L1,NR1H3,RORC,ESR1,ESR2,SHBG,and 3190 key genes for MCI including APOE,SPG11,PAH,MAPT,SCN8A,APP and so on.After taking the intersection,there were 25 intersection sets between angelica sinensis and MCI related genes,including ESR1,ESR2,SHBG,HMGCR,CYP19A1,AR,CYP17A1 and so on,among which the key targets displayed by PPI were ranked by MCC values,and the top 10 in order were CYP19A1,CYP17A1,ESR1,SHBG,AR,NR3C1,ESR2,HSD11B1,PPARG,PPARA.The GO analysis suggested the involvement of several biological processes,including intracellular steroid hormone receptor signaling pathway,positive regulation of RNA polymeraseⅡpromoter transcription,negative regulation of cholesterol storage,negative regulation of RNA polymerase II promoter transcription,intracellular estrogen receptor signaling pathway,triglyceride homeostasis,cholesterol biosynthetic process,mRNA transcription from RNA polymeraseⅡpromoter,which were further analyzed by KEGG,setting P<0.05 as the screening condition,six pathways were obtained,including chemical carcinogen receptor activation,steroid hormone biosynthesis,prolactin signaling,PPAR signaling,insulin resistance and cancer pathways.Finally,molecular docking showed that the docking scores between core components and targets were all<-0.5,indicating a good docking activity.Conclusion Angelica sinensis in the treatment of mild cognitive dysfunction can act through active ingredients such as stigmasterol andβ-sitosterol,involving targets such as CYP19A1,CYP17A1,and ESR1 and signaling pathways such as steroid hormone biosynthesis,prolactin signaling,PPAR signaling and insulin resistance.It has been preliminarily clarified that angelica sinensis has curative effects on MCI.
作者
张雨梅
朱轶
张明伟
廖礼尚
ZHANG Yu-mei;ZHU Yi;ZHANG Ming-wei(Southwest Medical University,College of Integrated Chinese and Western Medicine,Luzhou 646000,China;不详)
出处
《中国处方药》
2024年第4期1-5,共5页
Journal of China Prescription Drug
基金
四川省科技计划联合创新专项任务(2022YFS0621-B2)
泸州市科技局项目(2022-SYF-36)
关键词
当归
轻度认知功能障碍
网络药理学
分子对接
靶点
通路.
Angelica sinensis
Mild cognitive impairment
Network pharmacology
Molecular docking
Target
Pathways
