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基于网络药理学研究石菖蒲-郁金治疗阿尔兹海默症的作用机制
王 凯,史 欣,柯 珺
0
(宁夏医科大学总医院,宁夏 银川,750004;宁夏医科大学中医学院,宁夏 银川,750004;宁夏医科大学临床医学院,宁夏 银川,750004)
摘要:
目的:基于网络药理学研究石菖蒲-郁金治疗阿尔兹海默症(AD)的作用机制。方法:通过TCMSP数据库筛选石菖蒲、郁金的有效成分,找出其所对应的相关靶点,利用UniProt数据库进行靶点蛋白与基因名的转换,在DisGeNET中寻找AD的基因信息,借助韦恩图找到石菖蒲-郁金与AD相关联的核心靶点基因,利用DAVID数据库对核心靶点基因进行基因本体(GO)功能、京都基因与基因组百科全书(KEGG)通路富集分析。使用Cytoscape 3.9.1、STRING软件构建可视化“疾病-通路-靶点-药物”网络图与蛋白质-蛋白质相互作用(PPI)网络图,得到治疗AD的基因蛋白。结果:筛选获得石菖蒲-郁金有效成分19种,潜在靶点136个,关键靶点基因40个,其中以蛋白激酶1(AKT1)、肿瘤坏死因子-α(TNF-α)、半胱天冬酶3(CASP3)、一氧化氮合酶3(NOS3)、氧化物酶体增殖物激活受体(PPARG)、氧化氢酶(CAT)等靶点作用较为突出。GO功能富集分析显示,GO功能条目主要有血管生成正调节、细胞核、质膜组成成分、序列特异性DNA结合等。KEGG通路富集分析发现,脂质与动脉粥样硬化通路在所有相关条目中关联性最强,对于治疗AD更有意义。结论:石菖蒲-郁金可以从多基因、多靶点、多途径治疗AD。
关键词:  阿尔兹海默症  石菖蒲  郁金  网络药理学  作用机制
DOI:
Mechanism of action of Rhizoma Acori graminei-Curcuma aromatic in treatment of Alzheimer’s disease:A study based on network pharmacology
WANG Kai,SHI Xin,KE Jun
(General Hospital of Ningxia Medical University,Yinchuan 750004,Ningxia,China;College of Traditional Chinese Medicine,Ningxia Medical University,Yinchuan 750004,Ningxia,China;School of Clinical Medicine,Ningxia Medical University,Yinchuan 750004,Ningxia,China)
Abstract:
Objective:To investigate the mechanism of action of Rhizoma Acori graminei-Curcuma aromatic in the treatment of Alzheimer’s disease (AD) based on network pharmacology.Methods:TCMSP database was used to screen for the effective constituents of Rhizoma Acori graminei and Curcuma aromatic and obtain their corresponding targets;UniProt database was used to switch the names of target proteins and genes,and DisGeNET was used to search the gene information of AD;Venn diagram was plotted to obtain the core target genes of Rhizoma Acori graminei-Curcuma aromatic associated with AD;DAVID database was used to perform gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of core target genes.Cytoscape 3.9.1 and STRING software were used to construct a visualized disease-pathway-target-drug network and a protein-protein interaction network,so as to obtain the gene proteins involved in the treatment of AD.Results:The above screening obtained 19 effective constituents,136 potential targets,and 40 key target genes for Rhizoma Acori graminei-Curcuma aromatic,among which AKT1,TNF-α,CASP3,NOS3,PPARG,and CAT had a marked effect.The GO functional enrichment analysis showed that the GO functional terms mainly included positive regulation of angiogenesis,cell nucleus,plasma membrane components,and sequence-specific DNA binding.The KEGG pathway enrichment analysis showed that the lipid and atherosclerosis pathway showed the strongest association among all terms and had a higher value in the treatment of AD.Conclusion:Rhizoma Acori graminei-Curcuma aromatic can exert a therapeutic effect on AD through multiple genes,targets,and pathways.
Key words:  Alzheimer’s disease  Rhizoma Acori graminei  Curcuma aromatic  network pharmacology  mechanism of action

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