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

Mechanism of action of Rhizoma Acori graminei-Curcuma aromatic in treatment of Alzheimer’s disease:A study based on network pharmacology

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。

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 Rhizo-ma 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 enrich-ment analysis of core target genes.Cytoscape 3.9.1 and STRING software were used to construct a visualized dis-ease-pathway-target-drug network and a protein-protein interaction network,so as to obtain the gene proteins in-volved in the treatment of AD.Results:The above screening obtained 19 effective constituents,136 potential tar-gets,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 compo-nents,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 mul-tiple genes,targets,and pathways.