基于网络药理学的苓桂术甘汤治疗阿尔茨海默病的潜在作用机制研究

Potential mechanism of Linggui Zhugan Decoction for treatment of Alzheimer’s disease based on network pharmacology

目的利用网络药理学技术研究苓桂术甘汤治疗阿尔茨海默病(AD)的潜在作用机制。方法利用中药系统药理学分析平台(TCMSP)、Swiss、SuperPred和Stitch数据库寻找与苓桂术甘汤中4味中药相关的化学成分及其作用靶点,并以口服利用度(OB)≥30%、类药性(DL)≥0.18为阈值对化合物进行筛选,再通过文献查找加以补充;通过OMIM、TTD、GAD、Pharm Gkb数据库获取与AD疾病相关的靶标,并进一步筛选得到苓桂术甘汤治疗AD的潜在作用靶点;采用DAVID6.8数据库对相关潜在作用靶点进行GO分析及KEGG代谢通路富集分析;利用Cytoscape软件构建“单味药-活性成分-作用靶点”相互作用网络并进行度值和中介度分析,确认可能的关键靶点和关键通路。结果在苓桂术甘汤中,共筛选出126个与AD相关的潜在活性成分和120个潜在作用靶点;GO生物功能分析共包含565条富集结果,其中生物过程396条,分子功能121条,细胞组成48条,主要涉及蛋白结合、细胞、氧化还原过程等;KEGG富集得到67条代谢通路,主要包括神经活性配体-受体相互作用通路、癌症通路、5-羟色胺能突触通路和钙信号通路等。结论网络药理学研究结果揭示了苓桂术甘汤治疗AD的多成分、多靶点、多途径的作用特点,并预测了其可能的活性成分、作用通路和关键靶点,为其药效物质基础和作用机制研究提供了理论基础。

Objective To study the potential mechanism of Linggui Zhugan Decoction in the treatment of Alzheimer's disease(AD)by using network pharmacological technology.Methods Firstly,TCMSP,Swiss,SuperPred,Stitch databases and supplement literatures were combined to search for the chemical compounds and the potential targets related to the four herbs in Linggui Zhugan Decoction,using the oral bioavailability(OB)≥30%,drug-like(DL)≥0.18 as screening conditions.Meanwhile,the targets related to AD were screened through OMIM,TTD,GAD and Pharm Gkb databases.Moreover,the interactive targets of Linggui Zhugan Decoction and AD were further acquired.Then,Gene Ontology(GO)analysis and KEGG metabolic pathway enrichment analysis of interactive targets were performed using DAVID 6.8 database.Finally,degree and betweenness centrality analysis were performed to find potential key targets and key pathways after the"Herbs-Active Compounds-Targets"interaction network was constructed by Cytoscape software.Results There were 126 potential active compounds and 120 potential interactive targets in Linggui Zhugan Decoction.A total of 565 enrichment results were obtained by GO analysis,including 396 biological processes,121 molecular functions and 48 cell components,mainly involving protein binding,cell,oxidation-reduction process,etc.Simultaneously,the selected targets were enriched by KEGG analysis and it indicated that 67 metabolic pathways play an important role in AD,primarily including neuroactive ligand-receptor interaction,pathways in cancer,serotonergic synapse and calcium signaling pathway,etc.Conclusion The synergetic effect of Linggui Zhugan Decoction with multi-compounds,multi-targets and multi-pathways in the treatment of AD were revealed by network pharmacology,which provides a theoretical basis for the study of its pharmacodynamic material basis and action mechanism.