小建中汤治疗抑郁症作用机制的网络药理学研究

Mechanism of Xiaojianzhong Decoction in the Treatment of Depression Based on Network Pharmacology

目的基于网络药理学探讨小建中汤治疗抑郁症多靶点、多通路的作用机制。方法采用计算机检索TCMSP,PubChem,Swiss TargetPrediction数据库,筛选小建中汤治疗抑郁症的潜在活性成分及作用靶点,运用Cytoscape 3.8.0软件构建潜在活性成分-靶点网络;检索GeneCard,OMIM,DisGeNET数据库,获取与抑郁症相关的靶点,通过Uniport数据库校对靶点基因名;运用String数据库确定核心靶点;使用Metascape在线分析工具,并通过GO富集分析和KEGG通路分析构建蛋白互作网络。结果从小建中汤中筛选出68个活性成分,包括荷叶碱、可可碱、左旋千金藤啶碱等;共得到144个与抑郁症相关的重合靶点,根据网络节点自由度筛选出核心作用靶点基因36个,包括雌激素受体1、丝氨酸/苏氨酸蛋白激酶1、乙酰胆碱酯酶、单胺氧化酶B等;通过生物过程GO富集分析获得信号通路630条,包括化学突触传递、G蛋白耦联受体信号通路、与环状核苷酸第二信使耦联等;通过KEGG通路分析获得核心靶点的相关通路31条,包括神经活性配体-受体相互作用、血清素能突触、钙信号、多巴胺能突触、环磷酸腺苷(cAMP)等通路。结论小建中汤治疗抑郁症具有多靶点、多途径、多通路的特点,可能通过神经活性配体-受体相互作用、血清素能突触、钙信号、多巴胺能突触、cAMP等通路发挥抗抑郁作用。

Objective To investigate the mechanism of multiple targets and multiple pathways of Xiaojianzhong Decoction in the treatment of depression based on network pharmacology.Methods The databases of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),PubChem and Swiss TargetPrediction were searched to screen the potential active ingredients and targets of Xiaojianzhong Decoction in the treatment of depression.The potential active ingredient-target network was constructed through Cytoscape 3.8.0 software.The targets related to depression were obtained by searching GeneCard,OMIM and DisGeNET databases,and the target gene names were proofread through the Uniport database.The core target was determined through the string database.The protein-protein interaction(PPI)network was constructed by the Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis through the Metascape online analysis tool.Results A total of 68 active ingredients were screened from Xiaojianzhong Decoction,including nuciferine,theobromine,L-stepholidine,etc.A total of 144 coincident targets related to depression were obtained,and 36 core target genes were screened according to the freedom degree of network nodes,including estrogen receptor 1,serine/threonine-protein kinase 1,acetylcholinesterase,monoamine oxidase B,etc.A total of 630 signal pathways were obtained by GO enrichment analysis for biological process,including chemical synaptic transmission,G protein coupled-receptor signal pathway,coupling with cyclic nucleotide second messenger,etc.A total of 31 related pathways of core targets were obtained by KEGG pathway analysis,including neuroactive ligand-receptor interaction,serotonergic synapse,calcium signal,dopaminergic synapse,cyclic adenosine monophosphate(cAMP),etc.Conclusion Xiaojianzhong Decoction has the characteristics of multiple targets,multiple channels and multiple pathways in the treatment of depression.It may play an antidepressant role through neuroactive ligand-receptor interaction,serotonergic synapse,calcium signal,dopaminergic synapse and cAMP pathways.