目的 基于网络药理学方法探究刺五加总苷抗疲劳的潜在作用机制。方法 以刺五加总苷中7种主要活性成分为研究对象，利用Swiss Target Prediction网络平台预测其作用靶点；通过GeneCards、OMIM、DiGseE数据库获取与疲劳有关的靶标，借助Cytoscape 3.7.2软件构建“活性成分-抗疲劳靶点”网络图，并通过度值筛选核心成分；使用String平台进行蛋白质-蛋白质相互作用（protein-protein interaction，PPI）分析，结合Cytoscape 3.7.2软件构建PPI网络图，通过度值、节点紧密度、节点介度筛选关键靶点，并利用DisGeNET数据库对靶点的类型进行归属；使用AutoDock vina软件对核心成分与关键靶点进行分子对接；采用DAVID数据库对刺五加总苷抗疲劳的作用靶点进行基因本体（gene ontology，GO）富集分析和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。结果 获得刺五加总苷中7种主要活性成分包括刺五加苷A、刺五加苷B、刺五加苷B1、刺五加苷C、刺五加苷D、刺五加苷E和芝麻素，预测得到抗疲劳靶点83个，筛选出核心成分3个，包括刺五加苷B、刺五加苷B1、刺五加苷C，关键靶点4个，包括热休克蛋白90α家族A级成员1（heat shock protein 90 α family class A member 1，HSP90AA1）、信号传导及转录激活因子3（signal transducer and activator of transcription 3，STAT3）、血管内皮生长因子A（vascular endothelial growth factor A，VEGFA）、基质金属蛋白酶9（matrix metalloproteinase 9，MMP9）；分子对接结果显示，核心成分与关键靶点的结合能力与三磷酸腺苷二钠（ATP-2Na）相近；基因富集分析得到GO功能条目250个（P<0.05），通路36条（P<0.05）；网络药理学分析显示，刺五加总苷主要通过药物反应、细胞增殖的正调控、缺氧反应等生物过程，以及调节缺氧诱导因子1（hypoxia-inducible factor 1，HIF-1）、磷脂酰肌醇-3-激酶（phosphoinositide 3-kinase，PI3K）-蛋白激酶B（protein kinase B，Akt）、胰岛素信号通路和物质代谢等发挥抗疲劳作用。结论 初步探究了刺五加总苷抗疲劳作用的潜在靶点和相关通路，为刺五加抗疲劳作用机制的研究提供科学依据和参考。

Objective To explore the anti-fatigue mechanism of Acanthopanax senticosus glycosides based on network pharmacology. Methods Seven main components in A. senticosus glycosides were used as research objects. Swiss Target Prediction was used to predict the potential targets of these components. The related targets of anti-fatigue were provided by GeneCards, OMIM, DiGseE databases, and Cytoscape 3.7.2 software was used to construct the active ingredients-anti-fatigue target network. Core components were selected by degree value. The protein interaction network (PPI) was constructed by String platform and Cytoscape 3.7.2. Key targets were selected by degree value, closeness, and betweenness, and the type of targets were attributed by DisGeNET database. AutoDock vina software was used to dock the molecules of the core components with the key targets. The geneontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways involved in the targets were analyzed by DAVID database. Results A total of seven active components including eleutheroside A, eleutheroside B, eleutheroside B1, eleutheroside C, eleutheroside D, eleutheroside E, sesamin and 83 targets of A. senticosus glycosides were involved, three core components including eleutheroside B, eleutheroside B1 and eleutheroside C, four key targets including heat shock protein 90 α family class A member 1 (HSP90AA1), signal transducer and activator of transcription 3 (STAT3), vascular endothelial growth factor A (VEGFA), and matrix metalloproteinase 9 (MMP9) were screened. Molecular docking showed that the binding ability of the core components to the key targets was close to that of ATP-2Na. After gene enrichment analysis, 250 GO terms (P < 0.05) and 36 KEGG pathways (P < 0.05) were obtained. The results showed that the process of response to drug, positive regulation of cell proliferation, response to hypoxia were mainly involved by adjusting the HIF-1, PI3K-Akt, insulin signaling pathway and material metabolism to exert its anti-fatigue effect. Conclusion Main targets and related pathways of anti-fatigue effects of A. senticosus glycosides were preliminarily investigated, which provided scientific basis and reference for study of anti-fatigue mechanism of A. senticosus.

R285.5

国家自然科学基金资助项目（81973712）；吉林省发改委项目（2020C007）；吉林省科技厅项目（20200602034ZP）