| 摘要: |
| 目的：基于网络药理学及分子对接探讨杜仲多糖(eucommia ulmoides polysaccharides，EUP)改善高原低氧骨骼肌肌肉力量下降(high altitude hypoxic-skeletal muscle strength decrease，HAH-SMSD)的潜在作用机制。方法：通过查阅文献、中药系统药理数据库、本草组鉴和Swiss Target Prediction数据库获得EUP化学成分信息并预测其作用靶点。通过人类基因数据库和在线人类孟德尔遗传数据库检索HAH-SMSD的相关靶点。在微生信平台中利用Venny图筛选二者交集靶点。运用Cytoscape 3.9.1软件构建EUP-化学成分-靶点的网络拓扑结构图。使用蛋白质相互作用数据库和Cytoscape 3.9.1软件进行蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络分析，根据度值筛选出核心靶点。结合基因注释与分析资源数据库、Cytoscape 3.9.1软件对交集靶点进行基因本体和京都基因与基因组百科全书富集分析，构建化学成分-疾病-靶点通路网络图，根据度值筛选出关键成分。最后，利用PyMOL 2.6.0、Open Babel 2.4.1、AutoDock 4.2.6软件进行分子对接。结果：EUP含有11种单糖成分。其中，葡萄糖（glucose，Glc）、葡萄糖醛酸（glucuronic acid，GlcA）等7种单糖可能为其关键成分。EUP与HAH-SMSD有63个交集靶点。其中，甘油醛-3-磷酸脱氢酶、肿瘤坏死因子、过氧化物酶体增殖物激活受体γ、基质金属蛋白酶9等10个靶点可能是EUP改善HAH-SMSD的核心靶点，其可能参与癌症信号通路、脂质与动脉粥样硬化、糖尿病并发症中的AGE-RAGE（advanced glycation end products/receptor for advanced glycation end products，AGE/RAGE）通路、低氧诱导因子-1α （hypoxia-inducible factor 1 alpha，HIF-1α）信号通路、磷脂酰肌醇3激酶/蛋白激酶B （phosphatidylinositol 3-kinase /protein kinase B，PI3K-Akt）信号通路、过氧化物酶体增殖物激活受体（peroxisome proliferators-activated receptor，PPAR）信号通路等关键通路。分子对接发现，EUP关键活性成分与核心靶点结合能均小于-3 kcal/mol，具有良好的亲和力。结论：EUP含有的Glc、GlcA等关键活性成分，通过多靶点、多途径等方式改善HAH-SMSD，其可能通过HIF-1α、PI3K-AKT、PPAR等关键信号通路发挥改善HAH-SMSD的作用。 |
| 关键词: 杜仲多糖 高原 低氧 骨骼肌肌肉力量 网络药理学 分子对接 |
| DOI： |
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| Mechanism of action of Eucommia ulmoides polysaccharides in improving the reduction in skeletal muscle strength in plateau hypoxic environment: A study based on network pharmacology and molecular docking |
| GAO Yutong,LI Xiaoyi,TAO Mengdi |
| (Tianjin University of Traditional Chinese Medicine，Tianjin 301617，China;The Academy of Military Medical Sciences of the People’s Liberation Army Academy of Military Sciences，Tianjin 300050，China) |
| Abstract: |
| Objective：To investigate the potential mechanism of action of Eucommia ulmoides polysaccharides (EUP) in improving high altitude hypoxic-skeletal muscle strength decrease (HAH-SMSD) based on network pharmacology and molecular docking.Methods: Related articles，Traditional Chinese Medicine Systems Pharmacology Database，HERB database，and Swiss Target Prediction database were searched to obtain the chemical components of EUP and predict their action targets，and Human Genome Database and the Online Mendelian Inheritance in Man database were used to obtain the targets associated with HAH-SMSD.The Venny diagram in Weishengxin platform was used to obtain the intersecting targets of the above two groups of targets.Cytoscape 3.9.1 was used to establish a EUP-chemical component-target topology network.The protein interaction databases and Cytoscape 3.9.1 were used to perform protein-protein interaction (PPI) network analysis，and core targets were obtained based on degree values.The Gene Ontology Annotation & Analysis Resources Database and Cytoscape 3.9.1 were used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the intersecting genes;a chemical component-disease-target network was established，and key components were obtained based on degree values.PyMOL 2.6.0，Open Babel 2.4.1，and AutoDock 4.2.6 were used for molecular docking.Results: There were 11 monosaccharide components in EUP，among which 7 monosaccharides，including glucose (Glc) and glucuronic acid (GlcA)，might be the key components.There were 63 intersecting targets between EUP and HAH-SMSD，among which 10 targets (including glyceraldehyde-3-phosphate dehydrogenase，tumor necrosis factor，peroxisome proliferator-activated receptor γ，and matrix metalloproteinase-9) might be the core targets of EUP in improving HAH-SMSD，and they might be involved in the key pathways such as the cancer signaling pathway，the lipid and atherosclerosis pathway，the advanced glycation end products/receptor for advanced glycation end products pathway，the hypoxia-inducible factor 1α (HIF-1α) signaling pathway，the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway，and the peroxisome proliferator-activated receptor (PPAR) signaling pathway.Molecular docking showed that the key active components of EUP had a binding energy of <-3 kcal/mol to the core targets，showing good affinity.Conclusion: EUP has the key active components of Glc and GlcA and improves HAH-SMSD through multiple targets and pathways，possibly by regulating the key pathways such as the HIF-1α，PI3K-AKT，and PPAR signaling pathways. |
| Key words: Eucommia ulmoides polysaccharides high altitude hypoxic environment skeletal muscle strength network pharmacology molecular docking |
