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张卓,时晶,魏明清,李婷,侯敏哲,徐江林.基于网络药理学及分子对接探讨熟地黄-山茱萸药对治疗阿尔茨海默病的潜在机制[J].湖南中医药大学学报英文版,2022,42(7):1139-1151.[Click to copy
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| 基于网络药理学及分子对接探讨熟地黄-山茱萸药对治疗阿尔茨海默病的潜在机制 |
| 张卓,时晶,魏明清,李婷,侯敏哲,徐江林 |
| (北京中医药大学东直门医院, 北京 100029) |
| 摘要: |
| 目的 采用网络药理学及分子对接技术探讨熟地黄-山茱萸药对治疗阿尔茨海默病（Alzheimer’s disease,AD）的活性成分和潜在分子机制。方法 通过TCMSP数据库、SwissTargetPrediction平台、GeneCards和DisGeNET数据库及查阅文献收集并获取熟地黄和山茱萸的主要化学成分、作用靶点及AD疾病的相关靶点。将疾病靶点与药物靶点取交集获得熟地黄-山茱萸药对治疗AD的潜在靶点，将这些交集靶点导入STRING数据库，建立蛋白质-蛋白质相互作用（protein-protein interaction,PPI）网络。利用Cytoscape软件对PPI网络进行拓扑分析并提取核心靶点，利用CytoNCA插件计算度值，筛选出药对的关键成分。通过Metascape平台进行GO和KEGG通路富集分析，并构建“中药-相关关键成分-关键靶点-通路”网络，然后使用AutoDock Vina和PyMOL软件对核心靶点和关键成分进行分子对接。结果 筛选出熟地黄-山茱萸药对治疗AD的10个关键成分、718个药物靶点和450个疾病靶点，药物与疾病的共同靶点120个。PPI网络最终筛选确定了7个关键核心靶点。GO生物过程分析发现关键核心靶点主要富集于Notch受体加工、生物碱代谢过程以及多巴胺分解代谢过程等。KEGG富集分析得到10条作用通路。在分子对接中，各核心靶点与各关键成分表现出较强的结合活性。结论 熟地黄-山茱萸药对可能依靠墙草碱、四氢鸭脚木碱和亚油酸乙酯等关键核心成分，通过对苏氨酸激酶1（AKT1）、丝裂原活化蛋白激酶3（MAPK3）、肿瘤蛋白P53（TP53）和肿瘤坏死因子（TNF）等靶点的调节，参与多个相关信号通路，发挥抑制神经元凋亡、抗炎、增强突触可塑性等神经元保护作用以治疗AD。 |
| 关键词: 阿尔茨海默病 熟地黄 山茱萸 网络药理学 分子对接 作用机制 |
| DOI：10.3969/j.issn.1674-070X.2022.07.013 |
| Received:November 03, 2021 |
| 基金项目:国家自然科学基金项目（82074362）；中央高校基本科研业务费专项资金项目(2019-JYB-TD-007)；国家重点研发计划项目（2018YFC1704100）；中医药传承与创新“百千万”人才工程（岐黄工程）岐黄学者。 |
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| Potential mechanism of Shudihuang (Rehmanniae Radix Praeparata)-Shanzhuyu (Corni Fructus) in the treatment of Alzheimer's disease based on network pharmacology and molecular docking |
| ZHANG Zhuo,SHI Jing,WEI Mingqing,LI Ting,HOU Minzhe,XU Jianglin |
| (Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100029, China) |
| Abstract: |
| Objective To explore the active components and potential molecular mechanism of Shudihuang (Rehmanniae Radix Praeparata)-Shanzhuyu (Corni Fructus) in the treatment of Alzheimer's disease (AD). Methods The main chemical components, action targets and related targets of AD of Shudihuang (Rehmanniae Radix Praeparata)-Shanzhuyu (Corni Fructus) were collected through TCMSP database, SwissTargetPrediction platform, GeneCards, DisGeNET database and literature review. The potential targets of Shudihuang (Rehmanniae Radix Praeparata)-Shanzhuyu (Corni Fructus) for the treatment of AD were obtained by intersection of disease targets and drug targets. Intersection targets were imported into STRING database to establish protein-protein interaction (PPI) network. The topology of PPI network was analyzed by Cytoscape software, and the CytoNCA plug-in was used to calculate the degree value and screen out the key components of drug pairs. GO and KEGG pathways were enriched and analyzed through Metascape platform, and the "herb-compound-target-pathway" network was constructed. Autodock Vina and PyMol software were used for molecular docking of hub targets and key components. Results A total of 10 key components, 718 drug targets, 450 disease targets, and 120 common targets of Shudihuang (Rehmanniae Radix Praeparata)-Shanzhuyu (Corni Fructus) for treating AD were screened out. PPI network finally screened and identified 7 key core targets. GO biological process analysis found that the hub targets were mainly concentrated in Notch receptor processing, alkaloid metabolic process and dopamine catabolic process. KEGG enrichment analysis showed 10 pathways. In molecular docking, the hub targets and key components showed strong binding activity. Conclusion Shudihuang (Rehmanniae Radix Praeparata)-Shanzhuyu (Corni Fructus) may regulate multiple related signaling pathways through some key components such as n-isobutyldeca-trans-2-trans-4-dienamide, tetrahydroalstonine and mandenol, with the regulation of threonine kinase 1 (AKT1), mitogen-activated protein kinase 3 (MAPK3), tumor protein P53 (TP53) and tumor necrosis factor (TNF). It is involved in multiple related signaling pathways and plays a protective role in the treatment of AD, such as inhibiting neuronal apoptosis, anti-inflammatory and enhancing synaptic plasticity. |
| Key words: Alzheimer's disease Shudihuang (Rehmanniae Radix Praeparata) Shanzhuyu (Corni Fructus) network pharmacology molecular docking mechanism |
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