目的 基于网络药理学探讨及比较金钗石斛Dendrobium nobile Lindl.和霍山石斛D. huoshanense活性成分治疗阿尔茨海默病的作用机制。方法 基于中国知网、万方和PubMed数据库收集金钗石斛、霍山石斛的有效成分;PubChem平台查询活性成分结构;SwissADME平台筛选金钗石斛、霍山石斛活性成分的靶点;SwissTartgetPrediction平台预测各活性成分的作用靶点;GeneCards和OMIM数据库检索阿尔茨海默病相关靶点;Cytoscape 3.9.1构建"活性成分-疾病-靶点"网络图;String数据库分析并构建药物与疾病的蛋白质相互作用(PPI)网络;利用Metascape进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析。结果 共获得金钗石斛有效成分84个,核心成分为crepidatin、N-isopentenyl-6-hydroxydendroxinium、3-O-methylgigantol等;霍山石斛有效成分56个,核心成分为erianin、dendrocrepine、dendrocandin U等;金钗石斛和霍山石斛映射疾病靶点分别为255、243个,共同靶点208个,核心靶点为蛋白激酶B(Akt)、甘油醛-3-磷酸脱氢酶(GAPDH)、白蛋白(ALB)等;GO功能和KEGG富集分析结果显示,金钗石斛、霍山石斛治疗阿尔茨海默病的共同作用部位主要在树突;主要通路为磷脂酰肌醇-3-羟激酶(PI3K)-Akt信号通路、神经退行性变的途径-多种疾病、阿尔茨海默病通路等。此外,金钗石斛可作用于神经元细胞体,调节Toll样受体信号通路;霍山石斛可作用于轴突,调节丝裂原活化蛋白激酶(MAPK)信号通路。结论 金钗石斛与霍山石斛都可能通过不同成分和不同通路治疗阿尔茨海默病。

Objective To explore and compare the differences in the mechanism of action between the Dendrobium nobile and Dendrobium huoshanense in treatment of Alzheimer's disease. Methods The components of Dendrobium nobile and Dendrobium huoshanense were searched from literature of CNKI, WanFang, and PubMed database. The active components structure were searched by PubChem. SwissADME platform screen the active ingredient target of Dendrobium nobile and Dendrobium huoshanense. Both targets were predicted by SwissTargetPrediction database. Targets associated with Alzheimer's disease were retrieved in both Genecards and OMIM databases. The "active component-disease-target" network was constructed by Cytoscape 3.9.1 software. PPI network between drugs and diseases was constructed by String database. GO and KEGG results were performed by Metascape. Results The results showed Dendrobium nobile were 84 effective components, for example crepidatin, N-isopentenyl-6-hydroxydendroxinium, and 3-O-methylgigantol so on, and 255 targets. Dendrobium huoshanense were 56 effective components, for example erianin, crepidamine, and dendrocandin U so on, and 243 targets. Their common targets have 208, such as Akt1, GAPDH, and ALB. The results of GO and KEGG showed that the common site of action of Alzheimer's is dendrites, and the main signaling pathway is PI3K-Akt signaling pathway, pathway of neurodegeneration-multiple diseases, and Alzheimer disease. And Dendrobium nobile the site of action of Alzheimer's is neuronal cell body, and the main the main signaling pathway is Toll-like receptor signaling pathway. And Dendrobium huoshanense the site of action of Alzheimer's is axon, and the main the main signaling pathway is MAPK signaling pathway. Conclusion They may act in Alzheimer's through different components and different pathways.

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国家自然科学基金资助项目(81673860)；广州医科大学科研能力提升计划项目(广医发[2023]16号)