目的 基于網(wǎng)絡(luò)藥理學(xué)探討及比較金釵石斛Dendrobium nobile Lindl.和霍山石斛D. huoshanense活性成分治療阿爾茨海默病的作用機(jī)制。方法 基于中國知網(wǎng)、萬方和PubMed數(shù)據(jù)庫收集金釵石斛、霍山石斛的有效成分;PubChem平臺查詢活性成分結(jié)構(gòu);SwissADME平臺篩選金釵石斛、霍山石斛活性成分的靶點(diǎn);SwissTartgetPrediction平臺預(yù)測各活性成分的作用靶點(diǎn);GeneCards和OMIM數(shù)據(jù)庫檢索阿爾茨海默病相關(guān)靶點(diǎn);Cytoscape 3.9.1構(gòu)建"活性成分-疾病-靶點(diǎn)"網(wǎng)絡(luò)圖;String數(shù)據(jù)庫分析并構(gòu)建藥物與疾病的蛋白質(zhì)相互作用(PPI)網(wǎng)絡(luò);利用Metascape進(jìn)行基因本體(GO)功能及京都基因與基因組百科全書(KEGG)通路富集分析。結(jié)果 共獲得金釵石斛有效成分84個(gè),核心成分為crepidatin、N-isopentenyl-6-hydroxydendroxinium、3-O-methylgigantol等;霍山石斛有效成分56個(gè),核心成分為erianin、dendrocrepine、dendrocandin U等;金釵石斛和霍山石斛映射疾病靶點(diǎn)分別為255、243個(gè),共同靶點(diǎn)208個(gè),核心靶點(diǎn)為蛋白激酶B(Akt)、甘油醛-3-磷酸脫氫酶(GAPDH)、白蛋白(ALB)等;GO功能和KEGG富集分析結(jié)果顯示,金釵石斛、霍山石斛治療阿爾茨海默病的共同作用部位主要在樹突;主要通路為磷脂酰肌醇-3-羥激酶(PI3K)-Akt信號通路、神經(jīng)退行性變的途徑-多種疾病、阿爾茨海默病通路等。此外,金釵石斛可作用于神經(jīng)元細(xì)胞體,調(diào)節(jié)Toll樣受體信號通路;霍山石斛可作用于軸突,調(diào)節(jié)絲裂原活化蛋白激酶(MAPK)信號通路。結(jié)論 金釵石斛與霍山石斛都可能通過不同成分和不同通路治療阿爾茨海默病。

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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國家自然科學(xué)基金資助項(xiàng)目(81673860)；廣州醫(yī)科大學(xué)科研能力提升計(jì)劃項(xiàng)目(廣醫(yī)發(fā)[2023]16號)