目的 基于網(wǎng)絡(luò)藥理學(xué)和分子對接技術(shù)探究南五味子與北五味子治療阿爾茨海默?。ˋD）的作用機制異同。方法 通過中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫及分析平臺（TCMSP）和已發(fā)表的文獻篩選南、北五味子的活性成分，利用Swiss TargetPrediction、OMIM、GeneCards數(shù)據(jù)庫獲得AD相關(guān)疾病靶點，通過Cytoscape 3.9.1繪制“藥物-活性成分-交集靶點”網(wǎng)絡(luò)圖。利用Venny 2.1篩選共性和特有靶點，通過String數(shù)據(jù)庫、Cytoscape 3.9.1構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，利用Cytoscape 3.9.1的CytoNCA工具進行靶點拓?fù)浞治龊Y選關(guān)鍵靶點，Metascape平臺對共性和特有靶點進行基因本體（GO）功能及京都基因與基因組百科全書（KEGG）通路富集分析。利用AutoDock Vina對核心活性成分和關(guān)鍵靶點進行分子對接驗證。結(jié)果 篩選出南五味子活性成分15個，北五味子活性成分13個，二者治療AD共性靶點235個，南五味子治療AD特有靶點137個，北五味子治療AD特有靶點69個。PI3K-Akt信號通路、神經(jīng)活性配體-受體相互作用、鈣信號通路、MAPK信號通路等為南、北五味子治療AD共性信號通路，Th17細胞分化、PPAR信號通路等為南五味子治療AD特有調(diào)控信號通路，cGMP-PKG信號通路、趨化因子信號通路等為北五味子治療AD特有調(diào)控信號通路。分子對接結(jié)果顯示，南五味子核心活性成分五味子醇甲、五味子甲素、五味子酯甲、新南五味子木脂寧、新杜松烷酸B與關(guān)鍵靶點CASP3、ESR1、HIF1A，北五味子核心活性成分五味子醇甲、五味子甲素、五味子酯甲、脫氧三尖杉酯堿、五味子醇乙與關(guān)鍵靶點ADRB2、SLC6A4、ADRBK1均具有較好的結(jié)合活性。結(jié)論 南、北五味子由于產(chǎn)地不同，活性成分及治療AD靶點既有相同也有不同，南、北五味子能通過共有及各自特有靶點發(fā)揮治療AD作用。

Objective To explore the similarities and differences between the mechanism of Schisandra sphenanthera Rehd. et Wils. and Schisandra chinensis (Turcz.) Baill. in treatment of Alzheimer's disease (AD) based on network pharmacology and molecular docking techniques. Methods The active components of S. sphenanthera and S. chinensis were screened from the Traditional Chinese Medicine System Pharmacology Database (TCMSP) and published literature, access to drug and disease targets using the Swiss Target Prediction, OMIM, GeneCards databases, and draw the network diagram of "drug-active component-intersection target" by Cytoscape 3.9.1. Venny 2.1 was used to screen common and unique targets. Protein-protein interaction (PPI) network was constructed by String database and Cytoscape 3.9.1. CytoNCA tool of Cytoscape 3.9.1 was used to screen key targets by target topology analysis. The Metascape platform performs GO functional and KEGG pathway enrichment analysis for common and unique targets. Finally, AutoDock Vina was used to verify the molecular docking of core active components and key targets. Results There were 15 active components of S. sphenanthera, 13 active components of S. chinensis, there are 235 common targets for treating AD, 137 unique targets of S. sphenanthera for treating AD, and 69 unique targets of S. chinensis for treating AD. The PI3KAkt signaling pathway, neuroactive ligand-receptor interaction, calcium signaling pathway and MAPK signaling pathway were common signal pathways of S. sphenanthera and S. chinensis in treating AD. Th17 cell differentiation and PPAR signaling pathway were the unique regulatory signal pathways of S. sphenanthera in treating AD. The cGMP-PKG signaling pathway and chemokine signaling pathway were the unique regulatory signal pathways of S. chinensis in treating AD. Molecular docking results showed that S. sphenanthera core active components schisandrin, schisandrin A, schisantherin A, neokadsuranin and neokadsuranic acid B had good binding activity with key targets CASP3, ESR1 and HIF1A. S. chinensis core active components schisandrin, schisandrin A, schisantherin A, deoxyharringtonine and gomisin A had good binding activity with key targets ADRB2, SLC6A4 and ADRBK1. Conclusion Due to the different origins of S. sphenanthera and S. chinensis, the active components and therapeutic AD targets are both the similarities and differences. S. sphenanthera and S. chinensis can play a role in the treatment of AD through their common and respective unique targets.

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