目的 采用網(wǎng)絡(luò)藥理學(xué)方法探討人參抗阿爾茨海默病的可能靶標(biāo)及作用機(jī)制。方法 利用TCMSP數(shù)據(jù)庫獲取人參活性成分及其所對(duì)應(yīng)的靶標(biāo)。通過GeneCards數(shù)據(jù)庫獲取阿爾茨海默病的治療靶標(biāo)。利用Venn在線工具獲得人參活性成分和阿爾茨海默病的共同作用靶點(diǎn)。運(yùn)用Cytoscape軟件構(gòu)建人參、活性成分、靶標(biāo)間相互作用網(wǎng)絡(luò)關(guān)系圖，并使用CytoHubba插件獲得核心靶點(diǎn)以及核心子網(wǎng)絡(luò)。應(yīng)用DAVID數(shù)據(jù)庫進(jìn)行基因本體（GO）富集分析和京都基因與基因組百科全書（KEGG）通路富集分析。檢索FerrDb數(shù)據(jù)庫，獲得調(diào)控鐵死亡的基因并進(jìn)行分析，最終綜合探析人參活性成分、阿爾茨海默病、鐵死亡3者關(guān)系并作出預(yù)測(cè)。結(jié)果 從人參中篩選出具有作用靶點(diǎn)的16個(gè)有效活性成分，預(yù)測(cè)得到以HMOX1、NOS2、PTGS2、IFNG、MAPK8、JUN和RELA 7個(gè)人參調(diào)控鐵死亡抗阿爾茨海默病的可能作用靶標(biāo)，介導(dǎo)HIF-1、TNF、T細(xì)胞受體、Toll樣受體、神經(jīng)營養(yǎng)因子、cAMP、MAPK、NOD樣受體等信號(hào)通路調(diào)控鐵死亡途徑，從而對(duì)抗阿爾茨海默病的發(fā)生及進(jìn)展。結(jié)論 利用網(wǎng)絡(luò)藥理學(xué)探討了人參抗阿爾茨海默病的多成分、多靶點(diǎn)、多通路的作用特點(diǎn)，并挖掘出人參活性成分調(diào)控鐵死亡抗阿爾茨海默病的可能靶點(diǎn)及信號(hào)轉(zhuǎn)導(dǎo)機(jī)制。

Objective The possible target and mechanism of Ginseng Radix et Rhizoma against Alzheimer's disease were investigated by network pharmacology method. Methods The active ingredients of Ginseng Radix et Rhizoma and their corresponding targets were obtained by using TCMSP database. Therapeutic targets for Alzheimer's disease were obtained from GeneCards database. The co-action targets of Ginseng Radix et Rhizoma active ingredients and Alzheimer's disease were obtained using Venn online tool. Cytoscape software was used to construct the network diagram of interaction between Ginseng Radix et Rhizoma, active ingredient and target, and CytoHubba plug-in was used to obtain the core target and core subnetwork. DAVID database was used for gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. FerrDb database was searched to obtain and analyze the genes regulating ferroptosis. Finally, the data of Ginseng Radix et Rhizoma active ingredients, Alzheimer's disease and ferroptosis were comprehensively analyzed and predicted. Results Sixteen active components were screened from Ginseng Radix et Rhizoma, and seven possible targets of Ginseng Radix et Rhizoma regulating ferroptosis and anti-Alzheimer's disease were predicted, including HMOX1, NOS2, PTGS2, IFNG, MAPK8, JUN, and RELA. Ferroptosis pathway is regulated by mediating HIF-1, TNF, T cell receptor, Toll-like receptor, neurotrophic factor, cAMP, MAPK, NOD-like receptor, and other signaling pathways, thus combating the occurrence and progression of Alzheimer's disease. Conclusion The multi-component, multi-target and multi-pathway action characteristics of Ginseng Radix et Rhizoma against Alzheimer's disease were explored by using network pharmacology, and the possible targets and signal transduction mechanism of Ginseng Radix et Rhizoma active ingredients regulating ferroptosis against Alzheimer's disease were explored.

R285

吉林省自然科學(xué)基金資助項(xiàng)目（20200201515JC）；吉林省教育廳科學(xué)技術(shù)研究項(xiàng)目（JJKH20221091KJ）