目的 通過超高效液相色譜-靜電場(chǎng)軌道阱高分辨質(zhì)譜（UPLC-Q-Exactive-Focus-MS/MS）分析酸棗仁中的化學(xué)成分，依據(jù)解析的化學(xué)成分及中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺(tái)（TCMSP）、本草組鑒數(shù)據(jù)庫（HERB）獲取的酸棗仁主要成分結(jié)合網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接技術(shù)初步預(yù)測(cè)其抗阿爾茨海默?。ˋD）的藥效物質(zhì)基礎(chǔ)，篩選出潛在功效成分，預(yù)測(cè)作用機(jī)制。方法 采用UPLC-Q-Exactive Focus-MS/MS對(duì)酸棗仁進(jìn)行化學(xué)成分分析，分別在正、負(fù)離子模式下掃描，結(jié)合對(duì)照品、文獻(xiàn)中的碎片離子信息、保留時(shí)間進(jìn)行匹配，確認(rèn)化學(xué)成分。利用TCMSP、HERB數(shù)據(jù)庫獲取酸棗仁的主要成分及其對(duì)應(yīng)作用靶點(diǎn)信息；通過GeneCards、OMIM數(shù)據(jù)庫獲得AD相關(guān)疾病靶點(diǎn)；將酸棗仁主要成分對(duì)應(yīng)靶點(diǎn)與AD靶點(diǎn)取交集，借助String 11.5平臺(tái)和Cytoscape 3.7.2軟件繪制交集基因蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)；利用DAVID 6.8對(duì)核心靶點(diǎn)進(jìn)行基因本體（GO）功能與京都基因與基因組百科全書（KEGG）通路富集分析，通過微生信云平臺(tái)對(duì)富集結(jié)果可視化；借助AutoDock Tools軟件對(duì)核心成分及關(guān)鍵靶點(diǎn)基因進(jìn)行分子對(duì)接。結(jié)果 酸棗仁定性分析中共鑒定出40個(gè)化合物，主要包括3個(gè)有機(jī)酸類、28個(gè)黃酮類、8個(gè)生物堿類、1個(gè)皂苷類；篩選出發(fā)揮改善AD作用的核心成分5個(gè)，包括擬雌內(nèi)酯、油酸、山柰酚、烏藥堿、酸李堿；酸棗仁改善AD的核心靶點(diǎn)有JUN、AKT1、STAT3、MAPK14、ESR1、IL16等；KEGG通路分析共得到157條通路，其中PI3K-Akt信號(hào)通路、MAPK信號(hào)通路、HIF-1信號(hào)通路排名靠前；GO富集分析得到生物過程（BP）條目336個(gè)、細(xì)胞組分（CC）條目45個(gè)、分子功能（MF）42個(gè)。分子對(duì)接結(jié)果顯示，酸棗仁的4個(gè)核心成分與關(guān)鍵靶點(diǎn)間存在分子結(jié)合位點(diǎn)且結(jié)合能較強(qiáng)，均小于-20.93 kJ·mol^-1。結(jié)論 通過UPLC-Q-Exactive-Focus-MS/MS解析的化學(xué)成分結(jié)合網(wǎng)絡(luò)藥理學(xué)、分子對(duì)接預(yù)測(cè)了酸棗仁是通過多成分、多靶點(diǎn)、多途徑來發(fā)揮抗AD作用的。

Objective To analyze the chemical components of Ziziphi Spinosae Semen (ZSS) by UPLC-Q-Exactive-Focus-MS/MS, then predict the pharmacodynamic substance basis of treating Alzheimer's disease (AD) based on its chemical components, its main active components obtained from TCMSP and HERB database, network pharmacology and molecular docking technology, checking out the potential efficacy ingredients and mechanism of action. Methods UPLC-Q-Exactive-Focus-MS/MS was used to analyze the chemical components of ZSS, which were scanned in positive and negative modes respectively. The chemical components was confirmed by matching the reference substance with the fragment ion information and retention time. The active ingredients and action targets of ZSS were obtained through TCMSP databases and HERB databases, AD targets were obtained from GeneCards and OMIM databases. The corresponding targets of the main ingredients of ZSS were intersected with the AD targets, and the protein-protein interaction (PPI) network of the intersected genes was mapped with the help of STRING 11.5 platform and Cytoscape 3.7.2 software. The analysis of gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed by the DVIAD 6.8 online database and visually presented through the platform of bioinformatics. Furthermore, molecular docking technology was performed to validate the binding pattern and affinity between the key ingredients and the crucial targets by using AutoDock Tools software. Results There were 40 chemical components analyzed by qualitative analysis of ZSS, including three organic acids, 28 flavonoids, eight alkaloids, one saponin. Screening out five core components that play a therapeutic role in AD, including coumestrol, oleic acid, kaempferol, coclaurine and zizyphusine, etc. The core targets of ZSS for treating AD include JUN, AKT1, STAT3, MAPK14, ESR1, IL16, etc. A total of 157 pathways were identified through KEGG pathway analysis, with PISKAkt, MAPK and HIF-1 response related signaling pathways ranking high. GO enrichment analysis yielded 336 entries for biological processes (BP), 45 entries for cellular components (CC), and 42 entries for molecular functions (MF). The molecular docking results showed that the binding energy between the key biotargets and the four potential active components were much less than -20.93 kJ·mol-1. Conclusion Based on the chemical components analyzed by UPLC-Q-Exactive-Focus-MS/MS combined with network pharmacology, molecular dock, ZSS plays a role in anti-Alzheimer's disease through multi-components, multi-targets, and multi-pathways.

R284.1；R285.5

陜西省中醫(yī)藥管理局中醫(yī)藥全省性?？顚ｍ?xiàng)項(xiàng)目（2021-QYZL-01）；陜西省重點(diǎn)研發(fā)計(jì)劃一般項(xiàng)目（2022-SF-315）；“陜西省中醫(yī)藥管理局雙鏈融合”中青年科研創(chuàng)新團(tuán)隊(duì)（2022-SLRH-YQ-003）；陜西省中醫(yī)藥管理局“醫(yī)研校企”中醫(yī)藥傳承創(chuàng)新平臺(tái)（中醫(yī)藥創(chuàng)新藥物/器械“研發(fā)-轉(zhuǎn)化-推廣”平臺(tái)）；陜西省中醫(yī)藥研究院“苗圃計(jì)劃”一般項(xiàng)目（2021-26）