目的 采用網(wǎng)絡(luò)藥理學(xué)方法及分子對(duì)接技術(shù)探討柏子養(yǎng)心丸治療失眠癥的潛在分子機(jī)制。方法 通過(guò)TCMSP數(shù)據(jù)庫(kù)收集柏子養(yǎng)心丸的主要化學(xué)成分,經(jīng)ADME篩選活性化合物并獲取其作用靶點(diǎn);搜索GeneCards、OMIM、PharmGKB、TTD、DrugBank數(shù)據(jù)庫(kù)歸并失眠癥相關(guān)疾病基因;使用R語(yǔ)言程序?qū)λ幬锱c疾病靶點(diǎn)取交集并上傳至STRING平臺(tái)構(gòu)建蛋白相互作用(PPI)網(wǎng)絡(luò),應(yīng)用Cytoscape軟件進(jìn)一步判別其核心模塊;基于R語(yǔ)言平臺(tái)對(duì)交集靶點(diǎn)進(jìn)行基因本體(GO)功能與京都基因與基因組百科全書(shū)(KEGG)通路富集分析;利用Cytoscape軟件構(gòu)筑"柏子養(yǎng)心丸活性成分-失眠癥基因"網(wǎng)絡(luò),并使用CytoNCA工具分析其關(guān)鍵藥效組分與核心靶點(diǎn);運(yùn)用AutoDock套件進(jìn)行網(wǎng)絡(luò)關(guān)鍵成分與靶點(diǎn)的分子對(duì)接驗(yàn)證,并追溯PPI核心模塊與其關(guān)聯(lián)成分實(shí)行潛在成分與靶標(biāo)的二次挖掘。結(jié)果 共篩選出槲皮素、山柰酚、木犀草素、黃芩素、柚皮素、β-谷甾醇、豆甾醇、7-O-甲基異微凸劍葉莎醇、7-甲氧基-2-甲基異黃酮等柏子養(yǎng)心丸的有效成分,治療失眠癥的作用靶點(diǎn)為前列腺素內(nèi)過(guò)氧化物合酶2(PTGS2)、雌激素受體1(ESR1)、過(guò)氧化物酶體增殖物激活受體(PPARG)、環(huán)加氧酶1(PTGS1)等,各靶點(diǎn)與對(duì)應(yīng)成分的對(duì)接活性較強(qiáng)。生物學(xué)通路主要涉及神經(jīng)活性配體-受體相互作用通路、神經(jīng)退行性變-多種疾病通路、脂質(zhì)和動(dòng)脈粥樣硬化通路等。結(jié)論 從多角度全方位闡明柏子養(yǎng)心丸以"多成分、多靶點(diǎn)、多途徑"的模式干預(yù)失眠癥的潛在機(jī)制,可為其質(zhì)量標(biāo)準(zhǔn)完善和機(jī)制深入考察夯實(shí)基礎(chǔ)。

Objective To explore the mechanism of Baizi Yangxin Pills in treatment of insomnia based on network pharmacology and molecular docking technology. Methods To collect the primary chemical components of the Baizi Yangxin Pills through the TCMSP database, and screen the target by ADME. GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were searched and utilized to collate insomnia-related disease genes. R language program was applied to take the intersection of drug and disease targets and then uploaded to STRING platform to construct PPI network, and Cytoscape software was adopted to further discriminate its core modules. GO function and KEGG pathway enrichment analysis of intersectional targets were performed based on the R language interface. Cytoscape system was implemented to build up the network of "active components of Baizi Yangxin Pills-insomnia genes", and CytoNCA tool was used to diagnose its key ingredients and core targets. AutoDock suites were adopted to carry out molecular docking validation of network critical components and targets, and the PPI core modules were traced back to their linked ingredients to conduct secondary mining of potential compositions and targets. Results The effective components of the Baizi Yangxin Pills, such as quercetin, kaempferol, luteolin, baicalin, naringenin, β-sitosterol, stigmasterol, 7-O-methylisomucronulatol, 7-methoxy-2-methyl isoflavone were selected. The therapeutic targets of insomnia are PTGS2, ESR1, PPARG, PTGS1, etc. Each target has strong docking activity with the corresponding components. Biological pathways mainly involve neuroactive ligand-receptor interaction pathways, neurodegeneration-multiple disease pathways, lipid and atherosclerotic pathways, etc. Conclusion This study elucidates the potential mechanism of Baizi Yangxin Pills intervention in insomnia with the mode of "multi-component, multi-target and multi-pathway" from multiple perspectives, which can lay a solid foundation for the improvement of its quality standards and in-depth investigation of its mechanism.

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國(guó)家科技重大專(zhuān)項(xiàng)(民口)課題(2018ZX09301-011-003)