目的 基于網(wǎng)絡(luò)藥理學(xué)方法探討梔子豉湯治療抑郁、焦慮和失眠的作用機制。方法 篩選梔子豉湯活性成分;通過PharmMapper和CTD獲取成分對應(yīng)的靶點;將成分靶點與TTD、OMIM、DrugBank、CTD、Gene-Cards、DisGeNET數(shù)據(jù)庫中獲取的抑郁、焦慮和失眠疾病靶點分別取交集,將交集靶點分別導(dǎo)入String在線網(wǎng)站構(gòu)建蛋白質(zhì)相互作用網(wǎng)絡(luò),運用Cytoscape軟件進(jìn)行可視化分析,根據(jù)度值篩選出關(guān)鍵靶點;通過Matescape數(shù)據(jù)庫對交集靶點進(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;利用Cytoscape軟件構(gòu)建"成分-靶點-通路"網(wǎng)絡(luò),根據(jù)度值等篩選出核心活性成分。結(jié)果 共篩選19個活性成分,核心活性成分有大豆苷元、染料木素、梔子苷、蘆丁、綠原酸等;活性成分和抑郁、焦慮和失眠疾病交集靶點分別為77、91、111個;KEGG通路富集分析結(jié)果顯示,梔子豉湯治療抑郁、焦慮和失眠主要涉及雌激素、絲裂原活化蛋白激酶、磷酸肌醇-3-激酶-蛋白激酶B(PI3K-Akt)、叉頭狀轉(zhuǎn)錄因子(FOXO)、神經(jīng)活性配體-受體相互作用、白細(xì)胞介素-17(IL-17)、多巴胺突觸、糖尿病并發(fā)癥中的晚期糖基化終產(chǎn)物及其受體(AGE-RAGE)等信號通路。結(jié)論 梔子豉湯可通過多成分、多靶點和多通路發(fā)揮治療抑郁、焦慮和失眠的作用,為深入研究梔子豉湯的藥效物質(zhì)基礎(chǔ)和藥理作用提供理論依據(jù)。

Objective To explore the mechanism of Zhizichi Decoction in treatment of depression, anxiety and insomnia based on network pharmacology.Methods The main active ingredients of Zhizichi Decoction were screened. The target points corresponding to the components were obtained through PharmMapper and CTD. Intersection of component targets and depression, anxiety, and insomnia disease targets were obtained in TTD, OMIM, DrugBank, CTD, Gene-Cards, and DisGeNET databases, respectively. The intersection targets were imported into the String online website to construct a protein interaction network, and Cytoscape software was used for visual analysis, and the key targets were screened out according to the degree value. GO biological analysis and KEGG pathway enrichment analysis of the intersection target through the Matescape database. Cytoscape was used to construct a “componenttarget-pathway” network, and the core active ingredients were screened out according to the degree value.Results A total of 19 active ingredients were screened. The core active ingredients were daidzein, genistein, geniposide, rutin, isochlorogenic acid A, etc. The intersection of depression, anxiety, and insomnia components and disease targets respectively were 77, 91, and 111. KEGG pathway enrichment analysis results showed that the treatment of depression, anxiety, and insomnia by Zhizichi Decoction mainly involved estrogen, mitogen-activated protein kinase, PI3K-Akt, FOXO, neuroactive ligand-receptor interaction, IL-17, dopamine synapses, AGE-RAGE and other signaling pathways in diabetic complications.Conclusion Zhizichi Decoction plays a role in treatment of depression, anxiety and insomnia through multi-component, multi-target and multi-channel, which provides a theory for in-depth study of the pharmacological basis and pharmacological effects of Zhizichi Decoction.

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國家中藥材產(chǎn)業(yè)技術(shù)體系專項(CARS-21);國家中醫(yī)藥管理局全國中藥資源普查項目(GZY-KJS-2018-004);2018年中醫(yī)藥公共衛(wèi)生服務(wù)補助專項“全國中藥資源普查項目”(財社[2018]43號)