目的 基于“腦-腸軸”理論，通過網(wǎng)絡(luò)藥理學(xué)和分子對接法，分析黃連治療慢性腸炎、失眠、抑郁癥異病同治的作用機(jī)制。方法 利用中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）數(shù)據(jù)庫獲取黃連的活性成分及相關(guān)靶點(diǎn)，檢索GeneCards、OMIM、Drugbank數(shù)據(jù)庫預(yù)測慢性腸炎、失眠、抑郁癥的相關(guān)靶點(diǎn)。通過STRING數(shù)據(jù)庫構(gòu)建交集靶點(diǎn)的蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，通過網(wǎng)絡(luò)拓?fù)鋮?shù)預(yù)測核心靶點(diǎn)，利用Metascape平臺對核心靶點(diǎn)進(jìn)行基因本體（GO）注釋及京都基因與基因組百科全書（KEGG）通路富集分析，最后利用分子對接驗(yàn)證核心成分及核心靶點(diǎn)的結(jié)合能力。結(jié)果 篩選得到黃連活性化合物9種，主要活性成分包括槲皮素、氫化小檗堿、小檗浸堿、黃藤素、小檗堿；活性成分靶點(diǎn)與慢性腸炎、失眠、抑郁癥的交集靶點(diǎn)38個，核心靶點(diǎn)19個，其中IL-6、IL-1β、AKT1、TNF、FOS等靶點(diǎn)度值較高。GO和KEGG分析表明核心靶點(diǎn)主要通過AGE-RAGE、IL-17、TNF等多條信號通路發(fā)揮調(diào)節(jié)作用，核心成分及核心靶點(diǎn)分子對接顯示出良好的結(jié)合活性。結(jié)論 慢性腸炎、失眠、抑郁癥3者雖為不同疾病，但通過“腦-腸軸”互為聯(lián)系。網(wǎng)絡(luò)藥理學(xué)分析顯示黃連通過多組分、多靶點(diǎn)、多通路的藥理作用治療慢性腸炎、失眠及抑郁癥。

Objective Based on "brain-gut axis" theory, the mechanism of Coptidis Rhizoma in treating chronic enteritis, insomnia and depression was analyzed by network pharmacology and molecular docking. Methods The active constituents and related targets of Coptidis Rhizoma were obtained from TCMSP database, and the related targets of chronic enteritis, insomnia and depression were predicted from GeneCards, OMIM and Drugbank databases. The protein interaction network of intersecting targets was built by STRING database, the core targets were predicted by network topological parameters. GO and KEGG analysis were finished by Metascape platform, and the core targets were verified by molecular docking. Results Nine active compounds of Coptidis Rhizoma were obtained, and the main active compounds included quercetin, (R) -canadine, berlambine, palmatine, berberine. There were 38 intersection targets and 19 core targets with chronic enteritis, insomnia and depression, among which IL-6, IL-1β, AKT1, TNF, FOS and other targets had higher degrees. GO and KEGG analysis showed that the core targets played a regulatory role mainly through AGE-RAGE, IL-17, TNF and other signaling pathways, and molecular docking showed the good docking activity. Conclusion Although chronic enteritis, insomnia and depression are different diseases, they are interconnected through the "brain-gut axis". Network pharmacological analysis showed that Coptidis Rhizoma treated chronic enteritis, insomnia and depression through multi-component, multi-target and multi-pathway pharmacological action.

R285.5

國家中醫(yī)藥傳承創(chuàng)新團(tuán)隊(duì)項(xiàng)目（ZYYCXTD-C-202205）；中國中醫(yī)藥循證醫(yī)學(xué)中心業(yè)務(wù)研究室主任專項(xiàng)（2020YJSZX-3）