目的 基于“脑-肠轴”理论，通过网络药理学和分子对接法，分析黄连治疗慢性肠炎、失眠、抑郁症异病同治的作用机制。方法 利用中药系统药理学数据库与分析平台（TCMSP）数据库获取黄连的活性成分及相关靶点，检索GeneCards、OMIM、Drugbank数据库预测慢性肠炎、失眠、抑郁症的相关靶点。通过STRING数据库构建交集靶点的蛋白质相互作用（PPI）网络，通过网络拓扑参数预测核心靶点，利用Metascape平台对核心靶点进行基因本体（GO）注释及京都基因与基因组百科全书（KEGG）通路富集分析，最后利用分子对接验证核心成分及核心靶点的结合能力。结果 筛选得到黄连活性化合物9种，主要活性成分包括槲皮素、氢化小檗碱、小檗浸碱、黄藤素、小檗碱；活性成分靶点与慢性肠炎、失眠、抑郁症的交集靶点38个，核心靶点19个，其中IL-6、IL-1β、AKT1、TNF、FOS等靶点度值较高。GO和KEGG分析表明核心靶点主要通过AGE-RAGE、IL-17、TNF等多条信号通路发挥调节作用，核心成分及核心靶点分子对接显示出良好的结合活性。结论 慢性肠炎、失眠、抑郁症3者虽为不同疾病，但通过“脑-肠轴”互为联系。网络药理学分析显示黄连通过多组分、多靶点、多通路的药理作用治疗慢性肠炎、失眠及抑郁症。

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

国家中医药传承创新团队项目（ZYYCXTD-C-202205）；中国中医药循证医学中心业务研究室主任专项（2020YJSZX-3）