国际医药卫生导报 ›› 2025, Vol. 31 ›› Issue (16): 2693-2698.DOI: 10.3760/cma.j.cn441417-20241125-16011

• 论著 • 上一篇    下一篇

基于网络药理学研究小檗碱治疗结肠炎的机制

薛雪峰1  刘文栋1  王捷虹2   

  1. 1西安中医脑病医院重症医学科,西安 710038;2陕西中医药大学附属医院消化一科,咸阳 712000

  • 收稿日期:2024-11-25 出版日期:2025-08-15 发布日期:2025-08-28
  • 通讯作者: 刘文栋,Email:523260239@qq.com
  • 基金资助:

    陕西省中医药管理局重点研究室项目(陕中医药发【2018】32号)

Mechanism of berberine in treating colitis based on network pharmacology

Xue Xuefeng1, Liu Wendong1, Wang Jiehong2   

  1. 1 Department of Critical Care Medicine, Xi'an Traditional Chinese Medicine Brain Disease Hospital, Xi'an 710038, China; 2 First Department of Digestive Diseases, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang 7120000, China

  • Received:2024-11-25 Online:2025-08-15 Published:2025-08-28
  • Contact: Liu Wendong, Email: 523260239@qq.com
  • Supported by:

    Project Supported by Key Studio of Shaanxi Bureau of Traditional Chinese Medicine (No.201832)

摘要:

目的 基于网络药理学及实验验证探究小檗碱对结肠炎的保护作用及机制。方法 网络药理学分析的数据检索时间为2023年6月。结合PharmMapper、Swiss Target Prediction、Genecards等数据库筛选小檗碱中含有的有效成分及作用靶点,利用Cytoscape 3.9.1软件构建“疾病-靶点-化合物”网络。结合STRING数据库构建蛋白相互作用(protein-protein interaction,PPI)网络筛选核心靶点;使用David数据库对共同靶点进行基因本体功能(gene ontology,GO)与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,获取潜在信号通路,并对结果进行可视化。建立脂多糖(lipopolysaccharide,LPS)诱导的结肠腺癌细胞Caco-2细胞模型,探讨小檗碱治疗结肠炎的效果及作用机制。结果 通过数据库整理分析筛选出药物和疾病相关交集靶点共86个,主要核心靶点为JAK3、VEGFR2、ANXA5、NQO1;GO和KEGG富集分析结果表明,小檗碱主要是通过JAK3/STAT1信号通路发挥治疗结肠炎的作用。细胞实验结果显示,小檗碱可以抑制JAK3/STAT1信号通路,抑制LPS诱导的Caco-2细胞中白细胞介素-1β(interleukin-1β,IL-1β)的表达,减轻炎症反应。结论 小檗碱可以通过抑制JAK3-STAT1信号通路减少LPS诱导Caco-2细胞的炎症反应,增强肠道屏障功能,达到治疗结肠炎的作用。

关键词:

结肠炎, 小檗碱, 网络药理学, 炎症, JAK3-STAT1

Abstract:

Objective To explore the protective effect and mechanism of berberine on colitis based on network pharmacology and experimental verification. Methods The data retrieval time for the network pharmacology analysis was June 2023. The databases, such as PharmMapper, SwissTarget Prediction, and Genecards, were used to screen the active ingredients and targets in berberine, and a "disease target compound" network was constructed by the Cytoscape 3.9.1 software. A protein-protein interaction (PPI) network was constructed based on the STRING database to screen the core targets. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on common targets were performed using the David database to obtain the potential signaling pathways and to visualize the results. A lipopolysaccharide (LPS) -induced Caco-2 cell model of colon adenocarcinoma cells was established to investigate the efficacy and mechanism of berberine in treating colitis. Results Through database analysis and sorting, a total of 86 intersecting targets related to drugs and diseases were identified, and the main core targets were JAK3, VEGFR2, ANXA5, and NQO1. The GO and KEGG enrichment analyses results indicated that berberine mainly exerted its therapeutic effect on colitis through the JAK3/STAT1 signaling pathway. Cell experiments have shown that berberine can inhibit the JAK3/STAT1 signaling pathway, suppress the levels of interleukin-1β in Caco-2 cells induced by LPS, and alleviate inflammatory responses. Conclusions Berberine can reduce LPS-induced inflammatory response in Caco-2 cells inhibiting the JAK3-STAT1 singnaling pathway, enhance intestinal barrier function, and achieve therapeutic effects on colitis.

Key words:

Colitis, Berberine, Network pharmacology, Inflammation, JAK3-STAT1