基于网络药理学和分子对接探讨姜黄素治疗溃疡性结肠炎的分子机制

Molecular Mechanism of Curcumin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

目的基于网络药理学方法和分子对接技术预测姜黄素改善溃疡性结肠炎(UC)的关键靶点和潜在作用机制。方法通过数据库筛选获取姜黄素分子靶标及UC疾病靶点,利用Venny 2.1在线平台获取交集靶点,将药物疾病共有靶点导入STRING数据库构建蛋白互作(PPI)网络,借助Cytoscape软件进行拓扑学参数分析并筛选核心靶点,利用DAVID数据库进行GO功能注释和KEGG通路富集分析,最后进行分子对接以预测姜黄素与核心靶标的结合活性。结果共获得姜黄素潜在作用靶点324个,UC靶点2907个,姜黄素与UC交集靶点168个;通过PPI网络获得姜黄素改善UC的关键靶点,包括SRC、MAPK1、STAT3、AKT1、HSP90AA1和PTPN11,主要涉及细胞凋亡过程负调控、蛋白质磷酸化、癌症相关通路、脂质和动脉粥样硬化、C型凝集素受体信号通路等通路;分子对接结果显示,姜黄素对潜在核心靶点具有良好的亲和力,其中STAT3结合度最高。结论姜黄素可以通过多靶点、多途径系统地改善UC,为后续运用姜黄素治疗UC的新药开发和临床研究提供了理论依据。

Objective To predict the key targets and potential mechanisms of curcumin in improving ulcerative colitis(UC)based on network pharmacology and molecular docking.Methods Curcumin molecular targets and UC disease targets were obtained through database screening.Venny 2.1 online platform was used to obtain intersection targets.The common targets of drug diseases were imported into STRING database to construct protein interaction(PPI)network.Cytoscape software was used to analyze topological parameters and screen core targets.DAVID database was used for GO function annotation and KEGG pathway enrichment analysis.Finally,molecular docking was performed to predict the binding activity of curcumin and core targets.Results A total of 324 potential targets of curcumin,2907 UC targets,and 168 intersection targets of curcumin and UC were obtained.The key targets of curcumin to improve UC obtained by PPI network included SRC,MAPK1,STAT3,AKT1,HSP90 AA1 and PTPN11,mainly involving negative regulation of apoptosis process,protein phosphorylation,cancer-related pathways,lipids and atherosclerosis,C-type lectin receptor signaling pathway and other pathways;molecular docking results showed that curcumin had good affinity for potential core targets,among which STAT3 had the highest binding degree.Conclusion Curcumin can systematically improve UC through multiple targets and multiple pathways,which provides a theoretical basis for the subsequent development and clinical research of new drugs for the treatment of UC with curcumin.