基于网络药理学与孟德尔随机化探讨姜黄素治疗2型糖尿病的药理学机制

Exploring the Pharmacological Mechanism of Curcumin in the Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology and Mendelian Randomisation

摘要: 目的：通过网络药理学与孟德尔随机化的结合探讨姜黄素治疗2型糖尿病的药理学机制。方法：姜黄素的药物靶点通过pharmapper数据库、Swiss Target Prediction数据库获得，2型糖尿病的疾病靶点通过GeneCards数据库获得，将药物靶点与疾病靶点进行合并以获得潜在的治疗靶点，蛋白质之间相互作用(PPI)数据从String数据库中获得，通过R语言对治疗靶点进行GO与KEGG分析，通过IEU OPEN GWAS Project数据库获得暴露数据与结局数据的相关信息，并通过语言进行孟德尔随机化分析。结果：姜黄素的药物靶点预测到了111个，2型糖尿病的疾病靶点有921个，治疗靶点有27个，对这些治疗靶点KEGG分析发现主要通路为凋亡信号通路、TNF信号通路、IL-17信号通路等，核心治疗靶点为CASP3、MMP2、SIRT1等。结论：姜黄素通过多靶点、多通路、多生物学过程对2型糖尿病起到治疗作用，这与中医学核心观念相一致。

Abstract: Objective: To explore the pharmacological mechanism of curcumin in the treatment of type 2 diabetes through the combination of network pharmacology and Mendel randomization. Methods: The drug targets of curcumin were obtained from pharmapper database and Swiss Target Prediction database, the disease targets of type 2 diabetes were obtained from GeneCards database, the drug targets and disease targets were combined to obtain potential therapeutic targets, the protein-protein interaction (PPI) data was obtained from String database, the treatment targets were analyzed by GO and KEGG through R language, the relevant information of exposure data and outcome data was obtained through IEU OPEN GWAS Project database, and Mendelian randomization analysis was conducted through language. Results: 111 drug targets were predicted for curcumin, 921 disease targets for type 2 diabetes, and 27 therapeutic targets. KEGG analysis of these therapeutic targets found that the main pathways were apoptosis signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and the core therapeutic targets were CASP3, MMP2, SIRT1, etc. Conclusion: Curcumin plays a therapeutic role in type 2 diabetes through multiple targets, multiple pathways and multiple biological processes, which is consistent with the core concept of traditional Chinese medicine.