基于网络药理学探讨苦茶碱治疗特应性皮炎的作用机制

Exploring the Mechanism of Action of Theacrine in Treating Atopic Dermatitis Based on Network Pharmacology

摘要: 目的：以网络药理学为基础，探索苦茶碱(Theacrine)治疗特应性皮炎(Atopic dermatitis, AD)的潜在靶点并分析其作用机制。方法：通过Swiss Taget Predictions数据库探索苦茶碱的潜在作用靶点。利用GeneCards和OMIM数据库搜索与特应性皮炎相关的靶点。将AD疾病靶点数据合并去重以后苦茶碱靶点导入jvenn绘制韦恩图，从而获得交集靶点。将交集靶点导入STRING构建苦茶碱与AD的蛋白互作网络图，并通过Cytoscape3.7.2软件构建PPI网络。进行基因本体论分析(GO)和基于KEGG数据库的通路富集分析。结果：共筛选出苦茶碱潜在作用靶点68个；特应性皮炎疾病靶点2158个；交集靶点23个；其中CTSS、SYK、BACE1、HDAC1、ADORA2A为蛋白互作网络图筛选出的苦茶碱治疗特应性皮炎的核心靶点；通过P值 < 0.01，GO富集分析获得738个生物学过程、70个细胞组分、70个分子功能；KEGG富集分析获得23条信号通路。结论：苦茶碱可能是通过CTSS、SYK、BACE1、HDAC1、ADORA2A等关键基因靶点，经Notch信号通路、神经活性配体信号传导通路、类固醇激素生物合成通路、FcεRI信号通路等发挥治疗特应性皮炎的作用。

Abstract: Objective: To investigate the mechanism of action of theacrine in treating atopic dermatitis (AD) using network pharmacology. Method: Explore potential targets for theacrine using the Swiss Target Predictions database. Search for targets associated with atopic dermatitis using the GeneCards and OMIM databases. After merging and deduping AD disease target data, the theobromine targets were imported into JVenn to generate a Venn diagram, thereby identifying the intersection targets. Import the intersecting targets into STRING to construct a protein-protein interaction (PPI) network diagram between theobromine and AD. Using Cytoscape 3.7.2 software, build the PPI network. Perform gene ontology (GO) analysis and pathway enrichment analysis based on the KEGG database. Results: A total of 68 potential targets for theacrine and 2158 targets for atopic dermatitis were identified. The intersection yielded 23 common targets, among which CTSS, SYK, BACE1, HDAC1, and ADORA2A were selected as core targets for theobromine treatment of atopic dermatitis based on the protein interaction network analysis. With a P-value < 0.01, GO enrichment analysis identified 738 biological processes, 70 cellular components, and 70 molecular functions; KEGG enrichment analysis identified 23 signaling pathways. Conclusion: theacrine may exert its therapeutic effects on atopic dermatitis by targeting key genes such as CTSS, SYK, BACE1, HDAC1, ADORA2A, acting through pathways including the Notch signaling pathway, neuroactive ligand-signaling pathway, steroid hormone biosynthesis pathway, and FcεRI signaling pathway.