基于网络药理学分析愈癫汤治疗精神分裂症的作用机制

Analysis of the Effect Mechanism of Yudian Decoction in the Treatment of Schizophrenia Based on Network Pharmacology

摘要: 目的：运用网络药理学方法分析愈癫汤治疗精神分裂症的作用机制。方法：利用中药系统药理学分析平台(TCMSP)，筛选愈癫汤中口服生物利用度(OB) ≥ 30%且类药性(DL) ≥ 0.18的有效成分，并通过UniProt数据库确定其靶点。同时，从OMIM、DrugBank、GeneCards和TTD数据库中获取精神分裂症相关靶点。使用Cytoscape软件构建成分–靶点网络图，并通过DAVID数据库对靶点进行GO和KEGG富集分析。结果：从TCMSP中筛选出87个活性成分，去重后得到76个成分，涉及136个潜在靶点。通过Venn图将1445个精神分裂症靶点与潜在靶点取交集，获得100个有效作用靶点。GO和KEGG富集分析结果显示，这些靶点主要参与化学性突触传递、药物反应、腺苷酸环化酶激活的肾上腺素能受体信号通路及G蛋白偶联受体信号通路等生物过程，并涉及神经递质受体活性、细胞外配体门控离子通道活性等分子功能。结论：愈癫汤可能通过调控MAPK、cAMP、T细胞受体、IL-17及钙信号通路等发挥治疗作用。本研究为愈癫汤治疗精神分裂症的机制提供了理论依据，并为后续实验研究奠定了基础。

Abstract: Objective: To analyze the mechanism of Yudian Decoction in treating schizophrenia using network pharmacology methods. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was utilized to screen active components of Yudian Decoction with oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18. Potential targets of these components were identified using the UniProt database. Meanwhile, schizophrenia-related targets were obtained from the OMIM, DrugBank, GeneCards, and TTD databases. A component-target network was constructed using Cytoscape software, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the targets were performed using the DAVID database. Results: A total of 87 active components were screened from TCMSP, and after deduplication, 76 components involving 136 potential targets were identified. By intersecting 1445 schizophrenia-related targets with the potential targets using a Venn diagram, 100 effective targets were obtained. GO and KEGG enrichment analyses revealed that these targets are primarily involved in biological processes, such as chemical synaptic transmission, drug response, adenylate cyclase-activating adrenergic receptor signaling pathway, and G protein-coupled receptor signaling pathway. They are also associated with molecular functions such as neurotransmitter receptor activity and extracellular ligand-gated ion channel activity. Conclusion: Yudian Decoction may exert its therapeutic effects by regulating the MAPK, cAMP, T-cell receptor, IL-17, and calcium signaling pathways. This study provides a theoretical basis for the mechanism of Yudian Decoction in treating schizophrenia and lays the foundation for further experimental research.