探析越鞠丸和柴胡疏肝散“同病异治”抑郁症的作用机制

Analysis of Antidepressant Mechanism of Yueju Pill and Chaihu Shugan Powder in Treating Depression with “the Same Disease with Different Treatments”

摘要: 目的：基于网络药理学和生物信息学方法探讨越鞠丸和柴胡疏肝散“同病异治”抑郁症的作用机制。方法：利用TCMID、Batman-TCM获取越鞠丸与柴胡疏肝散各自的有效活性成分和作用靶点；通过基因表达集(GEO)芯片数据库筛选抑郁症差异基因，DrugBank、GeneCards、OMIM、TTD筛选抑郁症相关靶点基因；运用Cytoscape和String构建靶点相互作用网络PPI，并通过Cytoscape的Network Analyzer工具对靶点进行拓扑分析，插件ClusterViz的MCODE算法进行模块分析；利用DAVID对靶点进行GO和KEGG分析。结果：两个方剂中有310个共同靶点与抑郁症有关，越鞠丸特有抗抑靶点有20个，柴胡疏肝散特有抗抑靶点有52个。这两种药物可能通过INS、ALB、BDNF、IL6、FOS等关键蛋白所在的神经活性配体–受体相互作用、Calcium信号通路和细胞缝隙连接等发挥抗抑郁的作用。越鞠丸的特有靶点SCNN1G、SCNN1B、SCNN1A所在的醛固酮调节的钠重吸收、味觉转导信号通路揭示了抗抑郁机制；柴胡疏肝散的特有靶点AKT1、HRAS、MAPK1蛋白所在的癌症通路、ErbB信号通路等揭示了不同的抗抑郁机制。结论：越鞠丸和柴胡疏肝散由于组分差异，既可以通过相同靶点抗抑郁，也可以通过特有靶点抗抑郁。本研究对两种方剂中药物靶点和通路进行可视化网络分析，进而初步阐明“同病异治”抑郁症的科学内涵。

Abstract: Objective: Based on network pharmacology and bioinformatics methods, to explore the mechan-ism of Yueju Pill and Chaihu Shugan Powder in treating depression in “the same disease with dif-ferent treatments”. Methods: TCMID and Batman-TCM were used to obtain the active components and targets of Yueju Pill and Chaihu Shugan Powder respectively; use Gene Expression Omnibus (GEO) and genetic disease databases to screen the differences of genes in depression; use DrugBank, Gene Cards, OMIM, TDD to screen related proteins to depression; use Cytoscape and String to construct the protein interaction network (PPI). Through the Network Analyzer tool of Cytoscape, the topology of the target was analyzed, and ClusterViz’s MCODE algorithm was used for module analysis; use DAVID for GO and KEGG analysis of targets. Results: Among the two formulations, 310 common targets were related to depression, among which 20 were specific anti-depressants of Yueju Pill and 52 were specific anti-depressants of Chaihu Shugan Powder. These two drugs may play an antidepressant role in the neural-active ligand-receptor interactions and Calcium signaling pathways of key proteins such as INS, ALB, BDNF, IL6, FOS and so on. The aldosterone regulating sodium reabsorption and taste transduction pathways of the specific targets SCNN1G, SCNN1B and SCNN1A of Yueju Pill revealed the antidepressant mechanism; AKT1, HRAS, MAPK1 in the cancer pathways and ErbB signaling pathways, which are specific targets of Chaihu Shugan Powder, reveal different antidepressant mechanisms. Conclusion: Due to the difference in components, Yueju Pill and Chaihu Shugan Powder can be used as anti-depressants at the same or specific targets. In this study, the visual network analysis of drug targets and pathways in the two formulations was carried out to preliminarily clarify the scientific connotation of “treating depression in the same disease with different treatments”.