基于网络药理学和分子对接探索半夏厚朴汤、四逆散和越鞠丸“同病异治”抑郁症的作用机制

Based on Network Pharmacology and Molecular Docking to Explore the Mechanisms of Banxiahoupo Decoction, Sini Powder and Yueju Pill in the Treatment of Depression by “Same Disease with Different Treatments”

摘要: 目的：本文通过网络药理学和分子对接技术探索半夏厚朴汤、四逆散和越鞠丸“同病异治”抑郁症的作用机制。方法：通过TCMSP和BATMAN-TCM数据库整理半夏厚朴汤、四逆散和越鞠丸的活性成分和靶点信息，联合GSE87610生物芯片和PharmGKB、DrugBank、OMIM、TTD、GeneCards五个疾病数据收集抑郁症靶点。利用Cytoscape3.8.0构建“活性成分–药物靶点”互作网络，筛选重要成分和关键靶点；基于Venny2.1.0获取三种复方和抑郁症的共同靶点，使用String在线分析工具获取蛋白质互作网络图，采用DAVID在线数据库对核心靶点进行GO富集和KEGG信号通路分析。筛选“活性成分–药物靶点”互作网络中Degree排名前五的活性成分和三种中药复方和抑郁症共有靶点PPI排名前五的靶点分别作为配体和受体，用PyMol、Autodock和Vina软件对活性成分和蛋白质进行分子对接。结果：半夏厚朴汤中有效成分192个、潜在靶点1544个，四逆散中有效成分275个、潜在靶点1442个，越鞠丸中有效成分177个、潜在靶点1364个，抑郁症靶点1337个，得到三种中药复方和抑郁症共有靶点347个。KEGG信号通路分析共获得153条，涉及神经活性配体–受体相互作用、癌症的途径cAMP信号通路、钙信号通路、PI3K-Akt信号通路等。筛选得到的活性成分为黄连碱、槲皮素、壬酸、棕榈酸和缬氨酸；关键靶点为AKT1、INS、TP53、IL6和TNF；对接结果显示五种活性成分和五种蛋白均具有较好的结合能力。结论：半夏厚朴汤、四逆散和越鞠丸三种复方存在着相同和不同的抗郁成分和靶点，通过分析靶点和通路，加以分子对接技术辅助验证结合活性，初步阐明三者“同病异治”抑郁症的科学内涵。

Abstract: Objective: Based on network pharmacology and molecular docking to explore the mechanisms of Banxiahoupo Decoction, Sini Powder and Yueju Pill treating depression with “Same Disease with Different Treatments”. Methods: The active ingredients and target information of Banxiahoupo Decoction, Sini Powder and Yueju Pill were sorted by TCMSP and BATMAN-TCM database, and depression targets were collected by combining GSE87610 chip and PharmGKB, DrugBank, OMIM, TTD and GeneCards. Use Cytoscape3.8.0 to draw the interaction network of “active ingredients-drug targets”, then screen important ingredients and key targets. Venny2.1.0 was used to get the common target of three kinds of compound prescription and depression, PPI was drawn by String online analysis tool, and GO enrichment and KEGG signal pathway analysis were carried out on the key targets by DAVID online database. Screening the top five active ingredients in the “active ingredient-drug target” interaction network and the top five targets in PPI, which are common targets of three traditional Chinese medicine compounds and depression, as ligands and receptors respectively. Use PyMol, Autodock and Vina software for molecular docking of active ingredients and protein. Results: There were 192 active ingredients and 1544 potential targets in Banxiahoupo Decoction, 275 active ingredients and 1442 potential targets in Sini Powder, 177 active ingredients and 1364 potential targets in Yueju Pill, and 1337 targets in depression. There were 347 targets shared by three traditional Chinese medicine compounds and depression. A total of 153 KEGG signal paths were obtained, which involved neuroactive ligand-receptor interaction, cAMP signaling pathway, calcium signaling pathway, PI3K-Akt signaling pathway and so on. The screened active ingredients are coptisine, quercetin, nonanoic acid, palmitic acid and valine. The key targets are AKT1, INS, TP53, IL6 and TNF. The docking results showed that the five active ingredients and five proteins had good binding ability. Conclusion: Banxiahoupo Decoction, Sini Powder and Yueju Pill have the same and different anti-depression components and targets. By analyzing the targets and pathways and verifying the binding activity with the aid of molecular docking technology, the scientific connotation of treating depression with “Same Disease with Different Treatments” among the three compounds is preliminarily clarified.