基于网络药理学的柴胡疏肝散抗抑郁机制研究

Study on the mechanism of anti-depression of Chaihu Shugan powder based on network pharmacology

目的:基于网络药理学方法探究柴胡疏肝散抗抑郁的分子机制。方法:应用中药系统药理学分析平台(Traditional Chinese Medicines Systems Pharmacology Platform,TCMSP)数据库筛选柴胡疏肝散的有效药味成分,并应用TCMSP和Swiss Target Prediction数据库预测成分靶点。应用DrugBank、OMIM和GeneCards数据库查找抑郁症靶点,并与成分靶点相映射,得到柴胡疏肝散治疗抑郁症的潜在靶点。借助Cytoscape3.7.2构建成分-靶点(Compounds-Targets,C-T)网络和蛋白质-蛋白质相互作用(Protein-protein Interaction,PPI)网络,David数据库进行GO和KEGG富集分析。结果:预测柴胡疏肝散中有94个成分可治疗抑郁症,涉及59个靶点。关键成分包括hyndarin、β-谷甾醇、豆甾醇、7-甲氧基-2-甲基异黄酮、山柰酚、槲皮素等。GABRA3、GABRA1、GABRB2等核心靶点主要涉及γ-氨基丁酸(Gamma-aminobutyric Acid,GABA)A受体复合物、质膜的整体成分、氯通道复合物等18个细胞组分,GABA-A受体活性、胞外配体门控离子通道活性、氯通道活性等23个分子功能,GABA信号通路、氯化物跨膜转运、离子跨膜转运等91个生物过程,神经活性配体-受体相互作用、尼古丁成瘾、GABA能突触等13条通路信息。结论:柴胡疏肝散通过多成分、多靶点、多途径发挥治疗抑郁症的作用。

Objective:To explore the antidepressant mechanism of Chaihu Shugan powder(柴胡疏肝散)by using network pharmacology methods.Methods:TCMSP was used to screen the active compounds of Chaihu Shugan powder.TCMSP,PubChem and Swiss Target Prediction were used to predict targets of compounds.Drugbank,OMIM and GeneCards were used to find targets of depression,and mapping with targets of compounds in order to get the potential targets of Chaihu Shugan powder in the treatment of depression.Cytoscape3.7.2 was used to establish the Compounds-Targets(C-T)network and Protein Interaction(PPI)network,and David database was used to perform GO and KEGG enrichment analysis.Result:It was predicted that 94 compounds of Chaihu Shugan powder can treat depression,involving 59 targets.Key compounds included hydarin,beta-sitosterol,stigmasterol,7-Methoxy-2-methyl isoflavone,kaempferol,quercetin,etc.Core targets such as GABRA3,GABRA1,GABRB2 mainly involved 18 cellular components such as GABA-A receptor complex,integral component of plasma membrane,chloride channel complex,23 molecular functions such as GABA-A receptor activity,extracellular ligand-gated ion channel activity,chloride channel activity,91 biological processes such as gamma-aminobutyric acid signaling pathway,chloride transmembrane transport,ion transmembrane transport,and 13 signal pathways such as neuroactive ligandreceptor interaction,nicotine addiction,GABAergic synapse.Conclusion:Chaihu Shugan powder plays a role in the treatment of depression through multi-component,multi-target and multi-pathway.