[关键词]
[摘要]
目的 构建逍遥散单味药-成分-共有靶点网络、蛋白相互作用网络,探究逍遥散“异病同治”抑郁症和糖尿病的共同作用机制。方法 通过TCM database@Taiwan、TCMID、Batman-TCM数据库结合文献挖掘获取逍遥散的化学成分和作用靶点,结合CTD、TTD、PharmGKB、OMIM、Gencards、Drugbank数据库获取逍遥散治疗抑郁症和糖尿病的作用靶点。采用Cytoscape软件绘制单味药-成分-共有靶点网络。采用Metascape工具对逍遥散治疗抑郁症和糖尿病的共有靶点进行GO生物过程分析、Reactome通路分析、KEGG通路分析、蛋白相互作用网络构建和模块分析。分别采用BioGPS、Genecards分析通路关键靶点的组织分布和亚细胞分布,并采用Cytoscape软件绘制组织-靶点、亚细胞-靶点网络。采用DisGeNET数据库对通路关键靶点进行蛋白归属。结果 逍遥散治疗糖尿病和抑郁症共病涉及免疫炎症反应,与G蛋白偶联受体、胰岛素及其受体、单胺类神经递质相关,通过调节环磷酸腺苷(cAMP)信号通路、钙信号通路、磷脂酰肌醇3激酶-蛋白激酶B(PI3K-Akt)信号通路等实现。结论 逍遥散治疗抑郁症和糖尿病共病的作用机制涉及脑源性神经营养因子(BDNF)相关信号通路、G蛋白偶联受体、单胺类神经递质、胰岛素及其受体等调节过程,可为深入阐释逍遥散抗抑郁作用特点及其药理机制提供依据。
[Key word]
[Abstract]
Objective In this paper, herb-component-common target network and protein interaction network were constructed to study the mechanism of Xiaoyao Powder in the treatment of depression and diabetes for exploring the common mechanism of Xiaoyao Powder in treating these two diseases. Methods TCM database@Taiwan, TCMID, Batman-TCM database and literature mining were used to obtain the components and targets of Xiaoyao Powder, combined with CTD, TTD, PharmGKB, OMIM, Gencards, and Drugbank databases to obtain the targets of Xiaoyao Powder in the treatment of depression and diabetes. The herb-component-common target network was constructed by Cytoscape software. The tool of Metascape was used to perform GO biological processes analysis, Reactome pathway analysis, KEGG pathway analysis, protein interaction networks construction and module analysis on the common targets of Xiaoyao Powder in the treatment of depression and diabetes. BioGPS database and Genecards database were used to analyze the tissue distribution and subcellular distribution of the hub targets, and the tissue-target network and subcellular-target network were constructed by Cytoscape. Protein class was performed on hub pathway targets by DisGeNET database. Results The results showed that the immune and inflammatory responses, G protein-coupled receptors, insulin and insulin receptors, and monoamine neurotransmitter were involved in the treatment of these two diseases by regulating cAMP signaling pathway, Calcium signaling pathway and PI3K-Akt signaling pathway by Xiaoyao Powder. Conclusion It provides a direction for further research on Xiaoyao Powder’s common mechanism in treating depression and diabetes. It suggests that the efficacy of Xiaoyao Powder in the treatment of depression and diabetes are mainly involved with the regulation of BDNF-related signaling pathways, the process of G protein-coupled receptors, monoamine neurotransmitter and the insulin and insulin receptors, which will benefit to the further investigation on the declaration of the characteristics of the pharmacological mechanism of Xiaoyao Powder.
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[基金项目]
国家“重大新药创新创制”科技重大专项课题(2017ZX09301047);山西省科技重点研发计划(201603D3113013);山西省科技重点研发计划(201603D321077);山西省科技重点研发计划(201701D121137);地产中药功效物质研究与利用山西省重点实验室项目(201605D111004);山西省科技创新重点团队项目(201605D131045-18)