基于网络药理学方法探讨十二味乌梅汤治疗失眠的作用机制

Exploration of the mechanism of Wumei Decoction(12 Chinese herbs)in treating insomnia based on network pharmacology

目的:应用网络药理学方法探讨十二味乌梅汤治疗失眠的潜在作用机制。方法:通过Batman、TCMSP数据库检索十二味乌梅汤药物的相关活性成分和作用靶点,采用Cytocape构建十二味乌梅汤-失眠-潜在靶点网络图。通过交互靶点GO功能分析和KEGG通路富集分析研究十二味乌梅汤和失眠的相关生物学过程和信号通路。将十二味乌梅汤的关键活性成分与核心靶点进行分子对接验证。结果:得到十二味乌梅汤中134种有效活性成分,187个潜在治疗靶点,153个靶点与失眠关系密切。通过GO功能分析和KEGG通路富集分析发现,十二味乌梅汤治疗失眠的机制最有可能和脂质与动脉粥样硬化、流体剪切应力与动脉粥样硬化、糖尿病并发症信号通路、化学致癌-受体激活通路等相关。通过分子对接验证表明部分活性成分与核心靶点之间具有良好的结合性,其中槲皮素为主要活性成分中潜在靶标数最多。结论:十二味乌梅汤可通过调节不同基因来调控不同的信号通路达到治疗失眠的作用,体现了中药复方具有多成分、多通路、多靶点的特点,为进一步深入的临床研究提供科学依据。

Objective:To explore the potential mechanism of Wumei Decoction(12 Chinese herbs)in the treatment of insomnia by network pharmacology.Methods:The related active ingredients and targets of Wumei Decoction(12 Chinese herbs)were searched through Batman and TCMSP databases,and Cytocape was adopted to construct the network diagram of Wumei Decoction(12 Chinese herbs),insomnia and potential targets.The related biological processes and signaling pathways of Wumei Decoction(12 Chinese herbs)and insomnia were studied by interactive target GO function analysis and KEGG pathway enrichment analysis.The key active ingredients of Wumei Decoction(12 Chinese herbs)and the core targets were verified by molecular docking.Results:A total of 134 active ingredients and 187 potential therapeutic targets were obtained from Wumei Decoction(12 Chinese herbs),and 153 targets were closely related to insomnia.Through GO functional analysis and KEGG pathway enrichment analysis,it was found that the mechanism of Wumei Decoction(12 Chinese herbs)in treating insomnia was most likely related to lipid and atherosclerosis,fluid shear stress and atherosclerosis,diabetes complication signaling pathway,and chemical carcinogenic-receptor activation pathway.Molecular docking verification showed that some active ingredients had good binding with core targets,among which quercetin was the main active ingredient with the largest number of potential targets.Conclusion:Wumei Decoction(12 Chinese herbs)can regulate different signaling pathways by regulating different genes to achieve the effect of treating insomnia,which reflects the characteristics of Chinese medicine compound with multi-components,multi-pathways and multi-targets,and provides scientific basis for further clinical research.