基于网络药理学对乌药汤治疗原发性痛经作用机制的研究

Study on the mechanism of Wuyao Decoction in treating primary dysmenorrhea based on network pharmacology

目的:利用网络药理学方法探讨乌药汤治疗原发性痛经的作用机制。方法:借助中药系统药理学分析平台(TCMSP)筛选乌药汤的活性成分;通过Pharmmapper数据库筛选活性成分潜在靶点基因,使用GeneCards数据库得到原发性痛经相关基因靶点;将活性成分的潜在靶点基因与原发性痛经相关基因进行比对,得到乌药汤治疗原发性痛经的潜在靶点基因;使用KOBAS3.0数据库对靶点基因功能(gene ontology,GO)和KEGG通路进行分析,得到乌药汤治疗原发性痛经的重要调节通路;采用Cytoscape3.6.1软件构建“成分-靶点-通路”网络;将筛选得到的主要活性成分和关键靶点进行分子对接验证。结果:从乌药汤中共筛选出菜蓟苦素、金圣草(黄)素、异黄檀素、甘草素f等31个活性成分,涉及包括ESR1、CASP3、MMP9、HRAS在内的23个基因靶点,影响了内分泌抵抗(Endocrine resistance)、雌激素受体信号传导通路(Estrogen signaling pathway)和催乳激素信号通路(Prolactin signaling pathway)等95条与原发性痛经相关的信号通路。分子对接结果显示,筛选得到的主要活性成分与关键靶点有较强结合,其中菜蓟苦素(cynaropicrin)和关键靶点的结合能力与阳性药接近。结论:本研究通过构建“成分-靶点-通路”网络图,揭示了乌药汤能通过多成分、多靶点、多通路发挥药效,为进一步阐释乌药汤治疗原发性痛经作用机制提供了科学依据。

OBJECTIVE To explore the mechanism of Wuyao decoction in treating primary dysmenorrhea by network pharmacology.METHODS The traditional Chinese medicine system pharmacology analysis platform(TCMSP)was used to screen the active components of Wuyao decoction.The potential target genes of active ingredients were screened by Pharmmapper database.The target genes related to primary dysmenorrhea were obtained by GeneCards database.Then the potential targets of active ingredients were compared with the genes related to primary dysmenorrhea,and the potential target genes of Wuyao decoction for primary dysmenorrhea was obtained.KOBAS3.0 database was used to analyze the gene ontology(GO)and KEGG pathway,and the important regulatory pathway of wuyao decoction in the treatment of primary dysmenorrhea was obtained.The"components-targets-pathways"network was constructed by using Cytoscape 3.6.1 software.The main active components and key targets were screened for molecular docking verification.RESULTS A total of 31 active components including Escherichia coli,Dioscorea zingiberensis,Isoflavone,and Glycyrrhizin f were selected from Wuyao decoction,involving 23 target genes including ESR1,CASP3,MMP9 and HRAS.And 95 signal pathways related to primary dysmenorrhea,such as Endocrine resistance,Estrogen signaling pathway and Prolactin signaling pathway were found after analyzing.Molecular docking results showed that the main active components were strongly bound to key targets,and the binding ability of cynaropicrin and key targets was close to that of positive drugs.CONCLUSION By constructing the“components-target genes-pathways”network,the study reveals the characteristics of Wuyao decoction exerting its effects through multi-components,multi-targets and multi-pathways,which provides a scientific basis for further elucidation of Wu Yao decoction in the treatment of primary dysmenorrhea.