天南星-生姜药对治疗疼痛机制的网络药理学研究

Study on mechanism of Tiannanxing-Shengjiang drug pair in treating pain based on network pharmacology

目的:运用网络药理学方法,分析天南星-生姜药对治疗疼痛的潜在靶点和作用机制。方法:通过中药系统药理学数据库和分析平台(TCMSP)检索出天南星和生姜的活性成分和靶点。以“pain”为关键词,通过Dis Ge Net数据库检索出和疼痛相关的靶基因,并得到共同的靶点。通过String数据库构建蛋白互作网络图(protein-protein interaction,PPI)并进行分析,筛选出重要靶点。通过DAVID网站对共同靶点进行GO富集分析和KEGG通路富集分析。结果:从天南星和生姜药对中共筛选出10个有效成分,药物与疾病有63个共同靶点,包括CNR1、ESR1、MAPK3、CYP3A4、JUN、HDAC1等。GO分析得出的生物学过程包括炎症反应过程、EKR1和EKR2级联的正向调控、RNA聚合酶II启动子转录过程、G蛋白偶联受体信号通路等。KEGG富集共得到53条通路,其中与疼痛关系较为密切的包括钙信号通路、胆碱能突触信号传递、雌激素信号通路、癌症途径、5-羟色胺能通路等。结论:天南星-生姜药中的豆甾醇、β-谷甾醇、二氢辣椒碱等有效成分可能通过作用于CNR1、ESR1、MAPK3、CYP3A4、JUN、HDAC1等靶点,调节细胞内钙离子传导、胆碱能突出信号传递、癌症信号通路等对多种类型疼痛均可发挥作用,为进一步的实验设计提供理论基础。

Objective:To analyze the potential targets and mechanisms of Tiannanxing-Shengjiang drug pair in the treatment of pain using the network pharmacology approach.Methods:The TCMSP database was used to screen the active components and targets of the drug pair"Tiannanxing-Shengjiang".The target genes related to pain were retrieved from the DisGeNet database,and the intersection targets were obtained.Protein-protein interaction(PPI)network was constructed and analyzed by string database to screen out the important targets.GO enrichment analysis and KEGG pathway enrichment analysis of intersection targets were performed through the DAVID website.Results:A total of 10 active ingredients were screened from Tiannanxing-Shengjiang drug pair and we found 63 intersection targets between drug and disease,including CNR1,ESR1,MAPK3,CYP3A4,JUN,and HDAC1.The biological processes derived from GO analysis included inflammatory response,positive regulation of EKR1 and EKR2 cascade,positive regulation of transcription from RNA polymerase II promoter,and G-protein coupled receptor signaling pathway.A total of 53 pathways were obtained from KEGG,among which those more closely related to pain included calcium signaling pathway,cholinergic synapse,estrogen signaling pathway,cancer pathway,and serotonergic synapse.Conclusion:The active ingredients such as Stigmasterol,β-sitosterol,and dihydrocapsaicin in the Tiannanxing-Shengjiang pair may act on various types of pain by acting on CNR1,ESR1,MAPK3,CYP3A4,JUN,HDAC1 and other targets to regulate intracellular calcium ion conduction,cholinergic prominent signaling,cancer signaling pathway and so on,providing a theoretical basis for further experimental design.