减味寿胎丸治疗自然流产活性成分和作用机制的网络药理学研究

Network pharmacology research on active ingredients and mechanism of Jianwei Shoutai Pills in the treatment of spontaneous abortion

目的基于网络药理学,筛选减味寿胎丸(JWSTP)主要活性成分,预测其活性成分的作用靶点,探讨JWSTP治疗自然流产(SA)的作用机制。方法应用中药系统药理学分析平台筛选JWSTP的活性成分和作用靶点,SA的疾病靶点筛选自GeneCards和OMIM数据库,预测JWSTP治疗SA的潜在靶点;对潜在靶点构建蛋白互作网络,在在线STRING平台实现;基因本体生物过程和京都基因和基因组数据库的功能注释分析在DAVID 6.8平台实现,得到关键通路,构建活性成分-潜在作用靶标-关键通路网络。结果共获得JWSTP的活性成分18个,得到JWSTP治疗SA的潜在靶点108个,关键靶点有转录因子AP-1、肿瘤坏死因子、蛋白激酶AKT1、白介素-6、血管内皮生长因子A和丝裂原活化蛋白激酶1等,这些靶点主要涉及RNA聚合酶Ⅱ启动子转录的正调控、细胞凋亡和炎症应答等生物过程,并主要富集在PI3K-Akt、丝裂原活化蛋白激酶、肿瘤坏死因子等信号通路上。结论网络药理学证实了JWSTP多成分、多靶点、多途径的作用特点,预测了其用于SA治疗的可能作用机制,为作用机制和活性成分的研究提供基础。

Objective To screen the main active ingredients of Jianwei Shoutai Pills(JWSTP) based on the network pharmacology technology, predict the targets of the active ingredients and discuss mechanisms of JWSTP in the treatment of spontaneous abortion(SA). Methods The active ingredients and targets in JWSTP were screened on traditional Chinese medicine system pharmacology database and analysis platform. Disease targets of SA were screened and potential targets of JWSTP in the treatment of SA were predicted with GeneCards and OMIM database. The protein-protein interaction of potential targets were constructed on STRING online platform. The gene ontology analysis in biological processes and Kyoto Encyclopedia of Genes and Genomes pathways were enriched by DAVID 6.8 online platform to obtain key pathways, and to construct a network of active ingredients and potential targets and key pathways. Results A total of 18 active ingredients were obtained from JWSTP, and 108 possible targets for the treatment of SA were obtained. The key targets included transcription factor AP-1, tumor necrosis factor, protein kinase AKT1, IL-6, vascular endothelial growth factor A, mitogen-activated protein kinase 1, and so on. The key targets were mainly enriched in biological processes such as positive regulation of transcription from RNA polymerase Ⅱ promoter,apoptosis and inflammatory response, and they are mainly concentrated in PI3 K-Akt, mitogen-activated protein kinase, and tumor necrosis factor and other signaling pathways. Conclusion The multi-components, multi-targets and multi-pathways action characteristics of JWSTP were confirmed by network pharmacology technology, and the possible mechanisms of JWSTP in the treatment of SA provided theoretical basis to its mechanisms and active ingredients in further study.