基于整合药理学探究复幼合剂治疗性早熟的“中药-化学成分-关键靶标-通路”

Study on the“traditional Chinese medicine-chemical component-target-pathway”of Fuyou mixture in the treatment of precocious puberty based on integrated pharmacology

目的基于整合药理学策略,分析我院院内制剂复幼合剂治疗性早熟的中药物质基础以及作用机制。方法用中药整合药理学思路和方法预测复幼合剂治疗性早熟的中药主要活性成分以及疾病作用靶标,并对候选关键靶标进行富集分析,从细胞定位、蛋白、基因功能等方面探索其治疗性早熟的可能作用机制。结果筛选出复幼合剂治疗性早熟的候选关键靶标116个,选取Degree值前100位的候选关键靶标进行基因本体论(GO)和京都基因与基因组(KEGG)富集分析,获得候选关键靶标的GO分析结果5835条,KEGG通路富集分析结果215条,筛选出雌激素受体α(ESR1)、雌激素受体β(ESR2)、胰岛素样生长因子1(IGF1)及其受体(IGF1R)、卵泡刺激素受体(FSHR)、瘦素(LEP)及其受体(LEPR)、黄体生成素受体(LHCGR)等关键靶标,定位在生物调节、细胞进程等基因功能和雌激素信号通路、促性腺激素释放激素信号通路、甲状腺激素信号通路等信号通路方面。结论复幼合剂主要作用于ESR1、ESR2、IGF1以及LEP等靶点,通过雌激素信号通路等参与调控性早熟的疾病发生和发展过程,从而发挥治疗作用。

Objective To analyze the material basis and molecular mechanism of Fuyou(FY)mixture for the treatment of precocious puberty based on integrated pharmacological strategies.Methods The main active components and targets of FY mixture for the treatment of precocious puberty were predicted by using the integrated pharmacology strategy of traditional Chinese medicine and the key targets were screened for enrichment analysis,in order to explore the possible mechanism in treating precocious puberty from the cellular localization,protein and gene function.Results A total of 116 candidate key targets for the treatment of precocious puberty with FY mixture were selected.The top 100 key targets were analyzed for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG),as a result,5835 GO analysis results and 215 KEGG pathway enrichment analysis results were obtained.The key targets of estrogen receptorα(ESR1),estrogen receptorβ(ESR2),insulin-like growth factor 1(IGF1)and its receptor(IGF1R),follicle stimulating hormone receptor(FSHR)leptin(LEP)and its receptor(LEPR),luteinizing hormone receptor(LHCGR)were screened out.It is targeted at the functions of genes such as biological regulation and cellular process as well as signaling pathways such as estrogen signaling pathway,GnRH signaling pathway and Thyroid hormone signaling pathway.Conclusion FY mixture mainly acts on the targets of ESR1,ESR2,IGF1 and LEP,and participates in the regulation of the occurrence and development of precocious puberty through multiple pathways,so as to play a certain therapeutic role.