桂枝茯苓丸“异病同治”甲状腺结节、乳腺结节及子宫肌瘤网络药理学机制研究

目的采用网络药理学及分子对接方法探究桂枝茯苓丸治疗足厥阴肝经疾病甲状腺结节、乳腺结节及子宫肌瘤的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)和SwissTargetPrediction数据库检索桂枝茯苓丸组方药物的化学成分并获取靶点,通过GeneCards、OMIM数据库查询疾病相关靶点,获得二者交集靶点基因。采用Cytoscape3.7.2软件构建药物-成分-疾病-靶点网络和蛋白相互作用网络,利用R语言对靶点进行GO富集分析和KEGG通路富集分析,运用PyMOL软件进行分子对接。结果共筛选出桂枝茯苓丸活性成分116个,对应有效靶点1109个,与3种疾病的交集靶点79个。对交集靶点富集分析发现,桂枝茯苓丸治疗甲状腺结节、乳腺结节及子宫肌瘤的共同关键通路为AGE-RAGE信号通路、MAPK信号通路及PI3K-Akt信号通路。根据KEGG通路富集分析结果确定7个核心靶点(TP53、CCND1、EGFR、SRC、ESR1、VEGFA、GAPDH)。结论桂枝茯苓丸可能通过调控AGE-RAGE信号通路、MAPK信号通路及PI3K-Akt信号通路,作用于TP53、CCND1、EGFR、SRC、ESR1、VEGFA、GAPDH等靶点,发挥活血、化瘀、消癥功效,可为桂枝茯苓丸“异病同治”机制研究提供参考。

Study on Network Pharmacological Mechanism of Guizhi Fuling Pills in Treating Thyroid Nodule,Breast Nodule and Hysteromyoma

Objective To explore the mechanism of Guizhi Fuling Pills in treating the diseases of Foot-Jueyin Liver Meridian:thyroid nodule,breast nodule and hysteromyoma by network pharmacology and molecular docking.Methods The chemical components of Guizhi Fuling Pills were searched through TCMSP and SwissTargetPrediction database and the targets were obtained.Disease-related targets were searched through GeneCards and OMIM databases,and the intersection target genes of the two were obtained.Cytoscape 3.7.2 software was used to construct the protein interaction network and the drug-component-disease-target network.GO enrichment analysis and KEGG pathway enrichment analysis of the targets were performed using the R language.Molecular docking was performed using PyMOL software.Results A total of 116 active components of Guizhi Fuling Pills and 1109 effective targets were screened,and 79 targets were obtained by intersection with the three diseases.Enrichment analysis on intersection targets finds that the common key pathways of Guizhi Fuling Pills on thyroid nodule,breast nodule and hysteromyoma are AGE-RAGE signaling pathway,MAPK signaling pathway and PI3K-Akt signaling pathway.7 core targets(TP53,CCND1,EGFR,SRC,ESR1,VEGFA and GAPDH)were determined according to the KEGG enrichment results.Conclusion Guizhi Fuling Pills may play a role in promoting blood circulation and removing blood stasis and eliminating the accumulation of lumps by regulating AGE-RAGE signaling pathway,MAPK signaling pathway and PI3K-Akt signaling pathway,acting on TP53,CCND1,EGFR,SRC,ESR1,VEGFA,GAPDH and other targets.This study provides references for the mechanism of Guizhi Fuling Pills“treating different diseases with the same method”.