基于网络药理学和分子对接探讨正元胶囊治疗癌因性疲乏的作用机制

To Explore the Mechanism of Zhengyuan Capsule in the Treatment of Cancer-Related Fatigue Based on Network Pharmacology and Molecular Docking

目的:采用网络药理学和分子对接方法,探索正元胶囊治疗癌因性疲乏(cancer-related fatigue,CRF)的作用机理。方法:从TCMSP及HERB数据库采集正元胶囊组方药物的活性成分及靶点,从OMIM数据库、Genecards数据库、TTD数据库收集CRF靶点,二者进行交集筛选出正元胶囊治疗CRF潜在作用靶点,然后绘制“中药-成分-靶点-疾病”网络图并对其关键成分进行分析,构建靶点蛋白-蛋白互作网络、筛选出关键靶点,同时进行GO和KEGG通路富集分析,利用分子对接技术探索关键成分与靶点间的相互作用。结果:正元胶囊治疗CRF的关键成分为槲皮素、山柰酚、木犀草素、7-棕榈酸、五味子酯乙等,涉及的关键靶点包括TNF、STAT3、TP53、AKT1、MYC、VEGFA、EGFR、JUN、PTEN等,其作用机制可能与癌症的通路、PI3K/AKT信号通路、癌症的蛋白聚糖、MAPK信号通路以及病毒感染等信号通路有关。分子对接结果表明,槲皮素与TNF、木犀草素与STAT3的结合能力最强。结论:正元胶囊可通过多靶点、多途径的作用机理治疗CRF,可为今后阐明正元胶囊治疗CRF的深入机制提供思路。

Objective:To explore the mechanism of Zhengyuan capsule in the treatment of cancer-related fatigue(CRF)based on network pharmacology and molecular docking.Methods:The active ingredients and targets of Zhengyuan capsule were collected from TCMSP and HERB databases,and the potential targets of Zhengyuan capsule for CRF treatment were screened after interlacing with the CRF targets collected from OMIM database,Genecards database and TTD database.The TCM-ingredient-target-disease network map was drawn and its key ingredients were analyzed.Gene Ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were also performed to establish the target protein-protein-interaction networks and to screen the key targets.Finally,the interactions between key ingredients and targets was discussed by molecular docking.Results:The key active ingredients of Zhenyuan capsule in the treatment of CRF were quercetin,kaempferol,luteolin,7-Hexadecanoic acid and Gomisin B.The key targets involved were TNF,STAT3,TP53,AKT1,MYC,VEGFA,EGFR,JUN and PTEN.Its mechanism may be related to pathways in cancer,PI3K-AKT signaling pathway,proteoglycans in cancer,MAPK signaling pathway and certain viral infection signaling pathways.The molecular docking results showed that quercetin and TNF had the strongest binding ability,followed by luteolin and STAT3.Conclusion:This study shows the multi-target and multi-pathway mechanism of Zhengyuan capsule in the treatment of CRF,which can provide ideas for elucidating the specific mechanism of Zhengyuan capsule in the treatment of CRF in the future.