基于网络药理学和分子对接探讨五仁丸治疗便秘作用机制研究

Investigating the action mechanism of Wuren Wan in treating constipation based on network pharmacology and molecular docking

目的:运用网络药理学和分子对接方法探讨五仁丸治疗便秘的作用机制。方法:借助中药系统药理学数据库与分析平台(TCMSP)筛选五仁丸的有效成分及作用靶点,通过GeneCards、OMIM、TTD、PharmGkb、DrugBank等数据库搜集便秘相关靶点;应用R语言获取化合物与疾病共同靶点,运用Cytoscape 3.8.2构建"化合物-靶点"网络,借助String构建共同靶点蛋白质-蛋白质相互作用网络,筛选发挥治疗作用的关键成分与关键靶点;通过R语言进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,并使用分子技术对结果进行验证。结果:文章预测得到五仁丸治疗便秘的有效成分43个,靶点190个,关键化合物为槲皮素、山奈酚、花生四烯酸、柚皮素、川陈皮素、β-谷甾醇、植物甾醇、左旋千金藤啶碱、β-胡萝卜素、雌酚酮等,关键靶点主要为丝氨酸/苏氨酸蛋白激酶1(AKT Serine/Threonine Kinase 1,AKT1)、肿瘤抑制基因P53(Tumor Suppressor p53,TP53)、血管内皮生长因子A(Vascular Endothelial Growth Factor-A,VEGFA)、半胱氨酸天冬氨酸蛋白酶3(Caspase-3,CASP3)、MYC原癌基因蛋白(Myc Proto-oncogene Protein,MYC)、表皮生长因子(Epidermal Growth Factor,EGF)、丝裂原活化蛋白激酶1(Mitogen-activated Protein Kinase 1,MAPK1)等。GO和KEGG通路富集分析结果显示,五仁丸通过以上关键靶点影响流体剪切应力与动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路、人巨细胞病毒感染、PI3K-Akt信号通路等功能发挥重要作用。结论:本研究对五仁丸治疗便秘的多成分、多靶点、多通路的作用与机制进行初步探讨,为进一步研究及临床应用提供思路。

Objective:To explore the action mechanism of Wuren Wan(五仁丸)in treating constipation based on network pharmacology and molecular docking.Methods:The effective components and targets of Wuren Wan were screened by TCMSP.Constipation related targets were collected from GeneCards,OMIM,TTD,PharmGkb and DrugBank databases.The common targets of compounds and diseases were obtained by R language,and a compounds-diseases network was constructed by Cytoscape 3.8.2.A PPI network of common targets was constructed by String,and the key components and key targets that played a therapeutic role were screened.The GO enrichment analysis and KEGG pathway enrichment analysis was performed by R language,and the results were verified by molecular technology.Results:There were 43 effective components and 190 targets of Wuren Wan in treating constipation.The key compounds were quercetin,kaempferol,arachidonic acid,naringenin,nobiletin,beta-sitosterol,Stigmasterol,l-SPD,beta-carotene,estrone,etc..The key targets were mainly AKT1,TP53,VEGFA,CASP3,MYC,EGF,JUN,MAPK1,PTGS2,MMP9 and so on.The results of GO analysis and KEGG pathway enrichment analysis showed that Wuren Wan played an important role in regulating fluid shear stress and atherosclerosis,the AGE-RAGE signaling pathways in diabetic complications,human cytomegalovirus infection,PI3K-Akt signaling pathway,etc.through acting on the above key targets.Conclusion:In this study,the multi-component,multi-target and multi-channel effects and mechanism of Wuren Wan in treating constipation were preliminarily discussed,in order to provide more ideas for further research and clinical application of Wuren Wan.