基于网络药理学与分子对接探讨六味地黄丸治疗肾阴亏虚型老年性便秘的作用机制

Mechanism of action of Liuwei Dihuang pills in treatment of senile constipation with kidney Yin deficiency:A study based on network pharmacology and molecular docking

目的:运用网络药理学与分子对接技术探究六味地黄丸治疗肾阴亏虚型老年性便秘的作用机制。方法:通过TCMSP、TCMID、SwissTargetPrediction获取药物的活性成分并筛选,在Genecards、OMIM、TTD、DisGeNET数据库检索与该疾病相关的主要靶点;运用韦恩图获取六味地黄丸与老年性便秘的交集靶点。将以上数据通过STRING获得交集靶点的蛋白网络,构建药物-活性成分-靶点及蛋白质-蛋白质相互作用(PPI)网络图,进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,并对药物有效成分和核心靶点进行分子对接验证。结果:共获得58个有效活性成分和675个对应靶点,主要有效成分有槲皮素、羟基芫花素、泽泻醇B等;药物-疾病交集靶点296个,包括丝氨酸/苏氨酸蛋白激酶1 (AKT1)、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)等。GO功能富集共有3175个条目,KEGG通路富集得到215条通路,主要有癌症通路、磷脂酰肌醇3-激酶/苏氨酸蛋白激酶信号通路、癌症中的蛋白聚糖、丝裂原活化蛋白激酶信号通路等。分子对接显示该药物主要有效成分和核心靶点蛋白有较好的结合力。结论:该研究在总体上预测了六味地黄丸治疗肾阴亏虚型老年性便秘的活性成分、靶点和信号通路,表明了其多成分-多靶点-多途径的治疗特点。

Objective:To investigate the mechanism of action of Liuwei Dihuang pills in the treatment of senile constipation with kidney Yin deficiency based on network pharmacology and molecular docking.Methods:TCMSP,TCMID,and SwissTargetPrediction were used to obtain the active components of the drug,and Genecards,OMIM,TTD,and DisGeNET databases were used to identify the main targets associated with the disease.The Venn diagram was used to obtain the intersecting targets of Liuwei Dihuang pills and senile constipation.STRING was used to obtain the protein network of intersecting targets and construct a drug-active component-target network and a protein-protein interaction network,and gene ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed.Molecular docking was performed for the effective constituents of the drug and the core targets.Results:A total of 58 effective constituents and 675 corresponding targets were obtained,and the main effective constituents included quercetin,hydroxygenkwanin,and alisol B.There were 296 drug-disease intersecting targets,including AKT1,TNF,and IL-6.The GO functional enrichment analysis obtained 3175 terms,and the KEGG pathway enrichment analysis obtained 215 pathways,including the cancer pathway,the PI3K/Akt signaling pathway,proteoglycans in cancer,and the mitogen-activated protein kinase signaling pathway.Molecular docking showed good binding activity between the main effective constituents of the drug and the core target proteins.Conclusion:This study predicts the active components,targets,and signaling pathways of Liuwei Dihuang pills in the treatment of senile constipation with kidney Yin deficiency,suggesting that it has the features of multiple components,targets,and pathways in treatment.