基于网络药理学探讨四磨汤治疗慢传输型便秘的作用机制研究

Mechanism of action of Simo decoction in treatment of slow transit constipation based on network pharmacology

目的:运用网络药理学方法探讨四磨汤治疗慢传输型便秘(STC)的机制及作用靶点。方法:通过中药系统药理学数据库与分析平台(TCMSP)及TCMID数据库检索四磨汤四味药物所有的有效化合物成分及筛选对应作用靶点,借助GeneCards数据库、DisGeNET数据库查找STC的疾病靶点,使用Venny 2.1.0在线软件作图工具平台映射药物和疾病的交集靶点,借助STRING数据库及Cytoscape 3.7.2软件构建蛋白质相互作用网络,筛选获得核心作用靶点,构建药物-有效化合物-作用靶点网络,利用R语言的clusterProfiler包进行GO功能及KEGG通路富集分析。结果:利用数据库筛选得到39个四磨汤的有效活性成分和209个作用靶点,与STC发病机制相关的作用靶点161个,经过拓扑分析得到26个关键治疗靶点,筛选出槲皮素、山柰酚、β-谷甾醇、豆甾醇、6,7-二甲氧基-2-(2-苯乙基)色酮5个化合物成分。富集分析得到2323条GO功能条目与168条信号通路。结论:四磨汤能够从多成分、多靶点、多途径发挥抗炎症反应、调节神经活性及磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路等作用,从而改善肠道蠕动功能以治疗STC。

Objective:To investigate the mechanism and action targets of Simo decoction in the treatment of slow transit constipation(STC)based on network pharmacology.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and TCMID database were used to search for the effective constituents of the four herbs in Simo decoction and screen out their corresponding action targets,and GeneCards and DisGeNET databases were used to obtain the disease targets of STC.Venny 2.1.0 online drawing tool was used to obtain the intersecting targets of drugs and disease,and STRING database and Cytoscape 3.7.2 were used to construct a protein-protein interaction network.Core action targets were screened out,a drug-effective compound-action target network was constructed,and cluster Profiler package of R language was used to perform GO and KEGG pathway enrichment analyses.Results:Database screening obtained 39 active components and 209 action targets of Simo decoction,among which 161 were associated with the pathogenesis of STC.Topological analysis obtained 26 key treatment targets,and 5 components were screened out,i.e.,quercetin,kaempferol,beta-sitosterol,stigmasterol,and 6,7-Dimethoxy-2-phenethylchromone.Enrichment analysis obtained 2323 GO terms and 168 signaling pathways.Conclusion:Simo decoction can exert an anti-inflammatory response effect and regulate nerve activity and the phosphatidylinositol 3-kinase/protein kinase B signaling pathway through multiple components,targets,and pathways,thereby improving intestinal peristalsis to treat STC.