分子对接技术结合网络药理学研究增液承气汤加减治疗慢性传输型便秘作用机制

Study of the Mechanism of Zengye Chengqi Decoction Modified(增液承气汤加减)in the Treatment of Slow Transit Constipation by Molecular Docking Technique Combined with Network Pharmacology

目的基于网络药理学及分子对接技术探讨增液承气汤加减治疗慢性传输型便秘的作用机制。方法利用TCMSP及BATMAN-TCM数据库平台筛选方中药物化合物及作用靶点;利用OMIM、GeneCard数据库搜索慢性传输型便秘疾病相关靶点,取其与增液承气汤加减中化合物的作用靶点交集得到增液承气汤加减治疗慢性传输型便秘的潜在作用靶点。运用Cytoscape软件建立并分析有效化合物-作用靶点网络;利用STRING数据库平台分析作用靶点蛋白质相互作用(PPI)网络;利用Bioconductor软件包对作用靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析;利用AutoDock Vinna模块将处方中核心化合物及核心靶点进行分子对接,以探索增液承气汤加减治疗慢性传输型便秘的作用机制。结果筛选得到增液承气汤加减50个潜在的药效成分,协同作用于MAPK1、ANXA1、MAPK3、C3、CHRM2、AKT1、JUN、RXRA、EDN1等354个靶点发挥治疗慢性传输型便秘的功效。分子对接结果显示,关键活性成分与核心靶点均能自发结合。结论研究从网络药理学的角度揭示了增液承气汤加减治疗慢性传输型便秘的潜在药效成分、作用靶点及作用机制,为增液承气汤加减临床用于慢性传输型便秘的治疗及其作用机制研究提供参考。

Objective To explore the mechanism of Zengye Chengqi Decoction Modified(增液承气汤加减)in the treatment of slow transit constipation based on network pharmacology and molecular docking technology.Methods TCMSP and BATMAN-TCM database platform were used to screen drug compounds and action targets.OMIM and GeneCard databases were used to search for targets related to slow transit constipation,and the potential targets of Zengye Chengqi Decoction Modified for the treatment of slow transit constipation were obtained by the intersection of the targets and the compounds in Zengye Chengqi Decoction Modified.Cytoscape software was used to establish and analyze the effective compound target network.Using STRING database platform to analyze PPI network of action target;Bioconductor software package was used to analyze the GO function and KEGG pathway enrichment of the target.AutoDock Vinna module was used to conduct molecular docking of the core compounds and core targets in the prescription,so as to explore the mechanism of Zengye Chengqi Decoction Modified for the treatment of slow transit constipation.Results Fifty potential pharmacodynamic components of Zengye Chengqi Decoction Modified were screened,which synergically acted on 354 targets including MAPK1,ANXA1,MAPK3,C3,CHRM2,AKT1,JUN,RXRA and EDN1 in the treatment of chronic transit constipation.The molecular docking results showed that the key active ingredients and the core target could spontaneously bind.Conclusion From the perspective of network pharmacology,this study revealed the potential pharmacodynamic components,action targets and action mechanism of Zengye Chengqi Decoction Modified in the treatment of slow transit constipation,providing reference for the clinical application of Zengye Chengqi Decoction Modified in the treatment of slow transit constipation and the study of its action mechanism.