基于网络药理学和分子对接技术探究大承气汤治疗便秘作用机制

Investigating the Mechanism of Action of Dachengqi Decoction in the Treatment of Constipation Based on Network Pharmacology and Molecular Docking Technology

摘要: 目的：运用网络药理和分子对接技术探究大承气汤治疗便秘的有效成分、作用靶点、信号通路及分子机制。方法：运用TCMSP数据库遴选大承气汤中的有效成分、作用靶点；通过GeneCards、OMIM、TTD、DrugBank数据库以“constipation”为检索词进行搜集得到便秘相关靶点；利用Cytoscape 3.10.0软件构建“药物成分–潜在作用靶点”网络关系图；再导入String数据库生成靶点蛋白质互作关系图。本研究采用Metascape对核心作用靶点开展功能标注分析，即基因本体及京都基因与基因组百科全书通路富集分析。同时，运用Autodock分子对接技术模拟配体–受体相互作用，从分子层面验证活性成分与关键靶蛋白的结合稳定性与亲和力。结果：获得大承气汤治疗便秘的相关活性成分有木犀草素、柚皮素、β-谷甾醇、川陈皮素等。核心靶点有RAC-alpha serine/threonine-protein kinase (RAC-α丝氨酸/苏氨酸蛋白激酶)、Cellular tumor antigen p53 (肿瘤蛋白p53)、Tumor necrosis factor (肿瘤坏死因子)、Epidermal growth factor receptor(表皮生长因子受体)、Interleukin-6 (白细胞介素-6)等。GO富集分析共得生物学过程(BP) 323条、细胞组成(CC) 101条、分子功能(MF) 144条，KEGG通路有205条。分子对接结果表明，大承气汤有效成分与其作用靶点稳定结合。结论：大承气汤是通过多条通路、多种成分、多个靶点治疗便秘。

Abstract: Objective: Investigating the active ingredients, targets, signalling pathways and molecular mechanisms of Dachengqi Decoction for the curing of constipation by using network pharmacology and molecular docking. Methods: The TCMSP database was utilised to select the main effective Chinese medicines and targets in Dachengqi Decoction for the treatment of constipation; GeneCards, OMIM, TTD, and DrugBank databases were used to obtain constipation-related targets by using the search term “constipation”; Cytoscape 3.10.0 database was used to construct a network diagram of “drug components-potential targets”, and then imported into the String database to generate a network diagram of target-protein interfaces. In this study, the Metascape bioinformatics system was used to annotate the core targets, comprising gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Meanwhile, Autodock molecular docking technology was applied to simulate ligand-receptor interactions to verify the binding stability and affinity of the active ingredient with key target proteins at the molecular level. Results: Some relevant active ingredients of Dachengqi Decoction for the treatment of constipation were obtained, including lignans, naringenin, β-sitosterol, and chuan chenpianin. The core targets were RAC-alpha serine/threonine-protein kinase (RAC-alpha serine/threonine-protein kinase), Cellular tumor antigen p53 (tumour protein p53), and Tumor necrosis factor (TNF), Epidermal growth factor receptor (EGFR), Interleukin-6 (Ileukin-6), etc. The GO enrichment analysis yielded a total of 323 biological processes (BP), 101 cellular components (CC), 144 molecular functions (MF), and 205 KEGG pathways. The findings of molecular docking showed that the active ingredients of Dachengqi Decoction were stably bound to their targets. Conclusion: Dachengqi Decoction treats constipation through multiple multiple pathways, multiple composition and multiple targets.