基于网络药理学联合分子对接研究六磨汤治疗肿瘤性肠梗阻的作用机制

Exploration on the Mechanism of Liumo Decoction in the Treatment of Tumor Intestinal Obstruction based on Network Pharmacology Combined with Molecular Docking

目的:采用网络药理学联合分子对接的方法,筛选出六磨汤的主要活性化合物,预测六磨汤治疗肿瘤性肠梗阻的潜在作用靶点及信号通路,以探讨其治疗肿瘤性肠梗阻的作用机制。方法:利用中药系统药理学数据库和相关文献记载检索六磨汤中6味药的化学成分和作用靶点;通过GeneCards数据库、OMIM数据库、DrugBank数据库及PharmGKB数据库获取肿瘤性肠梗阻的相关靶标。采用R语对交集靶点进行GO功能富集分析和KEGG通路富集分析。使用Chem Office软件、PyMOL软件、Auto Dock软件对活性成分及核心靶点进行分子对接。结果:中药有效活性化合物52个,包括β-谷甾醇、川陈皮素、芦荟大黄素、槲皮素、柚皮素等,与UniProt数据库对照、去重得到药物靶点25个,疾病靶点6530个。通过Venn图可见与肿瘤性肠梗阻的共同靶点179个,蛋白网络互作关键蛋白涉及TP53、RB1、PRKCB、MAPK3、MYC、MAPK14等。通过GO分析得出2425条生物过程、92条细胞组分、205条分子功能条目(P<0.05),通过KEGG通路富集得出158条信号通路(P<0.05),其中通路主要涉及HIF-1信号通路、PI3K-Akt信号通路、TNF信号通路等。结论:六磨汤的活性化合物主要通过多靶点、多通路治疗肿瘤性肠梗阻,本研究结果可为中医药治疗肿瘤性肠梗阻提供一定的理论基础与科学依据。

Objective To screen out the main active compounds of tumor intestinal obstruction by the combination of network pharmacology and molecular docking,and to predict the potential target and signal pathway of tumor intestinal obstruction in the treatment of tumor ileus,and to explore the mechanism of its treatment.Methods The chemical components and target points of six drugs in tumor intestinal obstruction were retrieved by TCMSP platform and related literature records.The related targets of tumor ileus were obtained by GeneCards database,OMIM database,DrugBank database and PharmGKB database.The R language is used to analyze the aggregation target points by go function enrichment and KEGG pathway.The active components and core targets were docking by Chem Office software,PyMOL software and auto dock software.Results 52 active compounds of traditional Chinese medicine,including beta-sitosterol,nobiletin,aloe-emodin,quercetin and naringenin were used in UniProt database to control and weight the drug target 25 and 6530 disease targets were obtained.There were 179 common targets with tumor ileus in Venn map.The key proteins involved TP53,RB1,PRKCB,MAPK3,MYC,MAPK14 and so on.Through GO analysis,2425 biological processes,92 cell components,205 molecular functions were obtained(P<0.05).158 signal pathways were obtained by KEGG pathway enrichment,among which the pathways mainly involved HIF-1 signaling pathway,PI3K-Akt signaling pathway and TNF signaling pathway etc.Conclusion The mechanism of tumor intestinal obstruction in the treatment of tumor ileus is explored.The active compounds of tumor intestinal obstruction are mainly used to treat tumor ileus by multi-target and multi-channel.The results can provide theoretical basis and scientific basis for the treatment of tumor ileus by traditional Chinese medicine.