基于网络药理学与分子对接方法探析六磨汤治疗便秘的机制研究

Mechanism of Liumo Decoction in the treatment of constipation Based on Network Pharmacology and Molecular Docking

目的:利用网络药理学和分子对接方法探究六磨汤治疗便秘的有效成分、作用靶点和通路信息。方法:依托TCMSP数据库筛选出六磨汤有效化合物及其作用靶标,基于CTD数据库和Genecards数据库检索便秘的相关靶标,将两者进行比对得到六磨汤对便秘的作用靶标,再对作用靶标进行拓扑分析筛选出关键靶点,并利用生物学手段分析关键靶点参与的生物学过程和通路,最后用分子对接方法将化合物和作用靶标进行对接,验证化合物进入体内后能否与靶点稳定结合。结果:利用数据库筛选得到43个六磨汤的有效活性成分和116个作用靶点,与便秘发病机制相关的作用靶点54个,经过拓扑分析得到17个关键治疗靶点,这些作用靶点参与机体的细胞代谢、脂多糖的反应、蛋白的磷酸化、细胞对机械刺激的反应等,富集80条信号通路,包括直肠癌信号通路、PI3K信号通路、CAMP信号通路等。分子对接结果显示六磨汤的有效成分与作用靶点结合性良好。结论:六磨汤具有多成分、多靶点,通过这些活性成分和作用靶点多途径调节肠道收缩节律和肠道功能治疗便秘。

Objective To explore the effective components,targets and pathway information of Liumo Decoction in the treatment of constipation by means of network pharmacology and molecular docking.Methods Based on TCMSP database,the effective compounds and their targets of Liumo Decoction were screened.The constipation related targets were retrieved based on CTD database and Genecards database.The constipation targets of Liumo Decoction were obtained by comparing the two databases.The key targets were screened by topological analysis,and the biological processes and connections of the key targets were analyzed by biological means.Finally,we use molecular docking method to dock the compound with the target to verify whether the compound can stably bind to the target after entering the body.Results 43 active ingredients and 116 targets of Liumo Decoction were screened from the database.54 targets were related to the pathogenesis of constipation.17 key therapeutic targets were obtained by topological analysis.These targets were involved in cell metabolism,lipopolysaccharide response,protein phosphorylation,cell response to mechanical stimulation,and enriched 80 signaling pathways.Including rectal cancer signaling pathway,PI3K signaling pathway,CAMP signaling pathway and so on.Molecular docking results showed that the effective ingredients of Liumo Decoction had good binding with the target.Conclusion Liumo Decoction has many components and targets,which regulate intestinal contraction rhythm and intestinal function to treat constipation.