基于网络药理学和分子对接探讨天王补心丹治疗慢传输型便秘作用机制  

Exploration on the Mechanism of Tianwang Buxin Pills for Slow Transit Constipation Based on Network Pharmacology and Molecular Docking

作　　者：徐鸿彬 钱海华[2] 王雅丽 张丹[2] 曾莉[1] XU Hongbin;QIAN Haihua;WANG Yali;ZHANG Dan;ZENG Li(The First School of Clinical Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China;The Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]南京中医药大学第一临床医学院,江苏南京210023 [2]南京中医药大学附属医院,江苏南京210029

出　　处：《中国中医药图书情报杂志》2023年第4期10-16,共7页Chinese Journal of Library and Information Science for Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82074439)。

摘　　要：目的采用网络药理学和分子对接研究分析天王补心丹治疗慢传输型便秘的作用机制,为开拓临床经典古方名方新用途、新运用提供依据。方法收集天王补心丹组成药物的化学成分并预测其相关作用靶点,通过常见疾病数据库(GeneCards、OMIM、TTD)获取疾病慢传输型便秘的相关靶点。并将获得的天王补心丹活性成分作用靶点与慢传输型便秘疾病靶点取交集,利用STRING数据库建立天王补心丹活性成分-慢性传输型便秘-共同靶点蛋白质相互作用(PPI)网络,并通过Cytoscape3.8.2软件对交集靶点进行度值分析,得出药物作用的关键核心靶点;利用DAVID6.8在线数据库对交集靶点进行基因分类(GO)富集分析和京都基因和基因组百科全书(KEGG)通路分析,并利用在线平台微生信将分析结果可视化,运用Autodock软件对关键作用靶点和活性成分进行分子对接,验证网络分析结果。结果检索预测出天王补心丹138个活性成分,762个潜在作用靶点,与疾病慢传输型便秘相关靶点共111个,活性成分87个。其中以AKT1、ESR1、CASP3、IL6、VEGFA、IL1β等为核心靶点,并推测干预机制可能与参与介导HIF-1、TNF、MAPK等信号通路密切相关。分子对接提示,天王补心丹核心有效成分与核心靶点AKT1、CASP3、IL6结合较好。结论天王补心丹可能通过调节炎症反应、调节新生血管生成、舒张肠道平滑肌及保护肠道屏障等机制参与改善和调节慢性传输型便秘。Objective To explore the mechanism of Tianwang Buxin Pills(TWBXP)in treating slow transit constipation(STC)through network pharmacology and molecular docking;To provide a basis for the new usage of the famous ancient formula in clinical practice.Methods The chemical components of TWBXP were collected and the targets of the components were predicted.Then the relevant targets of STC were obtained by GeneCards,OMIM and TTD databases,and intersected with the targets of the active components of TWBXP.Subsequently,proteinprotein interaction(PPI)network was created by the STRING,and Cytoscape 3.8.2 was used to analyse the intersecting targets to identify core targets.GO and KEGG enrichment analyses were performed on the intersecting targets with DAVID 6.8 database,and the online platform Bioinformatics was used to visualize the analysis results.Autodock software was used to conduct molecular docking of key action targets and active components to verify the network analysis results.Results TWBXP has a total of 138 active components and 762 potential targets,of which 111 targets were related to STC,and 87 active components.AKT1,ESR1,CASP3,IL6,VEGFA and IL1βwere core targets in PPI network,and the mechanism was hypothesized to be involved in mediating the HIF-1,TNF,MAPK signaling pathways.Molecular docking results showed that core active components of TWBXP bound well to the core targets AKT1,CASP3 and IL6.Conclusion TWBXP may participate in improving and regulating slow transit constipation by regulating inflammatory reaction,regulating angiogenesis,relaxing intestinal smooth muscle and protecting intestinal barrier.

关 键 词：天王补心丹 慢传输型便秘 网络药理学 分子对接 活性成分 靶点 

分 类 号：R285[医药卫生—中药学] R256.35[医药卫生—中医学]