基于网络药理学和分子对接探究黄厚止泻滴丸治疗克罗恩病的机制
Mechanism of Huanghou Zhixie Diwan in treatment of Crohn disease based on network pharmacology and molecular docking
苏菡 1武文星 2张亚云 3郭盛2
作者信息
- 1. 南京中医药大学附属常州市中医医院脾胃病科,江苏 常州 213000
- 2. 南京中医药大学中药资源产业化与方剂创新药物国家地方联合工程研究中心/江苏省中药资源产业化过程协同创新中心/江苏省方剂高技术研究重点实验室,江苏南京2100232
- 3. 雷允上药业集团有限公司,江苏 苏州 215003
- 折叠
摘要
[目的]基于网络药理学和分子模拟对接技术探究黄厚止泻滴丸治疗克罗恩病(Crohn's disease,CD)的活性成分和作用机制.[方法]在中国药典收载的中药材质量控制指标成分的基础上,通过中药系统药理学数据库TCMSP,根据口服利用度(OB)≥30％、类药性(DL)≥0.18的筛选原则获取黄厚止泻滴丸的潜在活性成分,借助pubchem等数据库和String平台预测黄厚止泻滴丸活性化合物的所有潜在治疗靶点,利用人类基因数据库Gene-Cards确定黄厚止泻滴丸治疗CD的潜在靶点,经Cytoscape软件将结果可视化,通过网络拓扑算法获得核心化合物和核心靶点;通过String平台构建PPI网络获得黄厚止泻滴丸治疗CD的重要靶点,通过DAVID平台对重要靶点进行基因本体(GO)富集及代谢途径(KEGG)富集分析;根据网络药理学结果,使用Autodock Vina软件进行分子对接,评估核心靶点与核心化合物之间的亲和力.[结果]34个化合物被确定为黄厚止泻滴丸的主要活性成分,其中槲皮素、木香烃内酯、穆坪马兜铃酰胺、黄柏酮、6-姜酚等可能是黄厚止泻滴丸治疗CD的核心化合物;筛选出黄厚止泻滴丸治疗CD的重要靶点27个,核心靶点6个,雌激素受体(ESR1)和表皮生长因子受体(EGFR)可能是主要的核心靶点;GO和KEGG分析表明黄厚止泻滴丸核心靶点的生物功能主要集中在调控NO的合成、炎症反应、免疫反应以及细胞凋亡,而FoxO信号通路、HIF-1信号通路可能为黄厚止泻滴丸治疗CD的关键信号通路.同时,分子对接结果表明ESR1与EGFR均能与核心成分进行良好对接.[结论]初步揭示了黄厚止泻滴丸治疗CD的潜在活性成分和作用机制,为进一步阐明黄厚止泻滴丸治疗CD的物质基础,服务于临床应用提供了参考.
Abstract
[Objective]To explore the active ingredients and mechanism of Huanghou Zhixie Diwan in the treatment of Crohn disease(CD)based on network pharmacology and molecular docking.[Methods]On the basis of the quality control index components of traditional Chinese medicine contained in the Chinese Pharmacopoeia,Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and was applied to obtain the potential active components of Huanghou Zhixie Diwan according to the screening principles of oral availability(OB)≥30％and drug-like property(DL≥0.18,With the help of pubchem database and String platform,all potential therapeutic targets of the active compounds of Huanghou Zhixie Diwan were predicted.The human gene database GeneCards was used to determine the potential target of Huanghou Zhixie Diwan for CD treatment Cytoscape software was used to construct the network of active ingredient-potential target genes,the key ingredients and target genes were selected based on topological parameters;A protein-protein interaction(PPI)network was constructed through the STRING platform and the core targets in the network were predicted,and the enrichment analyses of core targets were completed by DA-VID database;According to the results of network pharmacology,Autodock Vina software was used for molecular docking to evaluate the affinity between the core target and the core compound.[Results]There were 34 major active compounds in Huanghou Zhixie Diwan,quercetin、costunolide、moupinamide、oba-cunone and 6-gingerol may be the main therapeutic CD of Huanghou Zhixie Diwan active ingredients.There were 27 core targets and 6 key targets in the treatment of CD were obtained,Estrogen receptor(ESR1)and epidermal growth factor receptor(EGFR)may be the main core targets;GO and KEGG analysis showed that the biological function of the core target of Huanghou Zhixie Dripping Pill mainly focused on regula-ting the synthesis of NO,inflammatory response,immune response and cell apoptosis,while FoxO signal pathway and HIF-1 signal pathway may be the key signal pathway of Huanghou Zhixie Dripping Pill in treating CD.At the same time,the results of molecular docking showed that both ESR1 and EGFR could well dock with the core components.[Conclusion]It is preliminarily explored the potential active ingredi-ents and possible mechanisms of Huanghou Zhixie Diwan in the treatment of CD,and provides reference for further elucidation of the pharmacological effects of Huanghou Zhixie Diwan against CD,subsequent clini-cal application,and development.
关键词
克罗恩病/黄厚止泻滴丸/网络药理学/作用机制/分子对接Key words
Crohn's disease/Huanghou Zhixie Diwan/network pharmacology/mechanism of action/mo-lecular docking引用本文复制引用
出版年
2024
NETL
NSTL
万方数据