摘要
目的采用网络药理学和分子对接技术探讨黄连治疗乙型肝炎、非酒精性脂肪肝的分子机制,为细胞实验和动物实验提供参考。方法依据中药系统药理学数据库和分析平台(TCMSP)筛选黄连有效化学成分,借助毒性与基因比较数据库(CTD)、TCMSP和Uniport数据库筛选活性成分潜在靶标。通过可视化和集成发现的数据库(DAVID)生物信息学资源进行通路富集分析,采用Rstudio的ggplot2绘制通路图;通过SYBYL2.1软件分析黄连活性成分与关键靶点相互作用;借助Ligplot软件计算黄连活性最好的化学成分与关键靶点相互作用的氢键、疏水作用。结果筛选出黄连有效活性成分8个,筛选出潜在靶标84个,涉及代谢途径83条,包括乙型肝炎(P-Value=3.5E-19)和非酒精性脂肪肝(P-Value=9.9E-8)通路。通过分子对接明确穆坪马兜铃酰胺、盐酸巴马汀、槲皮素、(R)-四氢小檗碱是黄连治疗乙型肝炎、非酒精性脂肪肝活性成分;促分裂素原活化蛋白激酶1(MAPK1)、MAPK3可能是黄连治疗乙型肝炎、非酒精性脂肪肝的关键靶标蛋白。活性最好的化学成分穆坪马兜铃酰胺与7个关键靶标蛋白形成16氢键、63个氨基酸位点。结论初步筛选出黄连治疗乙型肝炎、非酒精性脂肪肝的活性成分及分子机制,可为黄连保肝活性成分的开发提供理论依据。
Objective To study the molecular mechanism of Huanglian(Coptis chinensis Franch) in prevention and treatment of hepatitis B and non-alcoholic fat liver disease based on molecular docking analysis and network pharmacology technology,and to provide a reference for clinical application. Methods Based on Traditional Chinese Medicine Systems Pharmacology(TCMSP) database,effective chemical composition of Huanglian were retrieved.Rat acute toxicity,AMES toxicity and Carcinogens of effective chemical composition were predicted by admet SAR.Retrieval of therapeutic targets of effective chemical composition based on CTD, TCMSP,Drug Bank and Uniprot.The potential targets were analyzed by DAVID and use Rstudio ggplot2 software to establish network model.Docking of effective chemical composition and rheumatoid targets base on sybyl. Results Eight effective chemical composition of Huanglian.Toxicity prediction shows high safety of Huanglian.Collection of 84 potential targets and 83 metabolic pathways.Including access hepatitis B(P-value=3.5 E-19) and non-alcoholic fatty liver disease(P-Value=9.9 E-8). Moupinamide,palmatine,(R)-canadine and quercetin play an important role in hepatitis B and non-alcoholic fatty liver disease.MAPK1 and MAPK3 were the key target proteins in the treatment of hepatitis B and non-alcoholic fatty liver disease.Moupinamide activity was best associated with the formation of 16 hydrogen bonds and 63 amino acid sites with 7 key target proteins. Conclusion The active ingredients and molecular mechanism of non-alcoholic fatty liver disease and Hepatitis B with Huanglian,it provides a theoretical basis for the clinical application of active ingredients in Huanglian.
作者
杨欣
李亚辉
沙宗阁
李尧锋
杨长福
YANG Xin;LI Yahui;SHA Zongge;LI Yaofeng;YANG Changfu(College of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)
出处
《医药导报》
CAS
北大核心
2020年第3期275-280,共6页
Herald of Medicine
基金
贵州省科技计划项目(黔科合平台人才[2017]5735号-11)
贵州省教育厅青年科技人才成长项目(黔教合KY字[2018]211)
贵州省科技计划项目(黔科合基础[2019]1028号)。
关键词
黄连
化学成分
乙型肝炎
脂肪肝
非酒精性
分子对接
网络药理学
Coptis chinensis Franch
Chemical composition
Hepatitis B
Fatty liver disease,non-alcoholic
Molecular function
Network pharmacology
