基于网络药理学和分子对接技术探讨十九畏药对“郁金-丁香”抗肝纤维化作用机制  

Mechanism of Radix Curcumae-Flos Caryophylli moutan couple on anti-liver fibrosis based on network pharmacology and molecular docking

作　　者：汪居安 王居义 蔡叶 李幸蓉 吴凌 伊艳敏 檀啸 王继洲 WANG Juan;WANG Juyi;CAI Ye;LI Xingrong;WU Ling;YI Yanmin;TAN Xiao;WANG Jizhou(Department of Hepatobiliary Surgery,the First Affiliated Hospital of University of Science and Technology of China,Hefei,Anhui 241002,China;School of Clinical Medicine,Wannan Medicial College,Wuhu,Anhui 230001,China;College of Chinese Medicine,Anhui University of Chinese Medicine,Hefei,Anhui 230038,China;School of Medicine,Anhui University of Science and Technology,Huainan,Anhui 232001,China)

机构地区：[1]中国科学技术大学附属第一医院肝胆外科,安徽合肥241002 [2]皖南医学院临床医学院,安徽芜湖230001 [3]安徽中医药大学中医学院,安徽合肥230038 [4]安徽理工大学医学院,安徽淮南232001

出　　处：《安徽医药》2023年第6期1083-1087,F0002,I0001,共7页Anhui Medical and Pharmaceutical Journal

基　　金：国家自然科学基金面上项目(82170618);安徽省大学生创新创业训练计划(S201910368025)。

摘　　要：目的 通过网络药理学和分子对接技术探讨郁金-丁香药对抗肝纤维化的作用机制。方法 于2022年1月8日检索中药系统药理学数据平台(TCMSP)获取郁金和丁香的有效活性成分及相关靶点并进行筛选和预测;肝纤维化相关靶点的数据通过NCBI基因数据、OMIM数据库和Genecards数据库获取;运用软件Venny 2.1绘制药物-疾病靶点韦恩图,得到药物抗肝纤维化的作用靶点;运用Cytoscape 3.8.2软件构建药物-活性成分-靶点相互作用网络并分析其拓扑结构;运用String数据库构建蛋白质相互作用(PPI)网络图;利用David和Metascape数据库对关键靶点分别进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析;利用PubChem和RCSBPDB数据库对关键成分和靶点进行分子对接。结果 筛选得到郁金-丁香药活性成分44个,对应作用靶点200个,肝纤维化候选靶点3 951个,药物与疾病交集靶点155个。药物-活性成分-靶点网络和PPI网络分析显示槲皮素、山柰酚、柚皮素、β-谷甾醇等是药对治疗肝纤维化的关键成分,蛋白激酶B1(AKT1)、白细胞介素(IL)-6、IL-1β、牛胱天蛋白酶3(CASP3)等为治疗的核心靶点。155个潜在靶点经GO富集至1 889条生物学过程、44条细胞组分表达和94个分子功能相关的过程中。KEGG通路分析显示与133条通路有关,涉及癌症信号通路、乙型肝炎信号通路、TNF信号通路、Toll样受体信号通路等。分子对接表明关键成分与核心靶点结合良好。结论 从网络药理学角度阐明了郁金-丁香药多成分、多靶点、多途径的整体调节特点,初步揭示了其抗肝纤维化的作用机制,为后续研究提供思路与依据。Objective To explore the mechanism of Radix Curcumae-Flos Caryophylli moutan couple against liver fibrosis(LF)by network pharmacology and molecular docking.Methods On January 8,2022,the effective active ingredients and related targets of Ra⁃dix Curcumae-Flos Caryophylli moutan couple were screened and predicted by searching the TCMSP.Datebase of NCBI,OMIM and Genecards were used to obtain liver fibrosis-related targets.Venny 2.1 software was used to draw the drug-disease venn diagram and obtain the targets of moutan couple against LF.Cytoscape 3.8.2 software was utilized to build a drug-active ingredient-target interaction network and to carry out topological analysis.String database was employed to establish PPI network.The GO and KEGG enrichment were carried out through the David and Metascape database.The molecular docking of drug active ingredient and target was based on PubChem and RCSBPDB database.Results A total of 44 active components with 200 corresponding targets,3951 candidate targets for liver fibrosis and 155 common targets for drugs and disease were acquired.Through the analysis of disease-active component-target network and PPI network,quercetin,kaempferol,sitosterol were the key compounds and the core targets were AKT1,IL-6 IL-1β,CASP3,etc.GO entries included 1889 biological process entries,44 cellular component entries and 94 molecular function entries.There were 133 pathways involving cancer signaling pathway,TNF signaling pathway,Hepatitis B receptor signaling pathway,Toll-like receptor signaling pathway,etc.Molecular docking made clear that key compounds were well combined with core targets.Conclusion The results of this study verify the multi-component,multi-target and multi-pathway regulation characteristics of Radix Curcumae-Flos Caryophylli moutan couple,preliminarily predict mechanisms of Radix Curcumae-Flos Caryophylli moutan couple in the treatment of LF,which provides reference for further research.

关 键 词：肝纤维化 十九畏 郁金 丁香 网络药理学 分子对接 蛋白质相互作用图谱 

分 类 号：R285[医药卫生—中药学]