摘要
目的采用网络药理学和分子对接探讨及验证“柴胡-白芍”药对治疗代谢相关脂肪性肝病(MAFLD)的主要物质基础及作用机制。方法通过中药系统药理学分析平台(TCMSP)和Swiss Target Prediction在线网站收集柴胡、白芍的活性成分和治疗靶点;在Therapeutic Target Database、Drugbank、DisGeNET数据库中获取MAFLD的疾病靶点并构建韦恩图,筛选中药与疾病的交集靶点;利用Cytoscape 3.9.0软件绘制“中药-活性成分-疾病-交集靶点”网络并进行网络拓扑分析,筛选“柴胡-白芍”药对治疗代谢相关脂肪性肝病的核心成分;借助STRING数据库获取交集靶点蛋白-蛋白相互作用(PPI)网络参数,借助Cytoscape 3.9.0构建PPI网络并进行网络拓扑分析,筛选核心靶点。采用Metascape平台分析“中药-疾病”交集靶点参与的生物过程及信号通路,使用微生信平台将结果绘制成柱状图和气泡图进行可视化,绘制“中药-核心成分-核心靶点-生物功能-信号通路”网络,可视化“柴胡-白芍”药对治疗MAFLD的主要作用机制。采用分子对接技术验证核心成分与核心靶点的相互作用。结果筛选得到柴胡-白芍活性成分29个,治疗靶点292个,其中涉及MAFLD的靶点有138个。根据网络拓扑分析共筛选得到10个核心成分,如槲皮素、山柰酚、异鼠李素、β-谷甾醇、豆甾醇等,筛选得到23个核心靶点,如IL6、TNF、AKT1、TP53、IL1B等。GO Molecular Functions富集结果157个,Biological Processes富集结果1767个,Cellular Components富集结果71个,KEGG通路富集结果209条,主要涉及MAPK信号通路、NF-κB信号通路、坏死性凋亡等。结论“柴胡-白芍”药对治疗代谢相关脂肪性肝病具有多成分、多靶点、多途径的整体调节特点,为深入药理研究和临床应用提供具体依据。
Objective To explore the mechanism of the“Chaihu(Radix Bupleuri)-Baishao(Paeoniae Radix Alba)”in the treatment of metabolic associated fatty liver disease(MAFLD)by network pharmacology and molecular docking.Methods The active ingredients and therapeutic targets of“Chaihu(Radix Bupleuri)-Baishao(Paeoniae Radix Alba)”were collected through the Traditional Chinese Medicines Systems Pharmacology Platform(TCMSP)and the Swiss Target Prediction online website.The disease targets of MAFLD were obtained in the Therapeutic Target Database,Drugbank and DisGeNET databases,and the Venn diagram was constructed to screen the intersection targets of traditional Chinese medicine and disease.Cytoscape 3.9.0 software was used to map the“Chinese Medicine-Active Ingredient-Disease-Intersection Target”network and perform network topology analysis to screen the core components of“Chaihu(Radix Bupleuri)-Baishao(Paeoniae Radix Alba)”.The protein-protein interaction network between the intersecting targets was mapped by using the STRING database and Cytoscape 3.9.0 software,and the key targets were selected based on the network topology analysis parameters.The Metascape platform was used to analyze the biological processes and signaling pathways involved in the intersection targets of“TCM-disease”,and the results were visualized as histograms and bubble charts using the Bioinformatics platform.Mapping the network of“Chinese Medicine-Core Ingredients-Core Targets-Biological Functions-Signaling Pathways”to visualize the main mechanism of“Chaihu(Radix Bupleuri)-Baishao(Paeoniae Radix Alba)”in the treatment of MAFLD.Molecular docking techniques were used to verify the interaction between core components and core targets.Results A total of 29 active ingredients of Chinese medicine and 292 therapeutic targets were screened out,138 of which involved MAFLD.Ten core Ingredients such as quercetin,kaempferol,isorhamnetin,beta-sitosterol and Stigmasterol and 23 core targets such as interleukin-6(IL-6),tumor necrosis factor(TNF),AKT1,tumor protein p53(TP53)and Interleukin 1 B(IL-1 B)were obtained by network topology analysis.There were 157 enrichment results by GO molecular functions,1767 enrichment results by biological processes,71 enrichment results by cell components and 209 enrichment results by KEGG pathway,which were mainly related to MAPK signal path,NF-κB signal path,Necroptosis,etc.Conclusion The pair of“Chaihu(Radix Bupleuri)-Baishao(Paeoniae Radix Alba)”has the overall regulation characteristics of multi-component,multi-target and multi-pathway in the treatment of MAFLD,providing a specific basis for in-depth pharmacological research and clinical application.
作者
严海艺
郭瑞
YAN Haiyi;GUO Rui(China Academy of Chinese Medical Sciences,Beijing 100029,China)
出处
《辽宁中医杂志》
CAS
2022年第5期1-6,221-222,共8页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81673967)
中国中医科学院科技创新工程(CI2021A00805)
关键词
柴胡
白芍
代谢相关脂肪性肝病
网络药理学
分子对接
Chaihu(Radix Bupleuri)
Baishao(Paeoniae Radix Alba)
metabolic associated fatty liver disease
network pharmacology
molecular docking
作者简介
严海艺(1991-),女,四川雅安人,医师,博士研究生,研究方向:肝胆疾病的中医药防治;通讯作者:郭瑞(1993-),女,山东菏泽人,医师,硕士,研究方向:中医内科学。
