基于网络药理及分子对接技术探讨贯叶金丝桃-川芎治疗焦虑症的作用机制  

Mechanism of Hyperici Perforati Herba-Chuanxiong Rhizoma in the Treatment of Anxiety Disorder Based on Network Pharmacology and Molecular Docking

作　　者：张继伟[1] 李秋艳[1] 张蕊[1] 顾继昱 倪恬 张雪雪 唐威 ZHANG Ji-wei;LI Qiu-yan;ZHANG Rui;GU Ji-yu;NI Tian;ZHANG Xue-xue;TANG Wei(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091)

机构地区：[1]中国中医科学院西苑医院,北京100091

出　　处：《世界中西医结合杂志》2023年第1期85-92,共8页World Journal of Integrated Traditional and Western Medicine

基　　金：国家中医药管理局第三届国医大师传承工作室及全国名中医传承工作室建设项目;中国中医科学院科技创新工程项目(CI2021A05012)。

摘　　要：目的应用网络药理学及分子对接方法探讨贯叶金丝桃-川芎药对治疗焦虑症作用机制,为临床应用贯叶金丝桃-川芎药对提供依据。方法利用TCMSP数据库进行化合物成分检索,Swiss Target Prediction数据库预测药物靶点,在Uniprot数据库进行标准化处理。使用OMIM数据库、Disgenet数据库、Genecards数据库获焦虑症相关靶点数据。利用Venny 2.1在线软件绘制韦恩图,Cytoscape 3.7.2软件构建“药物-成分-靶点-疾病”可视化网络图。使用Network Analyzer软件对网络图进行拓扑分析,利用DAVID 6.8数据库,基于R3.6.1软件使用Bioconductor生物信息软件包,进行关键靶基因GO与KEGG功能富集分析。对接程序由AutoDock-Vina 1.1.2执行,应用PyMOL 2.3.0和BIOVIA Discovery Studio 2016软件对结果可视化。结果共筛选出贯叶金丝桃-川芎药对12个活性成分,潜在靶点413个,焦虑症相关靶点1871个,活性成分-疾病共同靶点119个,进行拓扑分析得到9个核心成分。对其PPI网络进行MCODE聚类分析共得到4个基因簇和3个核心基因。GO和KEGG分析显示,贯叶金丝桃-川芎药对治疗焦虑症主要涉及化学突触传递调节、神经活性配体-受体相互作用、含5-HT的神经突触、多巴胺(Dopamine,DA)能神经突触等信号通路相关。筛选出4种成分与关键靶点结合强度较强,且具有保护神经细胞、调节神经递质、抗氧化等作用的核心活性成分。结论贯叶金丝桃-川芎药对可能与5-HT、GABA、DA神经递质信号通路调节关系密切,并通过减轻氧化应激、抑制自噬、保护及促进神经细胞再生等机制治疗焦虑症。Objective To explore the mechanism of Hyperici Perforati Herba(HPH)-Chuanxiong Rhizoma(CR)in the treatment of anxiety disorder based on network pharmacology and molecular docking to provide references for the clinical application of HPH-CR drug pair.Methods TCMSP was used for component retrieval,Swiss Target Prediction was used to predict drug targets,and Uniprot was used for standardization.OMIM,Disgenet,and Genecards were used to obtain the data on anxiety-related targets.Venn diagram was plotted by Venny 2.1.Cytoscape 3.7.2 was used to construct the"drug-component-target-disease"visualized network.Network Analyzer was adopted for topological analysis of the network.DAVID 6.8 and Bioconductor software package based on R3.6.1 software were used for GO and KEGG enrichment analyses of key target genes.The docking procedure was performed by AutoDock-Vina 1.1.2 and the results were visualized using PyMOL 2.3.0 and BIOVIA Discovery Studio 2016.Results Twelve active components of the HPH-CR drug pair,413 potential targets,and 1871 anxiety-related targets were screened out.There were 119 common targets of active components and the disease,and nine core components were obtained by topological analysis.Four gene clusters and three core genes were obtained by MCODE clustering analysis of the PPI network.GO and KEGG analysis revealed that in the treatment of anxiety disorder,the HPH-CR drug pair was primarily involved in signaling pathways such as chemical synaptic transmission regulation,neuroactive ligand-receptor interaction,synapses containing 5-HT,and dopaminergic synapses.Four core active components were screened,which had strong binding affinity with key targets,and had the functions of protecting nerve cells,regulating neurotransmitters,and resisting oxidation.Conclusion HPH-CRdrug pair may be closely related to the regulation of 5-HT,GABA,and DA neurotransmitter signaling pathways and can treat anxiety disorder by reducing oxidative stress,inhibiting autophagy,and protecting and promoting nerve cell regeneration.

关 键 词：贯叶金丝桃 川芎 焦虑症 网络药理学 分子对接 

分 类 号：R285.6[医药卫生—中药学]