摘要
目的:采用网络药理学方法探讨厚朴抗抑郁的物质基础及作用机制。方法:通过中国知网,Sci Finder,中药系统药理学数据库和分析平台(TCMSP)等数据库收集厚朴药材的主要化学成分;通过BATMAN-TCM数据库筛选出药物成分潜在作用靶标;基于HPO数据库筛选出抑郁疾病相关靶标;采用String数据库对药物成分潜在靶标与抑郁症靶标进行蛋白质相互作用分析,筛选抗抑郁化学成分及其相关靶点,并通过David数据库对其结果进行功能富集分析。基于以上结果,采用Cytoscape v3. 5. 1软件网络化展现厚朴抗抑郁的"药物靶标-疾病靶标""化学成分-靶标-信号通路"的网络关系图,并通过网络拓扑分析从中筛选出关键靶标并对其进行"成分-靶标蛋白"的分子对接验证,进一步明确关键抗抑郁成分及其靶点。结果:从厚朴收集得到的138种化学成分中筛选得到16个与抑郁症相关的活性成分,涉及74个关键作用靶标;分子对接分析结果表明,与其他成分相比,16种活性成分中的α-衣兰油烯等10种挥发性成分与"药物靶标-疾病靶标"相互作用网络图中的5种关键靶标(degree排名前5)胰岛素受体(INSR),丝裂原活化蛋白激酶1(MAPK1),鸟嘌呤核苷酸结合蛋白α抑制3(GNAI3),磷脂酰肌醇3-激酶受体1(PIK3R1),选择性受体B1(GNB1)均具有较好的结合活性;并且该类成分与目前治疗抑郁症化药的直接靶标毒蕈碱型乙酰胆碱受体M2(CHRM2),5-羟色胺受体(HTR) 2B和HTR2C也均具有较好的亲和活力;通路富集分析结果表明厚朴抗抑郁作用可能通过调节神经营养因子信号通路,MAPK信号通路,钙离子信号通路,神经活性配体-受体相互作用等发挥作用。结论:该研究从网络药理学的角度初步揭示了厚朴抗抑郁的药效物质基础及作用机制,筛选得到16个与抑郁症相关的活性成分,可为抗抑郁药物的开发以及厚朴抗抑郁质量标志物的发现提供参考。
Objective:In this paper,the network pharmacology method was used to explore the material basis and the mechanism of Magnoliae Officinalis Cortex(Houpo)on depressive disorder.Method:Firstly,the main chemical components of Houpo were gathered from CNKI,SciFinder,traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and other databases.Next,the potential targets of the chemical ingredients in Houpo were searched and selected by BATMAN-TCM database.The targets of depressive disorder were collected from HPO database.Then all the targets were entered into the search tool(String database)for the retrieval of protein-protein interactions so as to confirm antidepressant chemistries and their related targets.Furthermore,the functional enrichment analysis was carried out through the David database.Based on these above results,the networks of'drug targets-disease targets'and'compounds-targets-pathways'of Houpo on depressive disorder were built by Cytoscape v3.5.1 software,respectively.Network topology analysis was used to screen the key targets and the corresponding components.Then molecular docking verification of'component-target proteins'was further conducted.Result:A total of 16 active compounds involving in 74 key targets for depressive disorder were selected and confirmed from 138 chemical components of Houpo.Molecular docking analysis showed that compared with other components,ten volatile components in the 16 active compounds had good binding activities with the top 5 key targets[the top 5 of degree value,including insulin receptor(INS),mitogen-activated protein kinase 1(MAPK1),guanine nucleotide binding protein alpha inhibition 3(GNAI3),phosphatidylinositol 3-kinase receptor 1(PIK3 R1)and selective receptor B1(GNB1)]and the 3 direct acting targets of popular drugs for depression(muscarinic acetylcholine receptor M2(CHRM2),5-hydroxytryptamine receptor(HTR)2B and HTR2C)The functional enrichment analysis showed the antidepressant mechanism of Houpo mainly involved neurotrophin signaling pathway,MAPK signaling pathway,calcium signaling pathway and neuroactive ligand-receptor interaction,etc.Conclusion:This study reveals the active ingredients and the mechanism of anti-depression of Houpo based on network pharmacology,a total of 16 key active ingredients related to anti-depression are selected.This paper can provide references for development of antidepressants and the discovery of quality markers of Houpo for anti-depression.
作者
王欢欢
吴宏伟
李欣
张晓
许静
郭非非
张红
范建伟
杨洪军
WANG Huan-huan;WU Hong-wei;LI Xin;ZHANG Xiao;XU Jing;GUO Fei-fei;ZHANG Hong;FAN Jian-wei;YANG Hong-jun(Tianjin University of Traditional Chinese Medicine(TCM),Tianjin 301617,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Institute of Chinese Materia Medica,Shaanxi Academy of TCM,Xi'an 710003,China;State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co.Ltd.,Linyi 276006,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2019年第10期162-169,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家重点基础研究计划(973计划)项目(2015CB554406)
山东省重大科技创新工程--"中医精方"重大科技创新工程项目(2018CXGC1305)
陕西省卫生厅基金项目(2014D1)
关键词
抑郁症
厚朴
网络药理学
物质基础
木脂素类
生物碱类
挥发性成分
depression
Magnoliae Officinalis Cortex
network pharmacology
material basis
lignans
alkaloids
volatile components
作者简介
第一作者:王欢欢,硕士,从事中药药效物质基础及质量控制研究,Tel:010-64032656,E-mail:18222157424@163.com;通信作者:张红,博士,研究员,从事中药药效物质基础研究,Tel:010-64032656,E-mail:zhanghong919919@163.com;通信作者:杨洪军,博士,研究员,从事中药药理及整合药理学研究,Tel:010-64032656,E-mail:hongjun0420@vip.sina.com
