基于网络药理学的栀子-川芎药对抗抑郁实验研究  

Experimental Research on the Antidepressant Activity of Gardenia jasminoides Ellis-processed Ligusticum Based on Network Pharmacology

作　　者：李筱楠[1] 雍淇文 张铭 姚文静[2] 王佳豪 冯强 王娜[2] 王俊霞[2] 崔力剑[4] LI Xiaonan;YONG Qiwen;ZHANG Ming;YAO Wenjing;WANG Jiahao;FENG Qiang;WANG Na;WANG Junxia;Cui Lijian(Shijiazhuang Institute of Railway Technology,Shijiazhuang 050000,China;Hebei medical university,Shijiazhuang 050000;Laboratory Medicine,Ningjin Integrative Medicine Hospital,Xingtai 055550;Hebei University of Chinese Medicine,Shijiazhuang 050000)

机构地区：[1]石家庄铁路职业技术学院,石家庄050000 [2]河北医科大学,石家庄050000 [3]宁晋县中西结合医院检验科,河北邢台055550 [4]河北中医学院,石家庄050000

出　　处：《中国比较医学杂志》2020年第5期47-53,共7页Chinese Journal of Comparative Medicine

基　　金：河北省自然科学基金资助项目(H2017206281);河北省高等学校科学技术研究项目(QN2018132);河北省重点研发计划自筹项目(17210329);河北医科大学大学生创新性实验计划(USIP2019122,USIP2019228);河北省中医药管理局项目(2014008)。

摘　　要：目的基于网络药理学研究栀子-川芎药对抗抑郁物质基础及作用机制,并使用ICR(Institute of Cancer Research)小鼠进行栀子-川芎药对抗抑郁物质基础的初步测试。方法通过web of science,CNKI,sciencedirect等数据库,收集栀子-川芎药对治疗抑郁症的活性成分并根据类药性原则进行筛选。使用Swiss Target Prediction database及GeneCards进行栀子-川芎药对抗抑郁作用靶点预测及筛选。通过String数据库对筛选出的靶点进行蛋白相互作用分析,并采用cluego软件对关键抗抑郁作用靶点进行信号通路的富集分析。在此基础上构建栀子-川芎药对抗抑郁活性成分-作用靶点-信号通路网络,并通过Cytoscape 3.7.0软件对其进行拓扑分析。根据分析结果,对栀子-川芎抗抑郁靶标网络中筛选出的排名前四位的化合物进行ICR小鼠抗抑郁活性初步测试。结果基于Cytoscape 3.7.0软件的分析结果,发现栀子-川芎药对抗抑郁的活性成分主要为4-methoxyl-phenethylbutyl ether,jasminoside J,Gardenal-I和丁基苯酞,主要作用靶点为COMT、HTR1A、DRD2、SLC6A4、SLC6A3、MAOA、GRM5、DRD4、DRD3、HTR2A、HTR3A、GRIA1、APP、HTR1B和GRM1等,主要信号通路为Serotonergic synapse和Dopaminergic synapse。动物实验表明,与空白组相比,阳性对照组、丁基苯酞及Gardenal-I中、高剂量组均能显著性减少不动时间,4-methoxyl-phenethyl-butyl ether高剂量组能减少不动时间,进一步验证了丁基苯酞、Gardenal-I,4-methoxyl-phenethyl-butyl ether具有一定的抗抑郁活性,而jasminoside J组未能明显减少不动时间,显示无抗抑郁活性。结论基于网络药理学预测及动物实验初步验证,栀子-川芎药对抗抑郁的物质基础为丁基苯酞、Gardenal-I,4-methoxyl-phenethyl-butyl ether,此实验为进一步研究栀子-川芎药对抗抑郁的作用机制和筛选抗抑郁新药奠定基础。Objective Objective Based on the network pharmacology approach,this paper aimed to study the useful material base and functioning mechanism of Gardenia jasminoides Ellis and Ligusticum for the treatment of depression.Their antidepressant effects were initially tested and verified using ICR(Institute of Cancer Research)mice.Methods Effective compounds of Gardenia jasminoides Ellis and Ligusticum wallichii were collected from the Web of Science,CNKI,and ScienceDirect Databases.Then,the chosen ingredients were further selected or screened according to their generic drug-like principle.The Swiss Target Prediction Database and GeneCards were used to predict and identify the target components with antidepressant activity.Furthermore,the String Database was used to annotate protein interactions,and ClueGO software was used to perform the enrichment analysis of concentrated signal passages for those key functioning targets of the antidepressant activity.Based on the above information,the“ingredient-target-signal-pathway”network was constructed,and its topological analysis was conducted by Cytoscape 3.7.0 software.Based on the result of this analysis,the top 4 compounds were tested for their antidepressant effect in ICR mice.Results Based on Cytoscape 3.7.0 software,the active ingredients with antidepressant effects were 4-methoxyl-phenethyl-butyl ether,jasminoside J,Gardenal-I,and butylphthalide.The main effective targets were COMT,HTR1A,DRD 2,SLC6A4,SLC6A3,MAOA,GRM5,DRD4,DRD3,HTR2A,HTR3A,GRIA1,APP,HTR1B,and GRM1.The main pathways of antidepressants were serotonergic and dopaminergic synapses.Animal experiments showed that the positive control groups,the medium and high dose groups of butylphthalide and Gardenal-I,and the high dose groups of 4-methoxyl-phenethyl-butyl ether could significantly reduce the immobility time compared with the blank groups,which further verified the antidepressant activity of these ingredients.Jasminoside J could not reduce the immobility time,indicating that it did not show an antidepress

关 键 词：网络药理学 抑郁症 栀子 川芎 ICR小鼠 

分 类 号：R-33[医药卫生]