中国中药杂志

2021, v.46(12) 3016-3023

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基于网络药理学的吴茱萸治疗失眠的潜在靶点分析
Potential targets of Euodiae Fructus in treatment of insomnia based on network pharmacology

李磊;卢静静;王伟涛;王娜;王理想;马艳敏;刘姝;
LI Lei;LU Jing-jing;WANG Wei-tao;WANG Na;WANG Li-xiang;MA Yan-min;LIU Shu;the First Affiliated Hospital of Henan University of Chinese Medicine;Henan University of Chinese Medicine;

摘要(Abstract):

吴茱萸涌泉穴位贴敷能够改善失眠患者的睡眠质量,而小檗碱是其发挥疗效的主要有效化合物。该研究通过中药系统药理学数据库及分析平台(TCMSP)筛选出19个活性成分,203个药物靶点,经与GeneCards和在线人类孟德尔遗传(OMIM)综合数据库比对,获得24个疾病与药物的交集基因,利用STRING 11.0软件构建吴茱萸治疗慢性失眠的蛋白互作网络,马修斯相关系数算法筛选核心基因,并对关键基因进行基因本体富集分析和京都基因与基因组百科全书通路富集分析。结果显示,吴茱萸中的小檗碱、吴茱萸次碱等主要化合物,通过调节C-反应蛋白(CRP)、雌激素受体1(ESR1)、5-羟色胺受体(5-HT)及白细胞介素6(IL-6)等关键基因,参与神经递质受体活性等生物过程,从而发挥镇静安神、抗焦虑抑郁的作用。基于网络分析结果,将60只SPF级4周龄小鼠随机分为空白组、模型组、地西泮片组以及小檗碱低、中、高剂量组,并给予相应药物治疗7 d。结果显示,小檗碱能显著减少小鼠活动次数和站立次数,以及下调下丘脑组织中CRP和IL-6基因的表达,上调5-HT的表达(P<0.01),而对ESR1没有明显影响。该研究构建了吴茱萸治疗慢性失眠的调控网络,并通过实验验证,揭示了吴茱萸参与神经递质受体活性等多个生物过程,从而发挥治疗失眠的机制,为其临床应用提供了一定的参考依据。
The acupoint application of Euodiae Fructus at Yongquan(KI1) can significantly improve the sleep quality of patients with insomnia with berberine as the main effective component for the efficacy. Nineteen active compounds and 203 drug targets were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). After comparison with GeneCards and Online Mendelian Inheritance in Man(OMIM), 24 common genes of diseases and drugs were obtained. STRING 11.0 was used to construct a protein-protein interaction(PPI) network of the overlapping genes, and Matthews correlation coefficient(MCC) was employed to screen the core genes, which were then subjected to enrichment analysis with gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG). The results revealed that the main compounds of Euodiae Fructus, such as berberine and rutaecarpine, participated in the biological processes(such as neurotransmitter receptor activity) by regulating C-reactive protein(CRP), estrogen receptor 1(ESR1), 5-hydroxytryptamine(5-HT) receptor, and interleukin-6(IL-6) to exert sedative, anxiolytic, and antidepressant effects. Sixty 4-week-old SPF mice were randomly divided into a control group, a model group, a positive drug(diazepam tablets) group, and low-, medium-, and high-dose berberine groups. Medication with corresponding drugs was performed for one week. The results demonstrated that berberine was potent in reducing the activities and standing times of mice, down-regulating the levels of CRP and IL-6 mRNA in the hypothalamus, and up-regulating the expression of 5-HT(P<0.01); however, no significant effect on ESR1 was observed. The network of Euodiae Fructus in treating insomnia was constructed by network pharmacology and verified by tests. The findings indicated that the therapeutic efficacy of Euodiae Fructus in treating insomnia was achieved by participating in multiple biological processes, such as neurotransmitter receptor activity, which provided a scientific basis for its clinical application.

关键词(KeyWords): 网络药理学;吴茱萸;小檗碱;失眠
network pharmacology;Euodiae Fructus;berberine;insomnia

Abstract:

Keywords:

基金项目(Foundation): 河南省中医药科学研究专项(20-21ZY2048)

作者(Authors): 李磊;卢静静;王伟涛;王娜;王理想;马艳敏;刘姝;
LI Lei;LU Jing-jing;WANG Wei-tao;WANG Na;WANG Li-xiang;MA Yan-min;LIU Shu;the First Affiliated Hospital of Henan University of Chinese Medicine;Henan University of Chinese Medicine;

DOI: 10.19540/j.cnki.cjcmm.20210419.401

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