基于网络药理学及分子对接探讨百合知母汤治疗睡眠障碍的活性成分及作用机制

中国医药导刊 ›› 2021, Vol. 23 ›› Issue (8): 574-580.

基于网络药理学及分子对接探讨百合知母汤治疗睡眠障碍的活性成分及作用机制

倪骥杰1，常秋伊2*

1. 上海市闵行区浦江社区卫生服务中心，上海 201112；
2. 上海市浦东新区光明中医医院，上海 201399

收稿日期:2021-05-11 修回日期:2021-07-17 出版日期:2021-08-28 发布日期:2021-08-28
基金资助:
浦江社区卫生服务中心院级科研资助项目(项目编号：2019PW02；项目名称：睡眠养生操联合米粒灸治疗心脾两虚型失眠的临床研究)

Study of Action Mechanism and Active Ingredients of Baihe Zhimu Decoction in the Treatment of Sleep Disorders Based on Network Pharmacology and Molecular Docking

and Molecular Docking

1. Pujiang Community Health Centre of Minhang District， Shanghai 201112， China；
2. Guangming Traditional Chinese Medicine Hospital of Pudong New Area， Shanghai 201399， China

Received:2021-05-11 Revised:2021-07-17 Online:2021-08-28 Published:2021-08-28

摘要/Abstract

摘要： 目的：基于网络药理学与分子对接探讨百合知母汤治疗睡眠障碍的活性成分及作用机制。方法：通过TCMSP数据库获取百合知母汤的有效活性化合物及作用靶点；通过GeneCards、DrugBank数据库获取治疗睡眠障碍的有效作用靶点，利用jvenn及String平台筛选并构建中药及疾病共有靶点基因的蛋白相互作用(PPI)网络；通过Metascape平台对共有基因进行GO及KEGG富集分析。利用Cytoscape软件绘制“中药-活性化合物-靶点”及“中药-活性化合物-共同靶点-通路”网络图，筛选出核心基因。利用TCMNPAS平台进行分子对接。结果：经数据库筛选得到百合知母汤有效活性化合物19个及可能作用靶点121个，作用于睡眠障碍的可能有效靶点66个，其中核心靶点13个。GO富集分析提示百合知母汤作用机制与神经递质水平的调节、细胞对有机环状化合物的应答及神经递质受体活性等相关，KEGG通路分析提示HIF-1、cGMP-PKG、Relaxin信号通路可能为潜在作用通路。分子对接表明核心靶标蛋白与百合知母汤的核心活性成分亲合性较好。结论：百合知母汤可以通过多种活性分子、多靶点、多通路治疗睡眠障碍，为后续研究提供药理学理论基础。

关键词: 百合知母汤, 睡眠障碍, 网络药理学, 作用机制, 信号通路

Abstract: Objective： To explore the active ingredients and mechanism of baihe zhimu decoction in the treatment of sleep disorders based on network pharmacology and molecular docking. Methods： The effective active compounds and targets of baihe zhimu decoction were obtained by TCMSP database. The effective targets of treating sleep disorders were obtained by GeneCards and DrugBank database. The PPI network of common target genes of traditional Chinese medicine and diseases was screened and constructed by jvenn and String. The GO and KEGG enrichment analysis of common genes was carried out by Metascape. The network diagrams of "traditional Chinese medicine-active compound-target" and "traditional Chinese medicine- active compound-common target-pathway" were drawn by using Cytoscape software， and the core genes were screened out. TCMNPAS platform was used for molecular docking. Results： 19 active compounds and 121 potential targets of baihe zhimu decoction were screened by database. 66 potential effective targets of baihe zhimu decoction on sleep disorders， including 13 core targets. Go enrichment analysis suggested that the action mechanism of baihe zhimu decoction was related to the regulation of neurotransmitter level， cell response to organic cyclic compounds and neurotransmitter receptor activity. KEGG pathway analysis suggested that HIF-1 signaling pathway， cGMP-PKG signaling pathway and Relaxin signaling pathway might be potential pathways. Molecular docking showed that the core target protein had good affinity with the core active component of baihe zhimu decoction. Conclusion： Baihe zhimu decoction can treat sleep disorders through a variety of active molecules， multiple targets and multiple pathways， which provides a pharmacological theoretical basis for the follow-up study.

Key words: Baihe zhimu decoction, Sleep disorder, Network pharmacology, Action mechanism, Signal pathway

中图分类号:

R749.79

倪骥杰, 常秋伊. 基于网络药理学及分子对接探讨百合知母汤治疗睡眠障碍的活性成分及作用机制[J]. 中国医药导刊, 2021, 23(8): 574-580.

and Molecular Docking. Study of Action Mechanism and Active Ingredients of Baihe Zhimu Decoction in the Treatment of Sleep Disorders Based on Network Pharmacology and Molecular Docking[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2021, 23(8): 574-580.

参考文献

[1]刘鹏飞，康天威，白晶梅，等.甘肃省成年人失眠状况调查与因素分析及对策[J]. 中国初级卫生保健，2019，33(7)：60-61.
     [2]栗克清，石贺敏，贾海玲，等.河北省18岁以上人群睡眠障碍流行病学调查[C]. 中国睡眠研究会第十一届全国学术年会论文汇编[C]. 中国睡眠研究会，2019：1.
     [3]韩芳，唐向东，张斌.中国失眠症诊断和治疗指南[J]. 中华医学杂志，2017，97(24)：1844-1856.
     [4]李廖英子，刘敏.《伤寒杂病论》治疗失眠药对探析[J]. 环球中医药，2021，14(6)：1055-1058.
     [5]车贝贝，高晶蓉，陈德，等.上海市中学生抑郁症状流行现状及行为因素对其影响分析[J]. 中国健康教育，2021，37(1)：27-32.
     [6]李海龙，高淑怡，高英，等.百合知母总皂苷镇静催眠的药效学研究[J]. 北方药学，2012，9(10)：34-35，28.
     [7]袁莉，李贵明，姚祖培，等.百合知母汤加减治疗尿毒症患者顽固性失眠2例[J]. 中国中西医结合肾病杂志，2019，20(8)：737-738.
     [8]靳玉梅.百合知母汤加减联合甘麦大枣汤与盐酸氟西汀治疗抑郁症的临床观察[J]. 中国民间疗法，2018，26(11)：73-74.
     [9]杨铭.中药网络药理学分析系统v1.0[CP/CD]，著作权登记号：2019SR1127090.
     [10]Trott O， Olson AJ.AutoDock Vina： improving the speed and accuracy of docking with a new scoring function， efficient optimization and multithreading[J]. J Comput Chem，2010，31：455-461.
     [11]方前波，秦昆明，潘扬，等.百合知母汤的化学成分研究(Ⅰ)[J]. 中草药，2010，41(4)：517-520.
     [12]Pinzi L， Rastelli G. Molecular docking： shifting paradigms in drug discovery[J]. Int J Mol Sci，2019，20(18)：4331.
     [13]Golub MS， Hogrefe CE. Sleep patterns in male juvenile monkeys are influenced by gestational iron deprivation and MAOA genotype[J]. Br J Nutr， 2014， 112(9)：1478-1483.
     [14]Matthew DR， Liangyu C， Taishi P， et al. Tumor necrosis factor alpha in sleep regulation[J]. Sleep Med Rev， 2018， 40：69-78.
     [15]Ribera J， Marsal J， Casanovas A， et al. Nitric oxide synthase in rat neuromuscular junctions and in nerve terminals of torpedo electric organ： its role as regulator of acetylcholine release[J]. J Neuro Sci Res， 2015， 51(1)：90-102.
     [16]Medow MS， Del Pozzi A， Messer Z， et al. Cutaneous nitric oxide (NO) modulates noradrenergic neurotransmission pre-and post-synaptically； excess nitric oxide (NO) blunts presynaptic adrenergic transduction in orthostatic intolerance (OI)[J]. Autonomic Neuroscience Basic & Clinical， 2015， 192：99-99.
     [17]Kristofikova Z， Sirova J， Klaschka J， et al. Acute and chronic sleep deprivation-related changes in N-methyl-D-aspartate receptor—nitric oxide signalling in the rat cerebral cortex with reference to aging and brain lateralization[J]. Int J Mol Sci， 2019， 20(13)：3273.
     [18]严云飞，李生花，靳国恩，等.高原低氧状态下大鼠肺组织HIF-1α，CaMKⅡδ及血清HIF-1α的表达及相互关系[J]. 青海医学院学报，2012,33(1)：23-26.
     [19]刘佩蓉，张瑜，桂敏，等.电针对术后认知功能障碍大鼠认知功能及海马TNF-α和IL-1β表达的影响[J]. 上海针灸杂志，2017，36(9)：1116-1120.
     [20]Erwin S， Margot E. The benzodiazepine binding sites of GABAA receptors [J]. Trends Pharmacol Sci， 2018， 39(7)：659-671.
     [21]Ma S， Smith CM， Blasiak A， et al. Distribution， physiology and pharmacology of relaxin-3/RXFP3 systems in brain[J]. British Journal of Pharmacology， 2016， 174(10)：1034-1048.
     [22]李子雯，贾丹，党院霞，等.百合知母汤总皂苷调节5-HT功能治疗抑郁症的作用机制[J]. 中国实验方剂学杂志，2018，24(19)：131-138.
     [23]刘奇，袁丽，李德顺，等.百合知母汤对抑郁症大鼠行为及单胺递质的影响[J]. 中华中医药学刊，2016，34(7)：1729-1732.

快速检索引用检索图表检索高级检索