Article(id=1304415545693066114, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304415531491152712, articleNumber=null, orderNo=null, doi=10.7501/j.issn.0253-2670.2026.09.019, pmid=null, cstr=null, oa=null, hot=0, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1758556800000, receivedDateStr=2025-09-23, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1788926500961, onlineDateStr=2026-09-09, pubDate=null, pubDateStr=null, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1788926500961, onlineIssueDateStr=2026-09-09, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1788926500961, creator=13701087609, updateTime=1788926500961, updator=13701087609, issue=Issue{id=1304415531491152712, tenantId=1146029695717560320, journalId=1302319053441957962, year='2026', volume='57', issue='9', pageStart='3261', pageEnd='3684', issueExtLink='null', onlineDate='null', pubDate='1778515200000', pubDateStr='2026-05-12', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1788926497576, creator='13701087609', updateTime=1788926796984, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1304416787358049066, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304415531491152712, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1304416787358049067, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304415531491152712, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=3495, endPage=3507, ext={EN=ArticleExt(id=1304415546036999044, articleId=1304415545693066114, tenantId=1146029695717560320, journalId=1302319053441957962, language=EN, title=Analysis on sedative hypnotic mechanism of Ziziphi Spinosae Semen-Ginseng Radix et Rhizoma herb pair based on data mining and network pharmacology, columnId=null, journalTitle=Chinese Traditional and Herbal Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=Objective Discovering the ancient and modern Chinese compound prescriptions containing Suanzaoren (Ziziphi Spinosae Semen)-(Renshen) Ginseng Radix et Rhizoma herb pair (ZSS-GRR) and further analyzing the diseases commonly treated by the pairs and their therapeutic mechanisms. Methods Data mining method was applied to collect the compound formulas containing ZSS-GRR and count the commonly treated diseases and pharmacological effects, network pharmacology was applied to predict the mechanism of ZSS-GRR herb pair, and molecular docking technique was used to verify the binding ability of candidate compounds to potential targets, and finally enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to validate the discovered mechanisms of ZSS-GRR for insomnia and nervous system function. Results A total of 596 compound formulations containing the ZSS-GRR were searched. Statistical analysis of the pharmacological effects of these formulations revealed that the ZSS-GRR primarily exerts sedative and hypnotic effects and is commonly used to treat conditions such as insomnia. Network pharmacology analysis indicates that the ZSS-GRR may exert its sedative and hypnotic effects by regulating neuroactive ligand-receptor interactions, gamma-aminobutyric acid (GABA) ergic synapses, and inflammation-related pathways. Molecular docking results suggest that multiple core active components exhibit strong binding affinity with key targets. Experimental results demonstrate that the ZSS-GRR combination can alleviate glutamate-induced damage in SH-SY5Y cells, increase levels of relevant neurotransmitters in rats with an insomnia model, reduce levels of inflammatory factors, and promote the expression of gamma-aminobutyric acid type A receptor subunit alpha 1 (GABRA1) and gamma-aminobutyric acid type A receptor subunit gamma 2 (GABRG2) in the hippocampus and hypothalamus. Conclusion Through the exploration of the commonly treated diseases and the sedative-hypnotic mechanism of ZSS-GRR, the main direction and mechanism of action of ZSS-GRR have been revealed, which provides certain valuable references for the subsequent in-depth research and clinical application of the pair., authors=LU Chunyang, XU Zhijia, LI Xue, MENG Lingkun, ZHANG Hongyin, LI Guangzhe, YAN Mingming, authorsList=LU Chunyang, XU Zhijia, LI Xue, MENG Lingkun, ZHANG Hongyin, LI Guangzhe, YAN Mingming, authorCompany=null, correspAuthors=null, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1304415545944724355, articleId=1304415545693066114, tenantId=1146029695717560320, journalId=1302319053441957962, language=CN, title=基于数据挖掘和网络药理学探析酸枣仁-人参药对的镇静催眠作用机制, columnId=1304140194819629763, journalTitle=中草药, columnName=数据挖掘与循证医学, runingTitle=null, highlight=null, articleAbstract=目的 挖掘中国古今含酸枣仁-人参药对的复方,并进一步分析药对常治疾病及机制。方法 应用数据挖掘收集含有酸枣仁-人参药对的复方并统计药对常治疾病及药理作用,运用网络药理学预测酸枣仁-人参药对常治疾病机制,并且使用分子对接技术验证候选化合物与潜在靶标的结合能力,最后运用酶联免疫吸附法和免疫组织化学技术验证所发现的酸枣仁-人参药对失眠与神经系统功能的调节机制。结果 检索得到含酸枣仁-人参药对复方596首,经复方药理作用挖掘统计发现酸枣仁-人参药对主要发挥镇静催眠作用,常用于治疗失眠症等疾病。网络药理学分析结果显示,酸枣仁-人参药对可能通过调控神经活性配体-受体相互作用、γ-氨基丁酸(gamma-aminobutyric acid,GABA)能突触及炎症相关通路发挥镇静催眠作用。分子对接结果表明,多种核心活性成分与关键靶点具有较好的结合活性。体内外实验结果显示,酸枣仁-人参药对可改善谷氨酸诱导的SH-SY5Y细胞损伤,提高失眠模型大鼠相关神经递质水平,降低炎症因子水平,并促进海马及下丘脑中γ-氨基丁酸A型受体亚基α1(gamma-aminobutyric acid type A receptor subunit alpha1,GABRA1)和γ-氨基丁酸A型受体亚基γ2(gamma-aminobutyric acid type A receptor subunit gamma 2,GABRG2)的表达。结论 通过对酸枣仁-人参药对常治疾病的挖掘和发挥镇静催眠机制的探索,揭示了酸枣仁-人参药对的主要用药方向及作用机制,为该药对后续的深入研究及临床应用提供了一定的参考。, 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detailUrlEn=https://castjournals.cast.org.cn/joweb/zcy/EN/10.7501/j.issn.0253-2670.2026.09.019, pdfUrlCn=https://castjournals.cast.org.cn/joweb/zcy/CN/PDF/10.7501/j.issn.0253-2670.2026.09.019, pdfUrlEn=https://castjournals.cast.org.cn/joweb/zcy/EN/PDF/10.7501/j.issn.0253-2670.2026.09.019, aliStartDate=null, aliEndDate=null, collectionFlag=false, citedCount=null, citedUrl=null, previewStatus=0, delFlag=0, hasFullText=0, orderTime=1788926500961, fullTextJson=null, articleText=null, reference=张诗嘉.基于数据挖掘分析刘朝霞教授治疗胃食管反流病的用药规律[D].哈尔滨:黑龙江中医药大学,2022. Zhang H, Liu W, Qi S M, et al. Improved effect of fresh ginseng paste(Radix ginseng-Ziziphus Jujube)on hyperuricemia based on network pharmacology and molecular docking[J]. Front Pharmacol, 2022, 13:955219. 姚玉静,张书敏,任艳艳,等.酸枣仁提取物、龙眼肉提取物、γ-氨基丁酸和酪蛋白水解物复配制剂改善睡眠功能[J].食品工业科技, 2023, 44(7):406-410. Li F T, Yang D, Song F Y, et al. In vitro effects of ginseng and the seed of Zizyphus jujuba var. spinosa on gut microbiota of rats with spleen deficiency[J]. Chem Biodivers, 2020, 17(9):e2000199. Liu M, Cai Y Y, Li F T, et al. Metabolomics and network pharmacological analysis to explore the mechanism of ginseng treatment for spleen-qi deficiency[J]. J Sep Sci,2022, 45(24):4427-4438. Bian Z H, Zhang W M, Tang J Y, et al. Mechanisms underlying the action of Ziziphi Spinosae Semen in the treatment of insomnia:A study involving network pharmacology and experimental validation[J]. Front Pharmacol, 2021, 12:752211. 徐敬娅,马欣雨,赵佳鹤,等.人参、附子药对配伍及其温阳功效研究概况[J].河北中医, 2022, 44(7):1224-1228. 王媛.基于“脑肠轴”探讨药对人参-酸枣仁对心脾两虚失眠大鼠的影响[D].沈阳:辽宁中医药大学, 2022. 吴艳,杜娟,张晓雷. UHPLC-TOF-MS结合网络药理学与分子对接探讨人参-酸枣仁药对治疗帕金森的作用机制[J].中国现代应用药学, 2025, 42(20):3559-3568. 张经北.基于数据挖掘分析古代名医治疗不寐医案中用药规律[D].长春:长春中医药大学, 2023. 任海琴,孔祥鹏,王颖莉.基于古今方剂数据挖掘的酸枣仁-远志药对配伍特点及外延分析[J].中草药,2022, 53(13):4065-4074. 中国药典[S].一部. 2025:431. 冉小峰,胡长鸿.全国中药成药处方集[M].北京:人民卫生出版社, 1962:34-73. Ru J L, Li P, Wang J N, et al. TCMSP:A database of systems pharmacology for drug discovery from herbal medicines[J]. J Cheminf, 2014, 6(1):13. Xue R C, Fang Z, Zhang M X, et al. TCMID:Traditional Chinese medicine integrative database for herb molecular mechanism analysis[J]. Nucleic Acids Res, 2012, 41(D1):D1089-D1095. Upton D H, Liu J, George S M, et al. High-throughput in vitro drug screening and in vivo studies identify fenretinide as a brain-penetrant DMG therapeutic[J]. Neuro Oncol,2025, 27(7):1813-1828. Zhang Y Q, Guo Q Y, Li Q Y, et al. Main active constituent identification in Guanxinjing Capsule, a traditional Chinese medicine, for the treatment of coronary heart disease complicated with depression[J]. Acta Pharmacol Sin, 2018, 39(6):975-987. Daina A, Michielin O, Zoete V. SwissTargetPrediction:Updated data and new features for efficient prediction of protein targets of small molecules[J]. Nucleic Acids Res,2019, 47(W1):W357-W364. Safran M, Dalah I, Alexander J, et al. GeneCards Version3:The human gene integrator[J]. Database J Biol Databases Curation, 2010, 2010:baq020. Queralt-Rosinach N, Piñero J, BravoÀ, et al. DisGeNETRDF:Harnessing the innovative power of the Semantic Web to explore the genetic basis of diseases[J].Bioinformatics, 2016, 32(14):2236-2238. Wishart D S, Feunang Y D, Guo A C, et al. DrugBank 5.0:A major update to the DrugBank database for 2018[J].Nucleic Acids Res, 2018, 46(D1):D1074-D1082. Zhou Y, Zhang Y T, Lian X C, et al. Therapeutic target database update 2022:Facilitating drug discovery with enriched comparative data of targeted agents[J]. Nucleic Acids Res, 2022, 50(D1):D1398-D1407. Whirl-Carrillo M, McDonagh E M, Hebert J M, et al.Pharmacogenomics knowledge for personalized medicine[J]. Clin Pharmacol Ther, 2012, 92(4):414-417. Soudy M, Anwar A M, Ali Ahmed E, et al. UniprotR:Retrieving and visualizing protein sequence and functional information from Universal Protein Resource(UniProt knowledgebase)[J]. J Proteom, 2020, 213:103613. Szklarczyk D, Gable A L, Lyon D, et al. STRING v11:Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Res, 2019,47(D1):D607-D613. Sherman B T, Hao M, Qiu J, et al. DAVID a web server for functional enrichment analysis and functional annotation of gene lists(2021 update)[J]. Nucleic Acids Res, 2022,50(W1):W216-W221. 翁小建,谈毅,高秀飞.基于网络药理学与生物信息学预测大枣抗焦虑、抗抑郁的潜在活性成分及作用机制[J].浙江中西医结合杂志, 2022, 32(4):359-363. Bae G Y, Ahn Y, Hong K B, et al. Sleep-enhancing effect of water extract from jujube(Zizyphus jujuba Mill.)seeds fermented by Lactobacillus brevis L32[J]. Foods, 2023,12(15):2864. Hua Y, Guo S, Xie H, et al. Ziziphus jujuba Mill. var.spinosa(Bunge)Hu ex H. F. Chou seed ameliorates insomnia in rats by regulating metabolomics and intestinal flora composition[J]. Front Pharmacol, 2021, 12:653767. Cui X F, Zhang S M, He L, et al. In vitro biotransformation of Ziziphi Spinosae Semen saponins by gut microbiota from healthy and insomniac groups[J]. Int J Mol Sci, 2025,26(9):4011. Kim S, Chen J, Cheng T J, et al. PubChem 2023 update[J]. Nucleic Acids Res, 2023, 51(D1):D1373-D1380. K S B, Charmi B, Chunxiao B, et al. RCSB Protein Data Bank(RCSB.org):Delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning[J]. Nucleic Acids Res, 2022, 51(D1):D488-D508. 肖凤琴,王欣,刘晖,等.基于熵权法和灰色关联度法优选人参-酸枣仁抗氧化活性最佳配比[J].食品与机械, 2023, 39(6):173-179. 肖凤琴.人参-酸枣仁药对药效物质基础及对ROT诱导的帕金森模型的神经保护作用研究[D].长春:长春中医药大学, 2023. 郭海波,王慧.对氯苯丙氨酸在动物失眠模型中的应用概述[J].中国比较医学杂志, 2019, 29(6):135-140. 丁环宇,洪勇良,齐凤军,等.“君臣佐使”于临床的创新应用[J].时珍国医国药, 2022, 33(5):1178-1179. Zhao N, Zhao Y J, An F R, et al. Network analysis of comorbid insomnia and depressive symptoms among psychiatric practitioners during the COVID-19 pandemic[J]. J Clin Sleep Med, 2023, 19(7):1271-1279. Selbæk-Tungevåg S, Selbæk G, Strand B H, et al.Insomnia and risk of dementia in a large population-based study with 11-year follow-up:The HUNT study[J]. J Sleep Res, 2023, 32(4):e13820. Yang Y N, Su W Q, Zang C C, et al. Traditional Chinese medicines(TCMs)with varied meridians(Gui-Jing)differentially alleviate the adverse impact of Coptis chinensis on gut microbiota[J]. J Ethnopharmacol, 2023,307:116256. 赵萱,陈云慧,郑明月,等.基于数据挖掘的含人参-附子药对方剂的组方规律分析[J].中草药, 2021,53(4):1083-1091. Xiao F Q, Shao S, Zhang H Y, et al. Neuroprotective effect of Ziziphi Spinosae Semen on rats with pchlorophenylalanine-induced insomnia via activation of GABAA receptor[J]. Front Pharmacol, 2022, 13:965308. de Oliveira Zanuso B, de Oliveira dos Santos A R, Miola V F B, et al. Panax ginseng and aging related disorders:A systematic review[J]. Exp Gerontol, 2022, 161:111731. Li R, Wang L, Wang X, et al. Simultaneous determination of four monoamine neurotransmitters and seven effective components of Zaoren Anshen prescription in rat tissue using UPLC-MS/MS[J]. Curr Pharm Anal, 2021, 17(1):67-80. Qiao T, Wang Y, Liang K, et al. Effects of the Radix Ginseng and Semen Ziziphi Spinosae drug pair on the GLU/GABA-GLN metabolic cycle and the intestinal microflora of insomniac rats based on the brain-gut axis[J]. Front Pharmacol, 2022, 13:1094507.)
Analysis on sedative hypnotic mechanism of Ziziphi Spinosae Semen-Ginseng Radix et Rhizoma herb pair based on data mining and network pharmacology
LU Chunyang, XU Zhijia, LI Xue, MENG Lingkun, ZHANG Hongyin, LI Guangzhe, YAN Mingming
Affiliations
doi: 10.7501/j.issn.0253-2670.2026.09.019
文章导航
摘要
收起
目的 挖掘中国古今含酸枣仁-人参药对的复方,并进一步分析药对常治疾病及机制。方法 应用数据挖掘收集含有酸枣仁-人参药对的复方并统计药对常治疾病及药理作用,运用网络药理学预测酸枣仁-人参药对常治疾病机制,并且使用分子对接技术验证候选化合物与潜在靶标的结合能力,最后运用酶联免疫吸附法和免疫组织化学技术验证所发现的酸枣仁-人参药对失眠与神经系统功能的调节机制。结果 检索得到含酸枣仁-人参药对复方596首,经复方药理作用挖掘统计发现酸枣仁-人参药对主要发挥镇静催眠作用,常用于治疗失眠症等疾病。网络药理学分析结果显示,酸枣仁-人参药对可能通过调控神经活性配体-受体相互作用、γ-氨基丁酸(gamma-aminobutyric acid,GABA)能突触及炎症相关通路发挥镇静催眠作用。分子对接结果表明,多种核心活性成分与关键靶点具有较好的结合活性。体内外实验结果显示,酸枣仁-人参药对可改善谷氨酸诱导的SH-SY5Y细胞损伤,提高失眠模型大鼠相关神经递质水平,降低炎症因子水平,并促进海马及下丘脑中γ-氨基丁酸A型受体亚基α1(gamma-aminobutyric acid type A receptor subunit alpha1,GABRA1)和γ-氨基丁酸A型受体亚基γ2(gamma-aminobutyric acid type A receptor subunit gamma 2,GABRG2)的表达。结论 通过对酸枣仁-人参药对常治疾病的挖掘和发挥镇静催眠机制的探索,揭示了酸枣仁-人参药对的主要用药方向及作用机制,为该药对后续的深入研究及临床应用提供了一定的参考。
关键词
人参
/
酸枣仁
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药对
/
数据挖掘
/
网络药理学
/
分子对接
/
失眠症
Abstract
收起
Objective Discovering the ancient and modern Chinese compound prescriptions containing Suanzaoren (Ziziphi Spinosae Semen)-(Renshen) Ginseng Radix et Rhizoma herb pair (ZSS-GRR) and further analyzing the diseases commonly treated by the pairs and their therapeutic mechanisms. Methods Data mining method was applied to collect the compound formulas containing ZSS-GRR and count the commonly treated diseases and pharmacological effects, network pharmacology was applied to predict the mechanism of ZSS-GRR herb pair, and molecular docking technique was used to verify the binding ability of candidate compounds to potential targets, and finally enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to validate the discovered mechanisms of ZSS-GRR for insomnia and nervous system function. Results A total of 596 compound formulations containing the ZSS-GRR were searched. Statistical analysis of the pharmacological effects of these formulations revealed that the ZSS-GRR primarily exerts sedative and hypnotic effects and is commonly used to treat conditions such as insomnia. Network pharmacology analysis indicates that the ZSS-GRR may exert its sedative and hypnotic effects by regulating neuroactive ligand-receptor interactions, gamma-aminobutyric acid (GABA) ergic synapses, and inflammation-related pathways. Molecular docking results suggest that multiple core active components exhibit strong binding affinity with key targets. Experimental results demonstrate that the ZSS-GRR combination can alleviate glutamate-induced damage in SH-SY5Y cells, increase levels of relevant neurotransmitters in rats with an insomnia model, reduce levels of inflammatory factors, and promote the expression of gamma-aminobutyric acid type A receptor subunit alpha 1 (GABRA1) and gamma-aminobutyric acid type A receptor subunit gamma 2 (GABRG2) in the hippocampus and hypothalamus. Conclusion Through the exploration of the commonly treated diseases and the sedative-hypnotic mechanism of ZSS-GRR, the main direction and mechanism of action of ZSS-GRR have been revealed, which provides certain valuable references for the subsequent in-depth research and clinical application of the pair.
Key words
Ginseng Radix et Rhizoma
/
Ziziphi Spinosae Semen
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herb pair
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data mining
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network pharmacology
/
molecular docking
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insomnia
LU Chunyang, XU Zhijia, LI Xue, MENG Lingkun, ZHANG Hongyin, LI Guangzhe, YAN Mingming.
Analysis on sedative hypnotic mechanism of Ziziphi Spinosae Semen-Ginseng Radix et Rhizoma herb pair based on data mining and network pharmacology[J].
Chinese Traditional and Herbal Drugs,
2026
, 57
(9)
: 3495
-3507
.
DOI: 10.7501/j.issn.0253-2670.2026.09.019
张诗嘉.基于数据挖掘分析刘朝霞教授治疗胃食管反流病的用药规律[D].哈尔滨:黑龙江中医药大学,2022. Zhang H, Liu W, Qi S M, et al. Improved effect of fresh ginseng paste(Radix ginseng-Ziziphus Jujube)on hyperuricemia based on network pharmacology and molecular docking[J]. Front Pharmacol, 2022, 13:955219. 姚玉静,张书敏,任艳艳,等.酸枣仁提取物、龙眼肉提取物、γ-氨基丁酸和酪蛋白水解物复配制剂改善睡眠功能[J].食品工业科技, 2023, 44(7):406-410. Li F T, Yang D, Song F Y, et al. In vitro effects of ginseng and the seed of Zizyphus jujuba var. spinosa on gut microbiota of rats with spleen deficiency[J]. Chem Biodivers, 2020, 17(9):e2000199. Liu M, Cai Y Y, Li F T, et al. Metabolomics and network pharmacological analysis to explore the mechanism of ginseng treatment for spleen-qi deficiency[J]. J Sep Sci,2022, 45(24):4427-4438. Bian Z H, Zhang W M, Tang J Y, et al. Mechanisms underlying the action of Ziziphi Spinosae Semen in the treatment of insomnia:A study involving network pharmacology and experimental validation[J]. Front Pharmacol, 2021, 12:752211. 徐敬娅,马欣雨,赵佳鹤,等.人参、附子药对配伍及其温阳功效研究概况[J].河北中医, 2022, 44(7):1224-1228. 王媛.基于“脑肠轴”探讨药对人参-酸枣仁对心脾两虚失眠大鼠的影响[D].沈阳:辽宁中医药大学, 2022. 吴艳,杜娟,张晓雷. UHPLC-TOF-MS结合网络药理学与分子对接探讨人参-酸枣仁药对治疗帕金森的作用机制[J].中国现代应用药学, 2025, 42(20):3559-3568. 张经北.基于数据挖掘分析古代名医治疗不寐医案中用药规律[D].长春:长春中医药大学, 2023. 任海琴,孔祥鹏,王颖莉.基于古今方剂数据挖掘的酸枣仁-远志药对配伍特点及外延分析[J].中草药,2022, 53(13):4065-4074. 中国药典[S].一部. 2025:431. 冉小峰,胡长鸿.全国中药成药处方集[M].北京:人民卫生出版社, 1962:34-73. Ru J L, Li P, Wang J N, et al. TCMSP:A database of systems pharmacology for drug discovery from herbal medicines[J]. J Cheminf, 2014, 6(1):13. Xue R C, Fang Z, Zhang M X, et al. TCMID:Traditional Chinese medicine integrative database for herb molecular mechanism analysis[J]. Nucleic Acids Res, 2012, 41(D1):D1089-D1095. Upton D H, Liu J, George S M, et al. High-throughput in vitro drug screening and in vivo studies identify fenretinide as a brain-penetrant DMG therapeutic[J]. Neuro Oncol,2025, 27(7):1813-1828. Zhang Y Q, Guo Q Y, Li Q Y, et al. Main active constituent identification in Guanxinjing Capsule, a traditional Chinese medicine, for the treatment of coronary heart disease complicated with depression[J]. Acta Pharmacol Sin, 2018, 39(6):975-987. Daina A, Michielin O, Zoete V. SwissTargetPrediction:Updated data and new features for efficient prediction of protein targets of small molecules[J]. Nucleic Acids Res,2019, 47(W1):W357-W364. Safran M, Dalah I, Alexander J, et al. GeneCards Version3:The human gene integrator[J]. Database J Biol Databases Curation, 2010, 2010:baq020. Queralt-Rosinach N, Piñero J, BravoÀ, et al. DisGeNETRDF:Harnessing the innovative power of the Semantic Web to explore the genetic basis of diseases[J].Bioinformatics, 2016, 32(14):2236-2238. Wishart D S, Feunang Y D, Guo A C, et al. DrugBank 5.0:A major update to the DrugBank database for 2018[J].Nucleic Acids Res, 2018, 46(D1):D1074-D1082. Zhou Y, Zhang Y T, Lian X C, et al. Therapeutic target database update 2022:Facilitating drug discovery with enriched comparative data of targeted agents[J]. Nucleic Acids Res, 2022, 50(D1):D1398-D1407. Whirl-Carrillo M, McDonagh E M, Hebert J M, et al.Pharmacogenomics knowledge for personalized medicine[J]. Clin Pharmacol Ther, 2012, 92(4):414-417. Soudy M, Anwar A M, Ali Ahmed E, et al. UniprotR:Retrieving and visualizing protein sequence and functional information from Universal Protein Resource(UniProt knowledgebase)[J]. J Proteom, 2020, 213:103613. Szklarczyk D, Gable A L, Lyon D, et al. STRING v11:Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Res, 2019,47(D1):D607-D613. Sherman B T, Hao M, Qiu J, et al. DAVID a web server for functional enrichment analysis and functional annotation of gene lists(2021 update)[J]. Nucleic Acids Res, 2022,50(W1):W216-W221. 翁小建,谈毅,高秀飞.基于网络药理学与生物信息学预测大枣抗焦虑、抗抑郁的潜在活性成分及作用机制[J].浙江中西医结合杂志, 2022, 32(4):359-363. Bae G Y, Ahn Y, Hong K B, et al. Sleep-enhancing effect of water extract from jujube(Zizyphus jujuba Mill.)seeds fermented by Lactobacillus brevis L32[J]. Foods, 2023,12(15):2864. Hua Y, Guo S, Xie H, et al. Ziziphus jujuba Mill. var.spinosa(Bunge)Hu ex H. F. Chou seed ameliorates insomnia in rats by regulating metabolomics and intestinal flora composition[J]. Front Pharmacol, 2021, 12:653767. Cui X F, Zhang S M, He L, et al. In vitro biotransformation of Ziziphi Spinosae Semen saponins by gut microbiota from healthy and insomniac groups[J]. Int J Mol Sci, 2025,26(9):4011. Kim S, Chen J, Cheng T J, et al. PubChem 2023 update[J]. Nucleic Acids Res, 2023, 51(D1):D1373-D1380. K S B, Charmi B, Chunxiao B, et al. RCSB Protein Data Bank(RCSB.org):Delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning[J]. Nucleic Acids Res, 2022, 51(D1):D488-D508. 肖凤琴,王欣,刘晖,等.基于熵权法和灰色关联度法优选人参-酸枣仁抗氧化活性最佳配比[J].食品与机械, 2023, 39(6):173-179. 肖凤琴.人参-酸枣仁药对药效物质基础及对ROT诱导的帕金森模型的神经保护作用研究[D].长春:长春中医药大学, 2023. 郭海波,王慧.对氯苯丙氨酸在动物失眠模型中的应用概述[J].中国比较医学杂志, 2019, 29(6):135-140. 丁环宇,洪勇良,齐凤军,等.“君臣佐使”于临床的创新应用[J].时珍国医国药, 2022, 33(5):1178-1179. Zhao N, Zhao Y J, An F R, et al. Network analysis of comorbid insomnia and depressive symptoms among psychiatric practitioners during the COVID-19 pandemic[J]. J Clin Sleep Med, 2023, 19(7):1271-1279. Selbæk-Tungevåg S, Selbæk G, Strand B H, et al.Insomnia and risk of dementia in a large population-based study with 11-year follow-up:The HUNT study[J]. J Sleep Res, 2023, 32(4):e13820. Yang Y N, Su W Q, Zang C C, et al. Traditional Chinese medicines(TCMs)with varied meridians(Gui-Jing)differentially alleviate the adverse impact of Coptis chinensis on gut microbiota[J]. J Ethnopharmacol, 2023,307:116256. 赵萱,陈云慧,郑明月,等.基于数据挖掘的含人参-附子药对方剂的组方规律分析[J].中草药, 2021,53(4):1083-1091. Xiao F Q, Shao S, Zhang H Y, et al. Neuroprotective effect of Ziziphi Spinosae Semen on rats with pchlorophenylalanine-induced insomnia via activation of GABAA receptor[J]. Front Pharmacol, 2022, 13:965308. de Oliveira Zanuso B, de Oliveira dos Santos A R, Miola V F B, et al. Panax ginseng and aging related disorders:A systematic review[J]. Exp Gerontol, 2022, 161:111731. Li R, Wang L, Wang X, et al. Simultaneous determination of four monoamine neurotransmitters and seven effective components of Zaoren Anshen prescription in rat tissue using UPLC-MS/MS[J]. Curr Pharm Anal, 2021, 17(1):67-80. Qiao T, Wang Y, Liang K, et al. Effects of the Radix Ginseng and Semen Ziziphi Spinosae drug pair on the GLU/GABA-GLN metabolic cycle and the intestinal microflora of insomniac rats based on the brain-gut axis[J]. Front Pharmacol, 2022, 13:1094507.