{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:05:16Z","timestamp":1792631116591,"version":"4.5.0"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.jep.2020.113549","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T20:08:55Z","timestamp":1604347735000},"page":"113549","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":78,"special_numbering":"C","title":["Integrating hippocampal metabolomics and network pharmacology deciphers the antidepressant mechanisms of Xiaoyaosan"],"prefix":"10.1016","volume":"268","author":[{"given":"Xiaojie","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxiao","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanle","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanhua","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jep.2020.113549_bib1","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/j.1471-4159.2006.03913.x","article-title":"The glutamate\/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer","volume":"98","author":"Bak","year":"2006","journal-title":"J. Neurochem."},{"key":"10.1016\/j.jep.2020.113549_bib2","doi-asserted-by":"crossref","DOI":"10.1038\/s41398-019-0521-7","article-title":"Biomarkers for response in major depression: comparing paroxetine and venlafaxine from two randomised placebo-controlled clinical studies","author":"Carboni","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"10.1016\/j.jep.2020.113549_bib3","article-title":"Studies on the potential link between antidepressant effect of Xiaoyao San and its pharmacological activity of hepatoprotection based on multi-platform metabolomics","author":"Chen","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2020.113549_bib4","doi-asserted-by":"crossref","DOI":"10.1080\/13880209.2019.1598445","article-title":"Chronic unpredictable mild stress induced depression-like behaviours and glutamate-glutamine cycling dysfunctions in both blood and brain of mice","author":"Chen","year":"2019","journal-title":"Pharm. Biol."},{"key":"10.1016\/j.jep.2020.113549_bib5","doi-asserted-by":"crossref","DOI":"10.1097\/01.WCB.0000081369.51727.6F","article-title":"Energy substrates for neurons during neural activity: a critical review of the astrocyte-neuron lactate shuttle hypothesis","author":"Chih","year":"2003","journal-title":"J. Cerebr. Blood Flow Metabol."},{"key":"10.1016\/j.jep.2020.113549_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.ajp.2017.01.025","article-title":"The neurobiology of depression: an integrated view","author":"Dean","year":"2017","journal-title":"Asian J. Psychiatr."},{"key":"10.1016\/j.jep.2020.113549_bib7","doi-asserted-by":"crossref","DOI":"10.1186\/s12906-017-1830-0","article-title":"Involvement of the glutamate\/glutamine cycle and glutamate transporter GLT-1 in antidepressant-like effects of Xiao Yao san on chronically stressed mice","author":"Ding","year":"2017","journal-title":"BMC Compl. Alternative Med."},{"key":"10.1016\/j.jep.2020.113549_bib8","article-title":"Quercetin alleviates LPS-induced depression-like behavior in rats via regulating BDNF-related imbalance of copine 6 and TREM1\/2 in the hippocampus and PFC","author":"Fang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jep.2020.113549_bib9","doi-asserted-by":"crossref","first-page":"5700","DOI":"10.12659\/MSM.915170","article-title":"Network pharmacology-based pharmacological mechanism of the Chinese medicine rhizoma drynariae against osteoporosis","volume":"25","author":"Gan","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"10.1016\/j.jep.2020.113549_bib10","first-page":"481","article-title":"Energy metabolism mechanism of Xiaoyaosan in treatment of depression based on integrative pharmacology-based research platform of traditional Chinese medicine","volume":"33","author":"Gao","year":"2019","journal-title":"Chin. J. Pharmacol. Toxicol."},{"key":"10.1016\/j.jep.2020.113549_bib11","doi-asserted-by":"crossref","DOI":"10.1007\/s11011-019-0389-5","article-title":"Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory cytokines and up-regulation of AKT\/\u03b2-catenin cascade","author":"Gao","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"10.1016\/j.jep.2020.113549_bib12","article-title":"Coniferyl ferulate exerts antidepressant effect via inhibiting the activation of NMDAR-CaMKII-MAPKs and mitochondrial apoptotic pathways","author":"Gong","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2020.113549_bib13","article-title":"Clinical application of metabolomics in pancreatic diseases: a mini-review","author":"Gu","year":"2020","journal-title":"Lab. Med."},{"key":"10.1016\/j.jep.2020.113549_bib14","doi-asserted-by":"crossref","DOI":"10.1002\/ar.24386","article-title":"Xiaoyaosan regulates depression-related behaviors with physical symptoms by modulating Orexin A\/OxR1 in the hypothalamus","author":"Hou","year":"2020","journal-title":"Anat. Rec."},{"key":"10.1016\/j.jep.2020.113549_bib15","doi-asserted-by":"crossref","DOI":"10.1080\/01616412.2019.1576361","article-title":"Antidepressant-like effects of paeoniflorin on post-stroke depression in a rat model","author":"Hu","year":"2019","journal-title":"Neurol. Res."},{"key":"10.1016\/j.jep.2020.113549_bib16","doi-asserted-by":"crossref","DOI":"10.1038\/s41398-017-0078-2","article-title":"Metabolite identification in fecal microbiota transplantation mouse livers and combined proteomics with chronic unpredictive mild stress mouse livers","author":"Li","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"10.1016\/j.jep.2020.113549_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbr.2016.08.001","article-title":"GC-MS-based metabolomic study on the antidepressant-like effects of diterpene ginkgolides in mouse hippocampus","author":"Liang","year":"2016","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.jep.2020.113549_bib18","doi-asserted-by":"crossref","DOI":"10.1007\/s00213-019-05257-5","article-title":"Paeoniflorin attenuates impairment of spatial learning and hippocampal long-term potentiation in mice subjected to chronic unpredictable mild stress","author":"Liu","year":"2019","journal-title":"Psychopharmacology (Berl)"},{"key":"10.1016\/j.jep.2020.113549_bib19","article-title":"Brain metabonomics study of the antidepressant-like effect of Xiaoyaosan on the CUMS-depression rats by 1H NMR analysis","author":"Liu","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2020.113549_bib20","article-title":"Plasma metabolomics of depressed patients and treatment with Xiaoyaosan based on mass spectrometry technique","author":"Liu","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2020.113549_bib21","doi-asserted-by":"crossref","DOI":"10.1186\/s12906-019-2613-6","article-title":"Xiaoyaosan exerts antidepressant-like effects by regulating the functions of astrocytes and EAATs in the prefrontal cortex of mice","author":"Liu","year":"2019","journal-title":"BMC Compl. Alternative Med."},{"key":"10.1016\/j.jep.2020.113549_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.mcp.2019.101470","article-title":"MiR-124 ameliorates depressive-like behavior by targeting STAT3 to regulate microglial activation","author":"Lou","year":"2019","journal-title":"Mol. Cell. Probes"},{"key":"10.1016\/j.jep.2020.113549_bib23","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s11655-019-3064-0","article-title":"Network pharmacology in research of Chinese medicine formula: methodology, application and prospective","volume":"26","author":"Luo","year":"2020","journal-title":"Chin. J. Integr. Med."},{"key":"10.1016\/j.jep.2020.113549_bib24","doi-asserted-by":"crossref","DOI":"10.3389\/fpsyt.2019.00910","article-title":"Xiaoyaosan ameliorates chronic immobilization stress-induced depression-like behaviors and anorexia in rats: the role of the Nesfatin-1-Oxytocin-Proopiomelanocortin neural pathway in the hypothalamus","author":"Ma","year":"2019","journal-title":"Front. Psychiatr."},{"key":"10.1016\/j.jep.2020.113549_bib25","doi-asserted-by":"crossref","DOI":"10.1186\/s12888-018-1596-z","article-title":"Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population","author":"Segoviano-Mendoza","year":"2018","journal-title":"BMC Psychiatry"},{"key":"10.1016\/j.jep.2020.113549_bib26","article-title":"The Mitogen-Activated Protein Kinase (MAPK) signaling pathway as a discovery target in stroke","author":"Sun","year":"2016","journal-title":"J. Mol. Neurosci."},{"key":"10.1016\/j.jep.2020.113549_bib27","doi-asserted-by":"crossref","DOI":"10.1007\/s12017-019-08538-6","article-title":"Antidepressant and neuroprotective effects of naringenin via sonic Hedgehog-GLI1 cell signaling pathway in a rat model of chronic unpredictable mild stress","author":"Tayyab","year":"2019","journal-title":"NeuroMolecular Med."},{"key":"10.1016\/j.jep.2020.113549_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.109833","article-title":"GC-MS based metabolomic profiling of lung tissue couple with network pharmacology revealed the possible protection mechanism of Pudilan Xiaoyan Oral Liquid in LPS-induced lung injury of mice","author":"Tian","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jep.2020.113549_bib29","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.brainresbull.2017.12.001","article-title":"Effects of xiao yao san on interferon-\u03b1-induced depression in mice","volume":"139","author":"Wang","year":"2018","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.jep.2020.113549_bib30","doi-asserted-by":"crossref","DOI":"10.3389\/fpsyt.2020.00141","article-title":"Differential regulation of DNA methylation at the CRMP2 promoter region between the hippocampus and prefrontal cortex in a CUMS depression model","author":"Xiang","year":"2020","journal-title":"Front. Psychiatr."},{"key":"10.1016\/j.jep.2020.113549_bib31","doi-asserted-by":"crossref","DOI":"10.21037\/atm.2019.09.39","article-title":"Antidepressant-like effects of the Guanxin Danshen formula via mediation of the CaMK II-CREB-BDNF signalling pathway in chronic unpredictable mild stress-induced depressive rats","author":"Xie","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"10.1016\/j.jep.2020.113549_bib32","doi-asserted-by":"crossref","DOI":"10.1002\/bmc.4878","article-title":"Uncovering the anticancer mechanism of petroleum extracts of Farfarae Flos against Lewis lung cancer by metabolomics and network pharmacology analysis","author":"Yu","year":"2020","journal-title":"Biomed. Chromatogr."},{"key":"10.1016\/j.jep.2020.113549_bib33","article-title":"An integrated pharmacology-based analysis for antidepressant mechanism of Chinese herbal formula Xiao-Yao-San","author":"Yuan","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jep.2020.113549_bib34","doi-asserted-by":"crossref","DOI":"10.1159\/000501995","article-title":"Xiaoyaosan produces antidepressant effects in rats via the JNK signaling pathway","author":"Zhao","year":"2020","journal-title":"Complement. Med. Res."},{"key":"10.1016\/j.jep.2020.113549_bib35","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/4202563","article-title":"Network pharmacology analysis of traditional Chinese medicine formula Xiao Ke Yin Shui treating type 2 diabetes mellitus","author":"Zhou","year":"2019","journal-title":"Evid. Based Complement. Alternat. Med."}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874120334371?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874120334371?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:56:46Z","timestamp":1759942606000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874120334371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":35,"alternative-id":["S0378874120334371"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2020.113549","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Integrating hippocampal metabolomics and network pharmacology deciphers the antidepressant mechanisms of Xiaoyaosan","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2020.113549","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"113549"}}