{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T07:20:09Z","timestamp":1787556009587,"version":"build-2736575974"},"reference-count":32,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003785","name":"Guangdong Provincial Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]},{"DOI":"10.13039\/501100012576","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012576","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.phymed.2026.158679","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:27:48Z","timestamp":1785799668000},"page":"158679","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Chaihu-Guizhi Decoction and Saikosaponin D alleviate anxiety-like behavior by engaging HTR2C-related neurotrophic and excitatory synaptic homeostasis"],"prefix":"10.1016","volume":"160","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2885-0157","authenticated-orcid":false,"given":"Gui-Yu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2481-516X","authenticated-orcid":false,"given":"Jun-Ming","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Qin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Juan","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Yong-Ming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Yu","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Zhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hong","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Peng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2026.158679_bib0001","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S2215-0366(21)00395-3","article-title":"Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"9","year":"2022","journal-title":"Lancet Psychiat."},{"key":"10.1016\/j.phymed.2026.158679_bib0002","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.biopsych.2010.12.006","article-title":"Chronic low-grade inflammation in elderly persons is associated with altered tryptophan and tyrosine metabolism: role in neuropsychiatric symptoms","volume":"70","author":"Capuron","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.phymed.2026.158679_bib0003","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00221-025-07011-0","article-title":"Saikosaponins alleviate depression-like behaviors of chronic unpredictable mild stress exposed mice through ERK signaling pathway","volume":"243","author":"Chen","year":"2025","journal-title":"Exp. Brain Res."},{"key":"10.1016\/j.phymed.2026.158679_bib0004","article-title":"Early life stress induces different behaviors in adolescence and adulthood may related with abnormal medial prefrontal cortex excitation\/inhibition balance","volume":"15","author":"Chen","year":"2021","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.phymed.2026.158679_bib0006","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.111324","article-title":"Saikosaponin-d alleviates depression by promoting NLRP3 ubiquitination and inhibiting inflammasome activation","volume":"127","author":"Gao","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.phymed.2026.158679_bib0007","doi-asserted-by":"crossref","DOI":"10.1016\/j.jpba.2020.113293","article-title":"Exploration of chemical composition and absorption characteristics of Chaigui granules based on UHPLC-Q-orbitrap-MS\/MS","volume":"187","author":"Gao","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"10.1016\/j.phymed.2026.158679_bib0008","first-page":"399","article-title":"Chaihu Guizhi decoction produces antidepressant-like effects via sirt1-p53 signaling pathway","volume":"41","author":"Ge","year":"2021","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"10.1016\/j.phymed.2026.158679_bib0009","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1003664","article-title":"Selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for anxiety, obsessive-compulsive, and stress disorders: A 3-level network meta-analysis","volume":"18","author":"Gosmann","year":"2021","journal-title":"PLoS Med."},{"key":"10.1016\/j.phymed.2026.158679_bib0010","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.neubiorev.2008.11.005","article-title":"Stress-induced prefrontal reorganization and executive dysfunction in rodents","volume":"33","author":"Holmes","year":"2009","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.phymed.2026.158679_bib0011","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neuron.2016.02.033","article-title":"Membrane lipids in presynaptic function and disease","volume":"90","author":"Lauwers","year":"2016","journal-title":"Neuron"},{"key":"10.1016\/j.phymed.2026.158679_bib0012","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.biopsych.2022.04.019","article-title":"Astrocytes mediate cholinergic regulation of adult hippocampal neurogenesis and memory through M1 muscarinic receptor","volume":"92","author":"Li","year":"2022","journal-title":"Biol. Psychiatry"},{"issue":"8","key":"10.1016\/j.phymed.2026.158679_bib0005","first-page":"2677","article-title":"Research progress on the clinical applications and pharmacological effects of Chaihu-Guizhi Decoction in neuropsychiatric disorders","volume":"46","author":"Li","year":"2024","journal-title":"Chinese Traditional Patent Medicine"},{"key":"10.1016\/j.phymed.2026.158679_bib0013","doi-asserted-by":"crossref","first-page":"0818","DOI":"10.34133\/research.0818","article-title":"Astrocytic BDNF modulates sensitivity to stress-induced anxiety-like behaviors","volume":"8","author":"Li","year":"2025","journal-title":"Research"},{"key":"10.1016\/j.phymed.2026.158679_bib0014","doi-asserted-by":"crossref","DOI":"10.3389\/fnsyn.2023.1124112","article-title":"Latest updates on the serotonergic system in depression and anxiety","volume":"15","author":"Lin","year":"2023","journal-title":"Front. Synaptic. Neurosci."},{"key":"10.1016\/j.phymed.2026.158679_bib0015","doi-asserted-by":"crossref","DOI":"10.1186\/s13020-022-00621-8","article-title":"Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress","volume":"17","author":"Liu","year":"2022","journal-title":"Chin. Med."},{"key":"10.1016\/j.phymed.2026.158679_bib0016","article-title":"Frontiers and hotspots in anxiety disorders: a bibliometric analysis from 2004 to 2024","volume":"10","author":"Liu","year":"2024","journal-title":"Heliyon"},{"key":"10.1016\/j.phymed.2026.158679_bib0017","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/npp.2015.171","article-title":"Stress effects on neuronal structure: hippocampus, amygdala, and prefrontal cortex","volume":"41","author":"McEwen","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.phymed.2026.158679_bib0018","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/S0140-6736(21)00359-7","article-title":"Anxiety disorders","volume":"397","author":"Penninx","year":"2021","journal-title":"Lancet"},{"key":"10.1016\/j.phymed.2026.158679_bib0019","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nrn3138","article-title":"The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission","volume":"13","author":"Popoli","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.phymed.2026.158679_bib0020","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41398-019-0431-8","article-title":"Increased 5-HT2C receptor editing predisposes to PTSD-like behaviors and alters BDNF and cytokines signaling","volume":"9","author":"Regue","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"10.1016\/j.phymed.2026.158679_bib0021","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s41583-021-00540-x","article-title":"The stressed synapse 2.0: pathophysiological mechanisms in stress-related neuropsychiatric disorders","volume":"23","author":"Sanacora","year":"2022","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.phymed.2026.158679_bib0022","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.neuropharm.2016.08.003","article-title":"The kynurenine pathway and the brain: challenges, controversies and promises","volume":"112","author":"Schwarcz","year":"2017","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.phymed.2026.158679_bib0023","doi-asserted-by":"crossref","first-page":"3764","DOI":"10.1093\/brain\/awae143","article-title":"Hippocampal excitation-inhibition balance underlies the 5-HT2C receptor in modulating depressive behaviours","volume":"147","author":"Shi","year":"2024","journal-title":"Brain"},{"key":"10.1016\/j.phymed.2026.158679_bib0024","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1002\/ame2.70095","article-title":"Antiviral and immunomodulatory effects of Chaihu Guizhi decoction in an acute depression-like mouse model infected with influenza A virus","volume":"8","author":"Shi","year":"2025","journal-title":"Anim. Models Exp. Med."},{"key":"10.1016\/j.phymed.2026.158679_bib0025","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1038\/s41380-018-0053-1","article-title":"Synaptic phospholipids as a new target for cortical hyperexcitability and E\/I balance in psychiatric disorders","volume":"23","author":"Thalman","year":"2018","journal-title":"Mol. Psychiatr."},{"key":"10.1016\/j.phymed.2026.158679_bib0026","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1007\/s12035-020-02181-0","article-title":"Neonatal serotonin depletion induces hyperactivity and anxiolytic-like sex-dependent effects in adult rats","volume":"58","author":"Trujillo","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.phymed.2026.158679_bib0027","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.2147\/NDT.S377982","article-title":"KXS Balances the tryptophan metabolism in mild to moderate depressed patients and chronic restraint stress induced depressive rats","volume":"18","author":"Wang","year":"2022","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"10.1016\/j.phymed.2026.158679_bib0028","article-title":"Basolateral amygdala serotonin 2C receptor regulates emotional disorder-related symptoms induced by chronic methamphetamine administration","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.phymed.2026.158679_bib0029","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3389\/fncel.2020.00082","article-title":"The role of BDNF on neural plasticity in depression","volume":"14","author":"Yang","year":"2020","journal-title":"Front. Cell Neurosci."},{"key":"10.1016\/j.phymed.2026.158679_bib0030","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2025.157029","article-title":"Anxiolytic effects of corilagin by targeting Htr2c through activation of the TrkB\/CREB\/BDNF pathway","volume":"145","author":"Yun","year":"2025","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2026.158679_bib0031","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.biopsych.2018.06.019","article-title":"Chronic stress remodels synapses in an amygdala circuit-specific manner","volume":"85","author":"Zhang","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.phymed.2026.158679_bib0032","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.118806","article-title":"Chaihu Guizhi Decoction prevents cognitive, memory impairments and sensorimotor gating deficit induced by N-methyl-d-aspartate receptor antibody in mice","volume":"337","author":"Zhu","year":"2025","journal-title":"J. Ethnopharmacol."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711326009116?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711326009116?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:29:19Z","timestamp":1787552959000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711326009116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":32,"alternative-id":["S0944711326009116"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2026.158679","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Chaihu-Guizhi Decoction and Saikosaponin D alleviate anxiety-like behavior by engaging HTR2C-related neurotrophic and excitatory synaptic homeostasis","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2026.158679","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier GmbH. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"158679"}}