{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:25:29Z","timestamp":1793917529570,"version":"4.8.0"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2024KY055"],"award-info":[{"award-number":["2024KY055"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008867","name":"Department of Education of Zhejiang Province","doi-asserted-by":"publisher","award":["KYYB202010"],"award-info":[{"award-number":["KYYB202010"]}],"id":[{"id":"10.13039\/501100008867","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Zhejiang Province Natural Science Foundation","doi-asserted-by":"publisher","award":["LQ23H090018"],"award-info":[{"award-number":["LQ23H090018"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.taap.2026.118064","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:07:50Z","timestamp":1790687270000},"page":"118064","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Tuberostemonine produces antidepressant effects via the BDNF\/TrkB\/Erk\/CREB signaling pathway"],"prefix":"10.1016","volume":"517","author":[{"given":"Fan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyao","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurui","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houming","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2026.118064_bb0005","doi-asserted-by":"crossref","first-page":"15788","DOI":"10.1073\/pnas.0406960101","article-title":"Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor","volume":"101","author":"Aicardi","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.taap.2026.118064_bb0010","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.biopsych.2005.11.003","article-title":"The role of CREB in depression and antidepressant treatment","volume":"59","author":"Blendy","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0015","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1176\/ajp.157.1.115","article-title":"Hippocampal volume reduction in major depression","volume":"157","author":"Bremner","year":"2000","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0020","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biopsych.2021.05.008","article-title":"Brain-derived neurotrophic factor signaling in depression and antidepressant action","volume":"90","author":"Castr\u00e9n","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155452","article-title":"Natural product Kaji-ichigoside F1 exhibits rapid antidepression via activating the AMPA\u2013BDNF\u2013mTOR pathway and inhibiting the NMDAR\u2013CaMKII\u03b1 pathway","volume":"126","author":"Chen","year":"2024","journal-title":"Phytomedicine"},{"key":"10.1016\/j.taap.2026.118064_bb0030","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/S2215-0366(20)30036-5","article-title":"Treatment outcomes for depression: challenges and opportunities","volume":"7","author":"Cuijpers","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0035","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.phrs.2009.09.008","article-title":"PD98059, a specific MAP kinase inhibitor, attenuates multiple organ dysfunction syndrome\/failure (MODS) induced by zymosan in mice","volume":"61","author":"Di Paola","year":"2010","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.taap.2026.118064_bb0040","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1126\/science.1222939","article-title":"Synaptic dysfunction in depression: potential therapeutic targets","volume":"338","author":"Duman","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.taap.2026.118064_bb0045","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3390\/neurolint13030038","article-title":"Selective serotonin reuptake inhibitors and adverse effects: a narrative review","volume":"13","author":"Edinoff","year":"2021","journal-title":"Neurol. Int."},{"key":"10.1016\/j.taap.2026.118064_bb0050","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/s41380-022-01806-1","article-title":"Molecular pathways of major depressive disorder converge on the synapse","volume":"28","author":"Fries","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0055","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1126\/science.7907431","article-title":"Requirement for BDNF in activity-dependent survival of cortical neurons","volume":"263","author":"Ghosh","year":"1994","journal-title":"Science"},{"key":"10.1016\/j.taap.2026.118064_bb0060","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd4510","article-title":"The re-emergence of natural products for drug discovery in the genomics era","volume":"14","author":"Harvey","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.taap.2026.118064_bb0065","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1001\/jamapsychiatry.2021.4313","article-title":"Combining antidepressants vs antidepressant monotherapy for treatment of patients with acute depression: a systematic review and meta-analysis","volume":"79","author":"Henssler","year":"2022","journal-title":"JAMA Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0070","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1038\/nn927","article-title":"BDNF release from single cells elicits local dendritic growth in nearby neurons","volume":"5","author":"Horch","year":"2002","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.taap.2026.118064_bb0075","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ejphar.2016.02.006","article-title":"The therapeutic effects of tuberostemonine against cigarette smoke-induced acute lung inflammation in mice","volume":"774","author":"Jung","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.taap.2026.118064_bb0080","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.1078548","article-title":"Natural products as an emerging therapeutic alternative for the treatment of anxiety and depression, volume II","volume":"13","author":"Khan","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.taap.2026.118064_bb0085","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1056\/NEJMp1903305","article-title":"Esketamine for treatment-resistant depression\u2014first FDA-approved antidepressant in a new class","volume":"381","author":"Kim","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.taap.2026.118064_bb0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.cbi.2023.110545","article-title":"Tuberostemonine alleviates high-fat diet-induced obesity and hepatic steatosis by increasing energy consumption","volume":"381","author":"Li","year":"2023","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.taap.2026.118064_bb0095","article-title":"Tuberostemonine ameliorates Alzheimer\u2018s disease pathology by suppression of the p38 MAPK signaling pathway","volume":"29","author":"Li","year":"2026","journal-title":"iScience"},{"key":"10.1016\/j.taap.2026.118064_bb0100","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.116983","article-title":"Tuberostemonine may enhance the function of the SLC7A11\/glutamate antiporter to restrain the ferroptosis to alleviate pulmonary fibrosis","volume":"318","author":"Liu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.taap.2026.118064_bb0105","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0140-6736(22)02080-3","article-title":"Novel and emerging treatments for major depression","volume":"401","author":"Marwaha","year":"2023","journal-title":"Lancet"},{"key":"10.1016\/j.taap.2026.118064_bb0110","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1176\/appi.ajp.2020.20081251","article-title":"Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation","volume":"178","author":"McIntyre","year":"2021","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0115","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/wps.21120","article-title":"Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions","volume":"22","author":"McIntyre","year":"2023","journal-title":"World Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0120","doi-asserted-by":"crossref","first-page":"904","DOI":"10.2174\/1570159X21666230811141557","article-title":"The HPA axis as target for depression","volume":"22","author":"Menke","year":"2024","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.taap.2026.118064_bb0125","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/mp.2013.105","article-title":"Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484)","volume":"19","author":"Molendijk","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0130","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tins.2008.06.006","article-title":"The HPA axis in major depression: classical theories and new developments","volume":"31","author":"Pariante","year":"2008","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.taap.2026.118064_bb0135","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.euroneuro.2023.08.496","article-title":"Sucrose preference test: a systematic review of protocols for the assessment of anhedonia in rodents","volume":"77","author":"Primo","year":"2023","journal-title":"Eur. Neuropsychopharmacol."},{"key":"10.1016\/j.taap.2026.118064_bb0140","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ynstr.2015.12.005","article-title":"Corticosterone exposure augments sensitivity to the behavioral and neuroplastic effects of fluoxetine in C57BL\/6 mice","volume":"3","author":"Robinson","year":"2016","journal-title":"Neurobiol. Stress"},{"key":"10.1016\/j.taap.2026.118064_bb0145","doi-asserted-by":"crossref","DOI":"10.3390\/nu14163314","article-title":"Luteolin-7-O-glucuronide improves depression-like and stress coping behaviors in sleep deprivation stress model by activation of the BDNF signaling","volume":"14","author":"Ryu","year":"2022","journal-title":"Nutrients"},{"key":"10.1016\/j.taap.2026.118064_bb0150","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/S0140-6736(21)02143-7","article-title":"Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic","volume":"398","author":"Santomauro","year":"2021","journal-title":"Lancet"},{"key":"10.1016\/j.taap.2026.118064_bb0155","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1749-6632.2012.06633.x","article-title":"Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction","volume":"1261","author":"Silverman","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.taap.2026.118064_bb0160","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.biopsych.2004.08.022","article-title":"Cellular changes in the postmortem hippocampus in major depression","volume":"56","author":"Stockmeier","year":"2004","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0165","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainres.2023.148678","article-title":"Sex differences in a corticosterone-induced depression model in mice: behavioral, neurochemical, and molecular insights","volume":"1823","author":"Tao","year":"2024","journal-title":"Brain Res."},{"key":"10.1016\/j.taap.2026.118064_bb0170","doi-asserted-by":"crossref","first-page":"6197","DOI":"10.1007\/s12035-019-1524-3","article-title":"The ERK pathway: molecular mechanisms and treatment of depression","volume":"56","author":"Wang","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.taap.2026.118064_bb0175","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cell.2021.12.003","article-title":"BDNF signaling in context: from synaptic regulation to psychiatric disorders","volume":"185","author":"Wang","year":"2022","journal-title":"Cell"},{"key":"10.1016\/j.taap.2026.118064_bb0180","author":"World Health Organization"},{"key":"10.1016\/j.taap.2026.118064_bb0185","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1080\/15622975.2023.2279958","article-title":"Repetitive transcranial magnetic stimulation and fluoxetine attenuate astroglial activation and benefit behaviours in a chronic unpredictable mild stress mouse model of depression","volume":"25","author":"Yuan","year":"2023","journal-title":"World J. Biol. Psychiatry"},{"key":"10.1016\/j.taap.2026.118064_bb0190","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2020.107686","article-title":"The strategies and techniques of drug discovery from natural products","volume":"216","author":"Zhang","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.taap.2026.118064_bb0195","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.7150\/thno.81067","article-title":"Hyperactive neuronal autophagy depletes BDNF and impairs adult hippocampal neurogenesis in a corticosterone-induced mouse model of depression","volume":"13","author":"Zhang","year":"2023","journal-title":"Theranostics"},{"key":"10.1016\/j.taap.2026.118064_bb0200","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155729","article-title":"Molecular mechanism of Chang Shen Hua volatile oil modulating brain cAMP-PKA-CREB pathway to improve depression-like behavior in rats","volume":"130","author":"Zhang","year":"2024","journal-title":"Phytomedicine"}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X26003601?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X26003601?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:48:06Z","timestamp":1793915286000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X26003601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":40,"alternative-id":["S0041008X26003601"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2026.118064","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Tuberostemonine produces antidepressant effects via the BDNF\/TrkB\/Erk\/CREB signaling pathway","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2026.118064","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118064"}}