{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T07:20:01Z","timestamp":1787556001099,"version":"build-2736575974"},"reference-count":91,"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\/501100018531","name":"Major Science and Technology Projects in Yunnan Province","doi-asserted-by":"publisher","award":["202202AG050008"],"award-info":[{"award-number":["202202AG050008"]}],"id":[{"id":"10.13039\/501100018531","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82,160,787"],"award-info":[{"award-number":["82,160,787"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32,160,157"],"award-info":[{"award-number":["32,160,157"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010971","name":"People's Government of Yunnan Province","doi-asserted-by":"publisher","award":["CA24129L025A"],"award-info":[{"award-number":["CA24129L025A"]}],"id":[{"id":"10.13039\/501100010971","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010971","name":"People's Government of Yunnan Province","doi-asserted-by":"publisher","award":["YNWR-QNBJ-2020-247"],"award-info":[{"award-number":["YNWR-QNBJ-2020-247"]}],"id":[{"id":"10.13039\/501100010971","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007846","name":"Yunnan Province Department of Education","doi-asserted-by":"publisher","award":["2025J0272"],"award-info":[{"award-number":["2025J0272"]}],"id":[{"id":"10.13039\/501100007846","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.2026.158697","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T16:28:41Z","timestamp":1786033721000},"page":"158697","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Otophylloside T alleviates depression-like behaviors by directly targeting EP4: An integrated multi-strategy study"],"prefix":"10.1016","volume":"160","author":[{"given":"Hao","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Li","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Zhong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Rui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2026.158697_bib0001","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2021.753279","article-title":"Luteolin modulates neural stem cells fate determination: in vitro study on human neural stem cells, and in vivo study on LPS-induced depression mice model","volume":"9","author":"Achour","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.phymed.2026.158697_bib0002","doi-asserted-by":"crossref","DOI":"10.1016\/j.psychres.2025.116575","article-title":"Targeting of inflammation and prostaglandins by nonsteroidal anti-inflammatory drugs in schizophrenia: a narrative review","volume":"351","author":"Al-kuraishy","year":"2025","journal-title":"Psychiatry Res."},{"key":"10.1016\/j.phymed.2026.158697_bib0003","doi-asserted-by":"crossref","DOI":"10.1111\/jpi.12667","article-title":"Melatonin prevents neuroinflammation and relieves depression by attenuating autophagy impairment through FOXO3a regulation","volume":"69","author":"Ali","year":"2020","journal-title":"J. Pineal Res."},{"key":"10.1016\/j.phymed.2026.158697_bib0004","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2407130121","article-title":"SPMs exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin EP4 receptor","volume":"121","author":"Alnouri","year":"2024","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.phymed.2026.158697_bib0005","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.prostaglandins.2009.04.003","article-title":"Emerging roles of PGE2 receptors in models of neurological disease","volume":"91","author":"Andreasson","year":"2010","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"10.1016\/j.phymed.2026.158697_bib0006","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.bbr.2018.05.016","article-title":"Chronic unpredictable mild stress-induced depressive-like behavior and dysregulation of brain levels of biogenic amines in Drosophila melanogaster","volume":"351","author":"Araujo","year":"2018","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.phymed.2026.158697_bib0007","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2020.114147","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective","volume":"180","author":"Bindu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0008","doi-asserted-by":"crossref","DOI":"10.1016\/j.cptl.2025.102460","article-title":"Logistic regression modeling: methodological insights and roadmap","volume":"17","author":"Bui","year":"2025","journal-title":"Curr. Pharm. Teach. Learn."},{"key":"10.1016\/j.phymed.2026.158697_bib0009","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1038\/s41589-024-01679-1","article-title":"Machine learning in preclinical drug discovery","volume":"20","author":"Catacutan","year":"2024","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.phymed.2026.158697_bib0010","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2025.107654","article-title":"Gut microbiome-derived indole-3-carboxaldehyde regulates stress vulnerability in chronic restraint stress by activating aryl hydrocarbon receptors","volume":"213","author":"Chen","year":"2025","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.phymed.2026.158697_bib0011","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2026.158487","article-title":"Multi-strategy investigation identifies amentoflavone as a novel D3R antagonist for Parkinson's disease treatment","volume":"159","author":"Chen","year":"2026","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2026.158697_bib0012","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.eng.2023.09.011","article-title":"The application of artificial intelligence accelerates G protein-coupled receptor ligand discovery","volume":"32","author":"Chen","year":"2024","journal-title":"Engineering"},{"key":"10.1016\/j.phymed.2026.158697_bib0013","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108400","article-title":"Discovery and characterization of novel FAK inhibitors for breast cancer therapy via hybrid virtual screening, biological evaluation and molecular dynamics simulations","volume":"159","author":"Chi","year":"2025","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.phymed.2026.158697_bib0014","doi-asserted-by":"crossref","first-page":"5563","DOI":"10.1038\/s41380-025-03118-6","article-title":"Gene expression signatures of response to fluoxetine treatment: systematic review and meta-analyses","volume":"30","author":"Cooper","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.phymed.2026.158697_bib0015","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.drudis.2021.09.007","article-title":"Machine-learning methods for ligand\u2013protein molecular docking","volume":"27","author":"Crampon","year":"2022","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.phymed.2026.158697_bib0016","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41392-024-01738-y","article-title":"Major depressive disorder: hypothesis, mechanism, prevention and treatment","volume":"9","author":"Cui","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.phymed.2026.158697_bib0017","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.3390\/s23042085","article-title":"Bayesian optimization with support vector machine model for Parkinson disease classification","volume":"23","author":"Elshewey","year":"2023","journal-title":"Sensors"},{"key":"10.1016\/j.phymed.2026.158697_bib0018","doi-asserted-by":"crossref","first-page":"8067","DOI":"10.1038\/s41467-023-43506-6","article-title":"Docking for EP4R antagonists active against inflammatory pain","volume":"14","author":"Gahbauer","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.phymed.2026.158697_bib0019","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2024.116481","article-title":"The emergence of antidepressant drugs targeting GABAA receptors: a concise review","volume":"228","author":"Gonda","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0020","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1124\/mol.113.087072","article-title":"Fluorescence correlation spectroscopy analysis of serotonin, adrenergic, muscarinic, and dopamine receptor dimerization: the oligomer number puzzle","volume":"84","author":"Herrick-Davis","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0021","doi-asserted-by":"crossref","DOI":"10.1016\/j.jpha.2024.101157","article-title":"The integration of machine learning into traditional Chinese medicine","volume":"15","author":"Hong","year":"2025","journal-title":"J. Pharm. Anal."},{"key":"10.1016\/j.phymed.2026.158697_bib0022","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1214\/aos\/1013203450","article-title":"Greedy function approximation: a gradient boosting machine","volume":"29","author":"Jerome","year":"2001","journal-title":"Ann. Stat."},{"key":"10.1016\/j.phymed.2026.158697_bib0023","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1007\/s11030-025-11216-4","article-title":"Enhancing PI3K\u03b3 inhibitor discovery: a machine learning-based virtual screening approach integrating pharmacophores, docking, and molecular descriptors","volume":"29","author":"Jia","year":"2025","journal-title":"Mol. Divers."},{"key":"10.1016\/j.phymed.2026.158697_bib0024","article-title":"Inhibition of the prostaglandin EP2 receptor prevents long-term cognitive impairment in a model of systemic inflammation","volume":"8","author":"Jiang","year":"2020","journal-title":"Brain Behav. Immun. Health"},{"key":"10.1016\/j.phymed.2026.158697_bib0025","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1186\/s12888-025-06848-7","article-title":"A review of the 257 meta-analyses of the differences between females and males in prevalence and risk, protective factors, and treatment outcomes for mental disorder","volume":"25","author":"Kayrouz","year":"2025","journal-title":"BMC Psychiatry"},{"key":"10.1016\/j.phymed.2026.158697_bib0026","series-title":"The Mouse Brain in Stereotaxic coordinates, Compact","author":"Franklin","year":"2019"},{"key":"10.1016\/j.phymed.2026.158697_bib0027","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev. Dyn."},{"key":"10.1016\/j.phymed.2026.158697_bib0028","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/ar000033j","article-title":"Calculating structures and free energies of complex molecules:\u2009 combining molecular mechanics and continuum models","volume":"33","author":"Kollman","year":"2000","journal-title":"Acc. Chem. Res."},{"key":"10.1016\/j.phymed.2026.158697_bib0029","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.pharmthera.2013.03.006","article-title":"E-type prostanoid receptor 4 (EP4) in disease and therapy","volume":"138","author":"Konya","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.phymed.2026.158697_bib0030","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s11481-023-10083-w","article-title":"PPAR\u0251 ligand caudatin improves cognitive functions and mitigates Alzheimer\u2019s disease defects by inducing autophagy in mice models","volume":"18","author":"Krishnamoorthi","year":"2023","journal-title":"J. Neuroimmune Pharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0031","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.jare.2024.10.016","article-title":"Panaxatriol exerts anti-senescence effects and alleviates osteoarthritis and cartilage repair fibrosis by targeting UFL1","volume":"74","author":"Kuang","year":"2025","journal-title":"J. Adv. Res."},{"key":"10.1016\/j.phymed.2026.158697_bib0032","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S0140-6736(11)60602-8","article-title":"Major depressive disorder: new clinical, neurobiological, and treatment perspectives","volume":"379","author":"Kupfer","year":"2012","journal-title":"Lancet"},{"key":"10.1016\/j.phymed.2026.158697_bib0033","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1159\/000350094","article-title":"Molecular mechanisms of depression: perspectives on new treatment strategies","volume":"31","author":"Lang","year":"2013","journal-title":"Cell. Physiol. Biochem."},{"key":"10.1016\/j.phymed.2026.158697_bib0034","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13321-016-0158-y","article-title":"Rocker: open source, easy-to-use tool for AUC and enrichment calculations and ROC visualization","volume":"8","author":"L\u00e4tti","year":"2016","journal-title":"J. Cheminf."},{"key":"10.1016\/j.phymed.2026.158697_bib0035","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1126\/science.1109237","article-title":"Transduction of receptor signals by \u03b2-arrestins","volume":"308","author":"Lefkowitz","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.phymed.2026.158697_bib0036","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1021\/np501058b","article-title":"Bioactive C21 steroidal glycosides from the roots of Cynanchum otophyllum that suppress the seizure-like locomotor activity of zebrafish caused by pentylenetetrazole","volume":"78","author":"Li","year":"2015","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.phymed.2026.158697_bib0037","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1080\/10286020.2014.1001380","article-title":"Antiepileptic C21 steroids from the roots of Cynanchum otophyllum","volume":"17","author":"Li","year":"2015","journal-title":"J. Asian Nat. Prod. Res."},{"key":"10.1016\/j.phymed.2026.158697_bib0038","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.bbi.2024.04.036","article-title":"BGP-15 alleviates LPS-induced depression-like behavior by promoting mitophagy","volume":"119","author":"Liu","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.phymed.2026.158697_bib0039","doi-asserted-by":"crossref","first-page":"21984","DOI":"10.1073\/pnas.0910040106","article-title":"Target identification using drug affinity responsive target stability (DARTS)","volume":"106","author":"Lomenick","year":"2009","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.phymed.2026.158697_bib0040","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0293266","article-title":"EFFNet: a skin cancer classification model based on feature fusion and random forests","volume":"18","author":"Ma","year":"2023","journal-title":"PLoS ONE"},{"key":"10.1016\/j.phymed.2026.158697_bib0041","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1126\/science.abb6748","article-title":"Enhanced ERK activity extends ketamine's antidepressant effects by augmenting synaptic plasticity","volume":"388","author":"Ma","year":"2025","journal-title":"Science"},{"key":"10.1016\/j.phymed.2026.158697_bib0042","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1292\/jvms.25-0196","article-title":"Prostaglandin F(2\u03b1) exacerbates ovalbumin-induced chronic pneumonia and attenuates depression in mice","volume":"87","author":"Maehara","year":"2025","journal-title":"J. Vet. Med. Sci."},{"key":"10.1016\/j.phymed.2026.158697_bib0043","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1038\/s41467-023-38530-5","article-title":"Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes","volume":"14","author":"Maitra","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.phymed.2026.158697_bib0044","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi","year":"2018","journal-title":"Lancet."},{"key":"10.1016\/j.phymed.2026.158697_bib0045","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.neuroscience.2015.04.047","article-title":"Hippocampal neuroplasticity in major depressive disorder","volume":"309","author":"Malykhin","year":"2015","journal-title":"Neuroscience"},{"key":"10.1016\/j.phymed.2026.158697_bib0046","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41380-021-01040-1","article-title":"Update on GPCR-based targets for the development of novel antidepressants","volume":"27","author":"Mantas","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.phymed.2026.158697_bib0047","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.biopsych.2008.11.029","article-title":"Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression","volume":"65","author":"Miller","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.phymed.2026.158697_bib0048","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.1233606","article-title":"Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay","volume":"341","author":"Molina","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.phymed.2026.158697_bib0049","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.117982","article-title":"Therapeutic potential of CB1R activation by Qingyangshen glycoside M1 for seizure relief","volume":"327","author":"Mu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0050","doi-asserted-by":"crossref","first-page":"6582","DOI":"10.1021\/jm300687e","article-title":"Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking","volume":"55","author":"Mysinger","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.phymed.2026.158697_bib0051","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/s41593-020-0621-y","article-title":"Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons","volume":"23","author":"Nagy","year":"2020","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.phymed.2026.158697_bib0052","doi-asserted-by":"crossref","DOI":"10.3791\/55737","article-title":"The optical fractionator technique to estimate cell numbers in a rat model of electroconvulsive therapy","author":"Olesen","year":"2017","journal-title":"J. Vis. Exp."},{"key":"10.1016\/j.phymed.2026.158697_bib0053","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1021\/acs.analchem.3c03341","article-title":"Fluorescence correlation spectroscopy as a versatile method to define aptamer\u2013protein interactions with single-molecule sensitivity","volume":"96","author":"Porciani","year":"2024","journal-title":"Anal. Chem."},{"key":"10.1016\/j.phymed.2026.158697_bib0054","doi-asserted-by":"crossref","first-page":"374","DOI":"10.3390\/ijms25010374","article-title":"Single-molecule imaging reveals differential AT1R stoichiometry change in biased signaling","volume":"25","author":"Qin","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phymed.2026.158697_bib0055","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1021\/ci700157b","article-title":"y-randomization and its variants in QSPR\/QSAR","volume":"47","author":"R\u00fccker","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.phymed.2026.158697_bib0056","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1176\/ajp.2007.164.2.201","article-title":"STARD: what have we learned?","volume":"164","author":"Rush","year":"2007","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.phymed.2026.158697_bib0057","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.pnpbp.2004.11.003","article-title":"Cytokines and major depression","volume":"29","author":"Schiepers","year":"2005","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.phymed.2026.158697_bib0058","doi-asserted-by":"crossref","first-page":"674","DOI":"10.2174\/1570159X14666160115130414","article-title":"Inflammation and immune regulation as potential drug targets in antidepressant treatment","volume":"14","author":"Schmidt","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0059","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/mp.2010.52","article-title":"Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression","volume":"16","author":"Shelton","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.phymed.2026.158697_bib0060","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.phytol.2014.04.017","article-title":"Four new C21 steroidal glycosides from Cynanchum otophyllum Schneid","volume":"9","author":"Shen","year":"2014","journal-title":"Phytochem. Lett."},{"key":"10.1016\/j.phymed.2026.158697_bib0061","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2016.00224","article-title":"Protective effects of otophylloside N on pentylenetetrazol-induced neuronal injury in vitro and in vivo","volume":"7","author":"Sheng","year":"2016","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0062","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2016.00224","article-title":"Protective effects of otophylloside N on pentylenetetrazol-induced neuronal injury In vitro and In vivo","volume":"7","author":"Sheng","year":"2016","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0063","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.4049\/jimmunol.0903487","article-title":"The prostaglandin E2 E-prostanoid 4 receptor exerts anti-inflammatory effects in brain innate immunity","volume":"184","author":"Shi","year":"2010","journal-title":"J. Immunol."},{"key":"10.1016\/j.phymed.2026.158697_bib0064","first-page":"733","article-title":"Aspirin fails to prevent depression in older adults","volume":"324","author":"Slomski","year":"2020","journal-title":"JAMA"},{"key":"10.1016\/j.phymed.2026.158697_bib0065","doi-asserted-by":"crossref","first-page":"P107","DOI":"10.1016\/j.jalz.2018.06.2194","article-title":"Impact of brain section sampling on statistical power of adult hippocampal neurogenesis rate estimates in mouse brain","volume":"14","author":"Smith","year":"2018","journal-title":"Alzheimer's Dement."},{"key":"10.1016\/j.phymed.2026.158697_bib0066","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.2174\/1570180819666220819102035","article-title":"Predicting binding affinity between MHC-I receptor and peptides based on molecular docking and protein-peptide interaction interface characteristics","volume":"20","author":"Songtao","year":"2023","journal-title":"Lett. Drug Des. Discov."},{"key":"10.1016\/j.phymed.2026.158697_bib0067","doi-asserted-by":"crossref","first-page":"11613","DOI":"10.1074\/jbc.R600038200","article-title":"Prostaglandin E receptors","volume":"282","author":"Sugimoto","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.phymed.2026.158697_bib0068","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s12974-020-01843-z","article-title":"Extrasynaptic CaMKII\u03b1 is involved in the antidepressant effects of ketamine by downregulating GluN2B receptors in an LPS-induced depression model","volume":"17","author":"Tang","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.phymed.2026.158697_bib0069","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ymeth.2023.06.012","article-title":"A multi-platform normalization method for meta-analysis of gene expression data","volume":"217","author":"Tihagam","year":"2023","journal-title":"Methods"},{"key":"10.1016\/j.phymed.2026.158697_bib0070","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41589-018-0131-3","article-title":"Ligand binding to human prostaglandin E receptor EP4 at the lipid-bilayer interface","volume":"15","author":"Toyoda","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.phymed.2026.158697_bib0071","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.phymed.2026.158697_bib0072","doi-asserted-by":"crossref","first-page":"5342","DOI":"10.1109\/IEMBS.2006.260118","article-title":"Classifying ovarian tumors using bayesian multi-layer perceptrons and automatic relevance determination: a multi-center study","volume":"2006","author":"Van Calster","year":"2006","journal-title":"Conf. Proc. IEEE Eng. Med. Biol. Soc."},{"key":"10.1016\/j.phymed.2026.158697_bib0073","doi-asserted-by":"crossref","first-page":"e193","DOI":"10.1002\/gps.4767","article-title":"Aspirin and incident depressive symptoms: a longitudinal cohort study over 8 years","volume":"33","author":"Veronese","year":"2018","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"10.1016\/j.phymed.2026.158697_bib0074","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/s12964-024-01691-x","article-title":"A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo","volume":"22","author":"Wakasugi","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"10.1016\/j.phymed.2026.158697_bib0075","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/ame2.12499","article-title":"Effects of Qingyangshen glycosides on neuroplasticity in a mouse model of social defeat","volume":"8","author":"Wang","year":"2025","journal-title":"Anim. Models Exp. Med."},{"key":"10.1016\/j.phymed.2026.158697_bib0076","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2026.104154","article-title":"Synaptojanin-2-binding protein ameliorates oxidative stress, neuroinflammation and depression-like behaviors via SYNJ2\/PIP2\/IP3 signaling pathway","volume":"93","author":"Wang","year":"2026","journal-title":"Redox Biol."},{"key":"10.1016\/j.phymed.2026.158697_bib0077","article-title":"Efficacy of inflammation-based stratification for add-on celecoxib or minocycline in major depressive disorder: protocol of the INSTA-MD double-blind placebo-controlled randomised clinical trial","volume":"41","author":"Wessa","year":"2024","journal-title":"Brain Behav. Immun. Health"},{"key":"10.1016\/j.phymed.2026.158697_bib0078","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1021\/acs.jcim.0c00291","article-title":"NetInfer: a web server for prediction of targets and therapeutic and adverse effects via network-based inference methods","volume":"60","author":"Wu","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.phymed.2026.158697_bib0079","doi-asserted-by":"crossref","DOI":"10.1016\/j.xpro.2023.102761","article-title":"Protocol for lentivirus-mediated delivery of genes to study neurogenesis and cognitive function in adult rodents","volume":"4","author":"Xu","year":"2023","journal-title":"STAR Protoc."},{"key":"10.1016\/j.phymed.2026.158697_bib0080","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2025.110362","article-title":"Esketamine mitigates endotoxin-induced hippocampal injury by regulating calcium transient and synaptic plasticity via the NF-\u03b11\/CREB pathway","volume":"269","author":"Xu","year":"2025","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.phymed.2026.158697_bib0081","doi-asserted-by":"crossref","first-page":"14937","DOI":"10.1074\/jbc.M111.334300","article-title":"Intramolecular fluorescence resonance energy transfer (FRET) sensors of the orexin OX1 and OX2 receptors identify slow kinetics of agonist activation","volume":"287","author":"Xu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.phymed.2026.158697_bib0082","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s13659-017-0122-1","article-title":"Otophylloside B protects against A\u03b2 toxicity in caenorhabditis elegans models of Alzheimer\u2019s disease","volume":"7","author":"Yang","year":"2017","journal-title":"Nat. Prod. Bioprospect."},{"key":"10.1016\/j.phymed.2026.158697_bib0083","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2025.119643","article-title":"Integrative investigation on the mechanisms of modified Zuojin Pill (SQQT) in ameliorating gastric metaplasia","volume":"346","author":"Yang","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0084","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2021.114864","article-title":"Dictamnine, a novel c-met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K\/AKT\/mTOR and MAPK signaling pathways","volume":"195","author":"Yu","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0085","doi-asserted-by":"crossref","DOI":"10.3389\/fphy.2021.644450","article-title":"A comprehensive review of fluorescence correlation spectroscopy","volume":"9","author":"Yu","year":"2021","journal-title":"Front. Phys."},{"key":"10.1016\/j.phymed.2026.158697_bib0086","doi-asserted-by":"crossref","DOI":"10.1111\/jpi.70016","article-title":"Activation of the melatonin receptor MT(1) by the natural product Gastrodin to promote sleep","volume":"76","author":"Zhang","year":"2024","journal-title":"J. Pineal Res."},{"key":"10.1016\/j.phymed.2026.158697_bib0087","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2025.177498","article-title":"Parishin A alleviates insomnia by regulating hypothalamic-pituitary-adrenal axis homeostasis and directly targeting orexin receptor OX2","volume":"998","author":"Zhang","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.phymed.2026.158697_bib0088","doi-asserted-by":"crossref","first-page":"9505","DOI":"10.3390\/ijms22179505","article-title":"A reliable high-throughput screening model for antidepressant","volume":"22","author":"Zhang","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phymed.2026.158697_bib0089","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1021\/acs.analchem.9b04531","article-title":"Solvent-induced protein precipitation for drug target discovery on the proteomic scale","volume":"92","author":"Zhang","year":"2020","journal-title":"Anal. Chem."},{"key":"10.1016\/j.phymed.2026.158697_bib0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2024.107566","article-title":"New insights into anti-depression effects of bioactive phytochemicals","volume":"212","author":"Zhao","year":"2025","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.phymed.2026.158697_bib0091","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/S1473-3099(20)30276-0","article-title":"Interferon-\u03b3 release assays or tuberculin skin test for detection and management of latent tuberculosis infection: a systematic review and meta-analysis","volume":"20","author":"Zhou","year":"2020","journal-title":"Lancet Infect. Dis."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711326009293?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711326009293?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:28:19Z","timestamp":1787552899000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711326009293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":91,"alternative-id":["S0944711326009293"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2026.158697","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":"Otophylloside T alleviates depression-like behaviors by directly targeting EP4: An integrated multi-strategy study","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2026.158697","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":"158697"}}