{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T12:30:38Z","timestamp":1793795438437,"version":"4.6.1"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2027,2]]},"DOI":"10.1016\/j.jep.2026.122472","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:13:09Z","timestamp":1791846789000},"page":"122472","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"P3","title":["Modified Danzhi Xiaoyao San ameliorates depression-associated dry eye by modulating sphingolipid metabolism across the liver, hippocampus, and lacrimal gland"],"prefix":"10.1016","volume":"374","author":[{"given":"Yan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1757-3899","authenticated-orcid":false,"given":"Qibo","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5315-0336","authenticated-orcid":false,"given":"Yuxi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9175-526X","authenticated-orcid":false,"given":"Shuaishuai","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3072-4515","authenticated-orcid":false,"given":"Zhiying","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"11","key":"10.1016\/j.jep.2026.122472_bib1","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1194\/jlr.M026732","article-title":"Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2","volume":"53","author":"Alexandra","year":"2012","journal-title":"J. Lipid Res."},{"issue":"4","key":"10.1016\/j.jep.2026.122472_bib2","article-title":"Dry eye disease and psychiatric disorders: a systematic review and meta-analysis","volume":"32","author":"Amy","year":"2021","journal-title":"Eur. J. Ophthalmol."},{"key":"10.1016\/j.jep.2026.122472_bib3","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jare.2024.03.015","article-title":"Decoding and reconstructing disease relations between dry eye and depression: a multimodal investigation comprising meta-analysis, genetic pathways and Mendelian randomization","volume":"69","author":"Chang","year":"2025","journal-title":"J. Adv. Res."},{"issue":"4","key":"10.1016\/j.jep.2026.122472_bib4","first-page":"1025","article-title":"A brief analysis of the treatment of dry eye in \"Examining the Yao Letters\"","volume":"30","author":"Chen","year":"2019","journal-title":"Lishizhen Med. Mater. Medica Res."},{"issue":"2","key":"10.1016\/j.jep.2026.122472_bib5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1167\/iovs.67.2.58","article-title":"Ly93 inhibits sphingomyelin synthesis and attenuates inflammation and injury in dry eye conjunctival organoids","volume":"67","author":"Chen","year":"2026","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.jep.2026.122472_bib6","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2024.1307682","article-title":"Inflammation mechanism and anti-inflammatory therapy of dry eye","volume":"11","author":"Chu","year":"2024","journal-title":"Front. Med."},{"issue":"9","key":"10.1016\/j.jep.2026.122472_bib7","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s00592-018-1173-4","article-title":"The response of serum Glypican-4 levels and its potential regulatory mechanism to endurance training and chamomile flowers' hydroethanolic extract in streptozotocin-nicotinamide-induced diabetic rats","volume":"55","author":"Farzad","year":"2018","journal-title":"Acta Diabetol."},{"issue":"1","key":"10.1016\/j.jep.2026.122472_bib8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13098-020-00553-z","article-title":"Endurance exercise training restores diabetes-induced alteration in circulating Glycosylphosphatidylinositol-specific phospholipase D levels in rats","volume":"12","author":"Farzad","year":"2020","journal-title":"Diabetol. Metab. Syndr."},{"issue":"5","key":"10.1016\/j.jep.2026.122472_bib9","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.cmet.2026.04.002","article-title":"Exerkine GPLD1 bridges liver and brain","volume":"38","author":"Florido","year":"2026","journal-title":"Cell Metab."},{"issue":"1","key":"10.1016\/j.jep.2026.122472_bib10","doi-asserted-by":"crossref","DOI":"10.1038\/s41380-022-01806-1","article-title":"Molecular pathways of major depressive disorder converge on the synapse","volume":"28","author":"Fries","year":"2022","journal-title":"Mol. Psychiatr."},{"issue":"5","key":"10.1016\/j.jep.2026.122472_bib11","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/ceo.14343","article-title":"Lipids from ocular meibum and tears may serve as biomarkers for depression and post-traumatic stress disorder","volume":"52","author":"Gary","year":"2023","journal-title":"Clin. Exp. Ophthalmol."},{"issue":"22","key":"10.1016\/j.jep.2026.122472_bib12","doi-asserted-by":"crossref","DOI":"10.3390\/ijms262211118","article-title":"The involvement of ceramide, Sphingosine-1-Phosphate and ganglioside GM1 in regulating some nervous system functions","volume":"26","author":"Giussani","year":"2025","journal-title":"Int. J. Mol. Sci."},{"issue":"17","key":"10.1016\/j.jep.2026.122472_bib13","article-title":"Network pharmacology-guided lipidomics and molecular docking reveals the involvement of sphingolipid metabolism and HIF-1 signaling in Xiaoyao San's blood-nourishing mechanism against depression","volume":"354","author":"Gong","year":"2026","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2026.122472_bib14","first-page":"1","article-title":"The role of sphingolipids in major depressive disorder and associated cognitive impairment: interactions with monoaminergic signaling, neuroinflammation, and neurogenesis","author":"Hoertel","year":"2026","journal-title":"Mol. Psychiatr."},{"issue":"21","key":"10.1016\/j.jep.2026.122472_bib15","doi-asserted-by":"crossref","DOI":"10.3390\/ijms262110699","article-title":"Dry eye disease and psychiatric disorders: neuroimmune mechanisms and therapeutic perspectives","volume":"26","author":"Ka\u0161telan","year":"2025","journal-title":"Int. J. Mol. Sci."},{"issue":"10","key":"10.1016\/j.jep.2026.122472_bib16","first-page":"888","article-title":"An overview of the clinical application of modified danzhi xiaoyao san in the treatment of menstrual disorders","volume":"28","author":"Keke","year":"2012","journal-title":"J. Pract. Med."},{"issue":"7","key":"10.1016\/j.jep.2026.122472_bib17","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1080\/14740338.2024.2385497","article-title":"Eye disorders associated with selective serotonin reuptake inhibitors: a real-world disproportionality analysis of FDA adverse event reporting system","volume":"24","author":"Li","year":"2024","journal-title":"Expert Opin. Drug Saf."},{"issue":"1","key":"10.1016\/j.jep.2026.122472_bib18","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1515\/biol-2022-0491","article-title":"S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model","volume":"17","author":"Lin","year":"2022","journal-title":"Open Life Sci."},{"issue":"15","key":"10.1016\/j.jep.2026.122472_bib19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1167\/iovs.66.15.22","article-title":"Sphingomyelin synthase 2 deletion mitigates oxidative stress-induced NF-\u03baB activation via lipid metabolic reprogramming in dry eye disease","volume":"66","author":"Lu","year":"2025","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.jep.2026.122472_bib20","doi-asserted-by":"crossref","DOI":"10.1039\/D5AY00675A","article-title":"Machine learning-assisted MALDI-MSI to characterize hippocampal subregion lipid and purine metabolic alterations in depression-related dry eye disease","author":"Minsi","year":"2025","journal-title":"Anal. Methods"},{"issue":"6","key":"10.1016\/j.jep.2026.122472_bib21","doi-asserted-by":"crossref","first-page":"846","DOI":"10.3390\/jcm8060846","article-title":"Secretory acid sphingomyelinase in the serum of medicated patients predicts the prospective course of depression","volume":"8","author":"M\u00fchle","year":"2019","journal-title":"J. Clin. Med."},{"issue":"9","key":"10.1016\/j.jep.2026.122472_bib22","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1038\/s41418-018-0245-x","article-title":"Sphingolipid-mediated inflammatory signaling leading to autophagy inhibition converts erythropoiesis to myelopoiesis in human hematopoietic stem\/progenitor cells","volume":"26","author":"Orsini","year":"2019","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.jep.2026.122472_bib23","article-title":"Modified Danzhi Xiaoyao Powder (MDXP) improves the corneal damage in dry eye disease (DED) mice through phagocytosis","volume":"321","author":"Pei","year":"2024","journal-title":"J. Ethnopharmacol."},{"issue":"11","key":"10.1016\/j.jep.2026.122472_bib24","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/j.ophtha.2017.08.029","article-title":"Inflammation in dry eye disease how do we break the cycle?","volume":"124","author":"Rhee","year":"2017","journal-title":"Ophthalmology"},{"key":"10.1016\/j.jep.2026.122472_bib25","article-title":"Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories","volume":"14","author":"Sameer","year":"2023","journal-title":"Front. Psychiatr."},{"key":"10.1016\/j.jep.2026.122472_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155829","article-title":"Saikosaponin antidepressant mechanism: improving the sphingolipid metabolism in the cortex via Apolipoprotein E and triggering neurovascular coupling","volume":"132","author":"Song","year":"2024","journal-title":"Phytomedicine"},{"issue":"8","key":"10.1016\/j.jep.2026.122472_bib27","first-page":"2147","article-title":"New horizon: exercise and a focus on tissue-brain cross talk","volume":"106","author":"Townsend","year":"2021","journal-title":"J. Lipid Res."},{"issue":"5","key":"10.1016\/j.jep.2026.122472_bib28","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.3390\/ijms24054309","article-title":"Lacrimal gland epithelial cells shape immune responses through the modulation of inflammasomes and lipid metabolism","volume":"24","author":"Vanessa","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jep.2026.122472_bib29","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jtos.2022.07.006","article-title":"The role of sphingolipids in meibomian gland dysfunction and ocular surface inflammation","volume":"26","author":"Vikram","year":"2022","journal-title":"Ocul. Surf."},{"issue":"1","key":"10.1016\/j.jep.2026.122472_bib30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.aopr.2024.08.003","article-title":"The alterations of ocular surface metabolism and the related immunity inflammation in dry eye","volume":"5","author":"Wan","year":"2025","journal-title":"Adv. Ophthalmol. Pract. Res."},{"issue":"11","key":"10.1016\/j.jep.2026.122472_bib31","article-title":"Canonical Chinese medicine formula danzhi-xiaoyao-san for treating depression: a systematic review and meta-analysis","volume":"287","author":"Wang","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2026.122472_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2021.114960","article-title":"Canonical Chinese medicine formula danzhi-xiaoyao-san for treating depression: a systematic review and meta-analysis","volume":"287","author":"Wang","year":"2022","journal-title":"J. Ethnopharmacol."},{"issue":"P2","key":"10.1016\/j.jep.2026.122472_bib33","article-title":"The regulatory effect of Angelicae Sinensis Radix on neuroendocrine-immune network and sphingolipid metabolism in CUMS-induced model of depression","volume":"319","author":"Wenxia","year":"2023","journal-title":"J. Ethnopharmacol."},{"issue":"18","key":"10.1016\/j.jep.2026.122472_bib34","article-title":"The antidepressant-like effects of Danzhi Xiaoyao San and its active ingredients","volume":"119","author":"Xie","year":"2023","journal-title":"Phytomedicine"},{"issue":"2","key":"10.1016\/j.jep.2026.122472_bib35","first-page":"222","article-title":"Examples of the clinical application of Modified Xiaoyao San","volume":"27","author":"Xin","year":"2011","journal-title":"J. Changchun Univ. Chin. Med."},{"issue":"9","key":"10.1016\/j.jep.2026.122472_bib36","article-title":"Cap-independent translation of GPLD1 enhances markers of brain health in long-lived mutant and drug-treated mice","volume":"21","author":"Xinna","year":"2022","journal-title":"Aging Cell"},{"issue":"6","key":"10.1016\/j.jep.2026.122472_bib37","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26062722","article-title":"Neuroprotection vs. neurotoxicity: the dual impact of brain lipids in depression","volume":"26","author":"Yan","year":"2025","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.jep.2026.122472_bib38","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.apsb.2024.10.005","article-title":"Discovery of a novel thiophene carboxamide analogue as a highly potent and selective sphingomyelin synthase 2 inhibitor for dry eye disease therapy","volume":"15","author":"Yang","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.jep.2026.122472_bib39","series-title":"Clinical Efficacy Evaluation of Danzhi Xiaoyao San Combined with Direct Current Iontophoresis in the Treatment of Perimenopausal Dry Eye Associated with Heat Stagnation in the Liver Meridian. Master's Thesis","author":"Zhang","year":"2021"},{"issue":"18","key":"10.1016\/j.jep.2026.122472_bib40","doi-asserted-by":"crossref","first-page":"9309","DOI":"10.1080\/07391102.2023.2251067","article-title":"The pharmacological actions of danzhi-xiaoyao-san on depression involve lysophosphatidic acid and microbiota-gut-brain axis: novel insights from a systems pharmacology analysis of a double-blind, randomized, placebo-controlled clinical trial","volume":"42","author":"Zhu","year":"2024","journal-title":"J. Biomol. Struct. Dynam."}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874126013279?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874126013279?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T12:14:28Z","timestamp":1793794468000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874126013279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2027,2]]},"references-count":40,"alternative-id":["S0378874126013279"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2026.122472","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2027,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Modified Danzhi Xiaoyao San ameliorates depression-associated dry eye by modulating sphingolipid metabolism across the liver, hippocampus, and lacrimal gland","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2026.122472","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"122472"}}