{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T09:22:12Z","timestamp":1783502532281,"version":"3.55.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100019018","name":"Chinese Academy of Medical Sciences Initiative for Innovative Medicine","doi-asserted-by":"publisher","award":["2022\\u201312M-1-017"],"award-info":[{"award-number":["2022\\u201312M-1-017"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.ejphar.2025.178283","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T15:16:23Z","timestamp":1761146183000},"page":"178283","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Hypericin alleviates depression via the microbiota-gut-brain Axis: Role of Akkermansia muciniphila and glycerophospholipid metabolism"],"prefix":"10.1016","volume":"1008","author":[{"given":"Xiaoya","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangjian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengchen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjie","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuang","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meirong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-1042","authenticated-orcid":false,"given":"Wen","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2025.178283_bib1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1159\/000536063","article-title":"Psychological treatment of comorbid insomnia and depression: a double-blind randomized placebo-controlled trial","volume":"93","author":"Blom","year":"2024","journal-title":"Psychother. Psychosom."},{"key":"10.1016\/j.ejphar.2025.178283_bib2","doi-asserted-by":"crossref","first-page":"10748","DOI":"10.1039\/D2FO01198K","article-title":"The modified outer membrane protein Amuc_1100 of Akkermansia muciniphila improves chronic stress-induced anxiety and depression-like behavior in mice","volume":"13","author":"Cheng","year":"2022","journal-title":"Food Funct."},{"key":"10.1016\/j.ejphar.2025.178283_bib3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrn3346","article-title":"Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour","volume":"13","author":"Cryan","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.ejphar.2025.178283_bib4","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ejphar.2025.178283_bib5","doi-asserted-by":"crossref","first-page":"8411","DOI":"10.1007\/s00253-021-11622-2","article-title":"A next-generation probiotic: akkermansia muciniphila ameliorates chronic stress-induced depressive-like behavior in mice by regulating gut microbiota and metabolites","volume":"105","author":"Ding","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"10.1016\/j.ejphar.2025.178283_bib6","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1001\/archpsyc.65.5.513","article-title":"Population-based study of first onset and chronicity in major depressive disorder","volume":"65","author":"Eaton","year":"2008","journal-title":"Arch. Gen. Psychiatry"},{"key":"10.1016\/j.ejphar.2025.178283_bib7","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s12035-014-8635-7","article-title":"Distribution of secretory phospholipase A2 XIIA in the brain and its role in lipid metabolism and cognition","volume":"50","author":"Ee","year":"2014","journal-title":"Mol. Neurobiol."},{"issue":"Suppl. 7","key":"10.1016\/j.ejphar.2025.178283_bib8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1365-2036.2004.02180.x","article-title":"Review article: serotonin receptors and transporters -- roles in normal and abnormal gastrointestinal motility","volume":"20","author":"Gershon","year":"2004","journal-title":"Aliment. Pharmacol. Ther."},{"key":"10.1016\/j.ejphar.2025.178283_bib9","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1107781","article-title":"Cuscutae semen alleviates CUS-induced depression-like behaviors in mice via the gut microbiota-neuroinflammation axis","volume":"14","author":"Hou","year":"2023","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.178283_bib10","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/10408398.2018.1529653","article-title":"Lipids as biomarkers of brain disorders","volume":"60","author":"Hussain","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"10.1016\/j.ejphar.2025.178283_bib11","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1007\/s11064-022-03596-y","article-title":"Alteration of glycerophospholipid metabolism in Hippocampus of post-stroke depression rats","volume":"47","author":"Jiang","year":"2022","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.ejphar.2025.178283_bib12","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.2174\/1389557520666200727154453","article-title":"Hypericin ameliorates maternal separation-induced cognitive deficits and hippocampal inflammation in rats","volume":"21","author":"Jolodar","year":"2021","journal-title":"Mini Rev. Med. Chem."},{"key":"10.1016\/j.ejphar.2025.178283_bib13","doi-asserted-by":"crossref","first-page":"3859","DOI":"10.3390\/molecules28093859","article-title":"Hypericin ameliorates depression-like behaviors via Neurotrophin signaling pathway mediating m6A epitranscriptome modification","volume":"28","author":"Lei","year":"2023","journal-title":"Molecules"},{"key":"10.1016\/j.ejphar.2025.178283_bib14","doi-asserted-by":"crossref","first-page":"4123","DOI":"10.1038\/s41380-022-01569-9","article-title":"Multi-omics analyses of serum metabolome, gut microbiome and brain function reveal dysregulated microbiota-gut-brain axis in bipolar depression","volume":"27","author":"Li","year":"2022","journal-title":"Mol. Psychiatr."},{"key":"10.1016\/j.ejphar.2025.178283_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.jare.2025.01.042","article-title":"Hypericin photoactivation induces triple-negative breast cancer cells pyroptosis by targeting the ROS\/CALR\/Caspase-3\/GSDME pathway","author":"Liang","year":"2025","journal-title":"J. Adv. Res."},{"key":"10.1016\/j.ejphar.2025.178283_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.116468","article-title":"Banxia Xiexin decoction alleviates AS co-depression disease by regulating the gut microbiome-lipid metabolic axis","volume":"313","author":"Liao","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.ejphar.2025.178283_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2023.104527","article-title":"Gut microbiota and its metabolites in depression: from pathogenesis to treatment","volume":"90","author":"Liu","year":"2023","journal-title":"EBioMedicine"},{"key":"10.1016\/j.ejphar.2025.178283_bib18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13024-024-00720-0","article-title":"Gut microbiota-host lipid crosstalk in Alzheimer's disease: implications for disease progression and therapeutics","volume":"19","author":"Luo","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.ejphar.2025.178283_bib19","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.jad.2016.12.048","article-title":"Clinical use of Hypericum perforatum (St John's wort) in depression: a meta-analysis","volume":"210","author":"Ng","year":"2017","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.ejphar.2025.178283_bib20","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S2215-0366(19)30044-6","article-title":"Mediation of the influence of childhood maltreatment on depression relapse by cortical structure: a 2-year longitudinal observational study","volume":"6","author":"Opel","year":"2019","journal-title":"Lancet Psychiatry"},{"key":"10.1016\/j.ejphar.2025.178283_bib21","doi-asserted-by":"crossref","first-page":"5639","DOI":"10.1002\/ptr.8011","article-title":"Hypericin as a promising natural bioactive naphthodianthrone: a review of its pharmacology, pharmacokinetics, toxicity, and safety","volume":"37","author":"Peng","year":"2023","journal-title":"Phytother Res."},{"key":"10.1016\/j.ejphar.2025.178283_bib22","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1176\/appi.ajp.2015.14070896","article-title":"Gene-environment interaction in youth depression: replication of the 5-HTTLPR moderation in a diverse setting","volume":"172","author":"Rocha","year":"2015","journal-title":"Am. J. Psychiatr."},{"key":"10.1016\/j.ejphar.2025.178283_bib23","doi-asserted-by":"crossref","first-page":"329","DOI":"10.5694\/mja2.50522","article-title":"Antidepressant-induced sexual dysfunction","volume":"212","author":"Rothmore","year":"2020","journal-title":"Med. J. Aust."},{"key":"10.1016\/j.ejphar.2025.178283_bib24","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12974-023-02765-2","article-title":"Stellate ganglion block ameliorated central post-stroke pain with comorbid anxiety and depression through inhibiting HIF-1\u03b1\/NLRP3 signaling following thalamic hemorrhagic stroke","volume":"20","author":"Shi","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.ejphar.2025.178283_bib25","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1001\/jama.2024.5756","article-title":"Management of depression in adults: a review","volume":"332","author":"Simon","year":"2024","journal-title":"JAMA"},{"key":"10.1016\/j.ejphar.2025.178283_bib26","article-title":"Cardiovascular adverse reactions during antidepressant treatment: a drug surveillance report of german-speaking countries between 1993 and 2010","volume":"18","author":"Spindelegger","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.ejphar.2025.178283_bib27","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrgastro.2017.51","article-title":"Non-conventional features of peripheral serotonin signalling - the gut and beyond","volume":"14","author":"Spohn","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.ejphar.2025.178283_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2024.102537","article-title":"Serotonin in depression and Alzheimer's disease: focus on SSRI's beneficial effects","volume":"101","author":"Tahiri","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.ejphar.2025.178283_bib29","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1177\/0269881120913150","article-title":"Divergent pathways mediate 5-HT1A receptor agonist effects on close social interaction, grooming and aggressive behaviour in mice: exploring the involvement of the oxytocin and vasopressin systems","volume":"34","author":"Tan","year":"2020","journal-title":"J. Psychopharmacol."},{"key":"10.1016\/j.ejphar.2025.178283_bib30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jare.2021.10.002","article-title":"Multi-omics data reveals the disturbance of glycerophospholipid metabolism caused by disordered gut microbiota in depressed mice","volume":"39","author":"Tian","year":"2022","journal-title":"J. Adv. Res."},{"key":"10.1016\/j.ejphar.2025.178283_bib31","doi-asserted-by":"crossref","first-page":"E129","DOI":"10.1002\/ijc.26492","article-title":"Radiolabeled iodohypericin as tumor necrosis avid tracer: diagnostic and therapeutic potential","volume":"131","author":"Van de Putte","year":"2012","journal-title":"Int. J. Cancer"},{"key":"10.1016\/j.ejphar.2025.178283_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.115545","article-title":"Novel antidepressant mechanism of hypericin: role of connexin 43-based gap junctions","volume":"167","author":"Wang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejphar.2025.178283_bib33","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s41422-019-0216-x","article-title":"Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression","volume":"29","author":"Wang","year":"2019","journal-title":"Cell Res."},{"key":"10.1016\/j.ejphar.2025.178283_bib34","doi-asserted-by":"crossref","DOI":"10.1111\/cns.14455","article-title":"Luteolin alleviates depression-like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats","volume":"30","author":"Wu","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"10.1016\/j.ejphar.2025.178283_bib35","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s42003-023-05759-1","article-title":"Oral D-ribose causes depressive-like behavior by altering glycerophospholipid metabolism via the gut-brain axis","volume":"7","author":"Xu","year":"2024","journal-title":"Commun. Biol."},{"key":"10.1016\/j.ejphar.2025.178283_bib36","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.joim.2022.05.002","article-title":"Can acupuncture enhance therapeutic effectiveness of antidepressants and reduce adverse drug reactions in patients with depression? A systematic review and meta-analysis","volume":"20","author":"Xu","year":"2022","journal-title":"J. Integr. Med."},{"key":"10.1016\/j.ejphar.2025.178283_bib37","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2023.50897","article-title":"Perinatal depression and risk of suicidal behavior","volume":"7","author":"Yu","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"10.1016\/j.ejphar.2025.178283_bib38","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fncel.2019.00030","article-title":"Resveratrol improves brain-gut axis by regulation of 5-HT-Dependent signaling in the rat model of irritable bowel syndrome","volume":"13","author":"Yu","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.ejphar.2025.178283_bib39","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jep.2015.04.053","article-title":"LC-MS\/MS based studies on the anti-depressant effect of hypericin in the chronic unpredictable mild stress rat model","volume":"169","author":"Zhai","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.ejphar.2025.178283_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2022.108560","article-title":"The protective effect of hypericin on postpartum depression rat model by inhibiting the NLRP3 inflammasome activation and regulating glucocorticoid metabolism","volume":"105","author":"Zhai","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejphar.2025.178283_bib41","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1038\/s41380-020-0744-2","article-title":"The gut microbiome modulates gut-brain axis glycerophospholipid metabolism in a region-specific manner in a nonhuman primate model of depression","volume":"26","author":"Zheng","year":"2021","journal-title":"Mol. Psychiatr."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925010374?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925010374?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:25:44Z","timestamp":1773329144000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299925010374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":41,"alternative-id":["S0014299925010374"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178283","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hypericin alleviates depression via the microbiota-gut-brain Axis: Role of Akkermansia muciniphila and glycerophospholipid metabolism","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178283","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"178283"}}