{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:31:37Z","timestamp":1788996697240,"version":"build-2803163510"},"reference-count":33,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100010881","name":"Suzhou City Science and Technology Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010881","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.jep.2025.120479","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T23:42:41Z","timestamp":1756165361000},"page":"120479","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["Mechanistic insights into the effects of Norisoboldine on intestinal immunity and neuroinflammation in a mouse model of slow transit constipation with depression"],"prefix":"10.1016","volume":"354","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2578-6911","authenticated-orcid":false,"given":"Bensheng","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.jep.2025.120479_bib1","doi-asserted-by":"crossref","DOI":"10.3390\/cells13060485","article-title":"NF-kappaB as an inducible regulator of inflammation in the central nervous system","volume":"13","author":"Anilkumar","year":"2024","journal-title":"Cells"},{"issue":"1","key":"10.1016\/j.jep.2025.120479_bib2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41593-020-00757-6","article-title":"Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis","volume":"24","author":"Berghoff","year":"2021","journal-title":"Nat. Neurosci."},{"issue":"5","key":"10.1016\/j.jep.2025.120479_bib3","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1053\/j.gastro.2019.12.034","article-title":"Mechanisms, evaluation, and management of chronic constipation","volume":"158","author":"Bharucha","year":"2020","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jep.2025.120479_bib4","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2017.95","article-title":"Chronic constipation","volume":"3","author":"Camilleri","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.jep.2025.120479_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2021.111931","article-title":"Phytochemicals as regulators of Th17\/Treg balance in inflammatory bowel diseases","volume":"141","author":"Chang","year":"2021","journal-title":"Biomed. Pharmacother."},{"issue":"1","key":"10.1016\/j.jep.2025.120479_bib6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.alit.2018.11.001","article-title":"Airway innate lymphoid cells in the induction and regulation of allergy","volume":"68","author":"Doherty","year":"2019","journal-title":"Allergol. Int."},{"key":"10.1016\/j.jep.2025.120479_bib7","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1193053","article-title":"Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics","volume":"14","author":"Fang","year":"2023","journal-title":"Front. Immunol."},{"issue":"7","key":"10.1016\/j.jep.2025.120479_bib8","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1002\/j.1532-2149.2013.00439.x","article-title":"Norisoboldine attenuates inflammatory pain via the adenosine A1 receptor","volume":"18","author":"Gao","year":"2014","journal-title":"Eur. J. Pain"},{"issue":"7890","key":"10.1016\/j.jep.2025.120479_bib9","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41586-021-04136-4","article-title":"Antigen-presenting innate lymphoid cells orchestrate neuroinflammation","volume":"600","author":"Grigg","year":"2021","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.jep.2025.120479_bib10","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1136\/gut.35.6.798","article-title":"Discriminant value of psychological distress, symptom profiles, and segmental colonic dysfunction in outpatients with severe idiopathic constipation","volume":"35","author":"Grotz","year":"1994","journal-title":"Gut"},{"issue":"5","key":"10.1016\/j.jep.2025.120479_bib11","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1097\/SLA.0000000000006158","article-title":"Sacral neuromodulation versus conservative treatment for refractory idiopathic slow-transit constipation: the randomized clinical No.2-Trial","volume":"279","author":"Heemskerk","year":"2024","journal-title":"Ann. Surg."},{"issue":"1","key":"10.1016\/j.jep.2025.120479_bib12","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/hep.32449","article-title":"Gut microbiota-derived short-chain fatty acids regulate group 3 innate lymphoid cells in HCC","volume":"77","author":"Hu","year":"2023","journal-title":"Hepatology"},{"issue":"1","key":"10.1016\/j.jep.2025.120479_bib13","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1038\/s41467-020-15612-2","article-title":"Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation","volume":"11","author":"Lehmann","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jep.2025.120479_bib14","article-title":"Engineered 5-HT producing gut probiotic improves gastrointestinal motility and behavior disorder","volume":"12","author":"Li","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"issue":"1","key":"10.1016\/j.jep.2025.120479_bib15","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s41398-024-03127-z","article-title":"Quantitative proteomics combined independent PRM analysis reveals the mitochondrial and synaptic mechanism underlying norisoboldine's antidepressant effects","volume":"14","author":"Li","year":"2024","journal-title":"Transl. Psychiatry"},{"issue":"23","key":"10.1016\/j.jep.2025.120479_bib16","doi-asserted-by":"crossref","DOI":"10.3390\/nu14235013","article-title":"Association between depression, anxiety symptoms and gut microbiota in Chinese elderly with functional constipation","volume":"14","author":"Liang","year":"2022","journal-title":"Nutrients"},{"issue":"10","key":"10.1016\/j.jep.2025.120479_bib17","doi-asserted-by":"crossref","first-page":"6869","DOI":"10.1021\/acs.jmedchem.3c00287","article-title":"Discovery of norisoboldine analogue III(11) as a novel and potent aryl hydrocarbon receptor agonist for the treatment of ulcerative colitis","volume":"66","author":"Lin","year":"2023","journal-title":"J. Med. Chem."},{"issue":"2","key":"10.1016\/j.jep.2025.120479_bib18","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.intimp.2015.08.040","article-title":"Norisoboldine ameliorates DSS-Induced ulcerative colitis in mice through induction of regulatory T cells in colons","volume":"29","author":"Lv","year":"2015","journal-title":"Int. Immunopharmacol."},{"issue":"10","key":"10.1016\/j.jep.2025.120479_bib19","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1111\/j.1572-0241.2000.02313.x","article-title":"Psychological morbidity in women with idiopathic constipation","volume":"95","author":"Mason","year":"2000","journal-title":"Am. J. Gastroenterol."},{"issue":"4","key":"10.1016\/j.jep.2025.120479_bib20","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/bph.13139","article-title":"Microglial M1\/M2 polarization and metabolic states","volume":"173","author":"Orihuela","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jep.2025.120479_bib21","article-title":"Isolation and flow cytometric analysis of immune cells from the ischemic mouse brain","volume":"108","author":"Posel","year":"2016","journal-title":"J. Vis. Exp."},{"issue":"6","key":"10.1016\/j.jep.2025.120479_bib22","article-title":"Chronic constipation in adults: contemporary perspectives and clinical challenges. 1: epidemiology, diagnosis, clinical associations, pathophysiology and investigation","volume":"33","author":"Scott","year":"2021","journal-title":"Neuro Gastroenterol. Motil."},{"key":"10.1016\/j.jep.2025.120479_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.115652","article-title":"Mitochondrial dysfunction: a fatal blow in depression","volume":"167","author":"Song","year":"2023","journal-title":"Biomed. Pharmacother."},{"issue":"4","key":"10.1016\/j.jep.2025.120479_bib24","doi-asserted-by":"crossref","first-page":"170","DOI":"10.21037\/atm-23-6","article-title":"Laxative effect of wenyang yiqi decoction on loperamide-induced astriction model mice","volume":"11","author":"Su","year":"2023","journal-title":"Ann. Transl. Med."},{"issue":"1","key":"10.1016\/j.jep.2025.120479_bib25","doi-asserted-by":"crossref","first-page":"106","DOI":"10.5056\/jnm23147","article-title":"Clinical trial: efficacy of mosapride controlled-release and nortriptyline in patients with functional dyspepsia: a multicenter, double-placebo, double-blinded, randomized controlled, parallel clinical study","volume":"30","author":"Tae","year":"2024","journal-title":"J. Neurogastroenterol Motil."},{"key":"10.1016\/j.jep.2025.120479_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2022.115075","article-title":"Research progress in the treatment of slow transit constipation by traditional Chinese medicine","volume":"290","author":"Wang","year":"2022","journal-title":"J. Ethnopharmacol."},{"issue":"6","key":"10.1016\/j.jep.2025.120479_bib27","first-page":"445","article-title":"[expression and significance of aquaporin 4 in the colonic mucosa of patients with slow transit constipation]","volume":"13","author":"Wang","year":"2010","journal-title":"Zhonghua Wei Chang Wai Ke Za Zhi"},{"issue":"10","key":"10.1016\/j.jep.2025.120479_bib28","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1038\/nprot.2007.315","article-title":"Isolation and subsequent analysis of murine Lamina propria mononuclear cells from colonic tissue","volume":"2","author":"Weigmann","year":"2007","journal-title":"Nat. Protoc."},{"issue":"6","key":"10.1016\/j.jep.2025.120479_bib29","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1007\/s10753-022-01686-1","article-title":"Modulation of microglia M2 polarization and alleviation of hippocampal neuron injury by MiR-106b-5p\/RGMa in a mouse model of status epilepticus","volume":"45","author":"Yu","year":"2022","journal-title":"Inflammation"},{"key":"10.1016\/j.jep.2025.120479_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2023.102371","article-title":"Constipation preceding depression: a population-based cohort study","volume":"67","author":"Yun","year":"2024","journal-title":"eClinicalMedicine"},{"key":"10.1016\/j.jep.2025.120479_bib31","article-title":"Bacteroides fragilis strain ZY-312 facilitates colonic mucosa regeneration in colitis via motivating STAT3 signaling pathway induced by IL-22 from ILC3 secretion","volume":"14","author":"Zhang","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jep.2025.120479_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2023.155203","article-title":"Nobiletin, an active component of wenyang yiqi formula, alleviates constipation associated depression through targeting MAPT to inhibit the MAPK signaling pathway","volume":"126","author":"Zhou","year":"2024","journal-title":"Phytomedicine"},{"key":"10.1016\/j.jep.2025.120479_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.jnutbio.2025.110045","article-title":"Effects and mechanisms of nuciferine on constipation through regulation of the SCF\/c-Kit\/NF-kappaB\/TLR4 signaling pathway in STC model mice","author":"Zikela","year":"2025","journal-title":"J. Nutr. Biochem."}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874125011717?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874125011717?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T18:10:24Z","timestamp":1772820624000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874125011717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":33,"alternative-id":["S0378874125011717"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2025.120479","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mechanistic insights into the effects of Norisoboldine on intestinal immunity and neuroinflammation in a mouse model of slow transit constipation with depression","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2025.120479","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 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":"120479"}}