{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:46:14Z","timestamp":1789577174150,"version":"build-2803163510"},"reference-count":50,"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\/501100010950","name":"Department of Science and Technology of Henan Province","doi-asserted-by":"publisher","award":["252102310506"],"award-info":[{"award-number":["252102310506"]}],"id":[{"id":"10.13039\/501100010950","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.2025.178380","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:08:16Z","timestamp":1763640496000},"page":"178380","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Oxymatrine regulates microglia to produce IFN-\u03b2 by activating the STING\/TBK1\/IRF3 pathway against experimental autoimmune encephalomyelitis"],"prefix":"10.1016","volume":"1009","author":[{"given":"Shuang-shuang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-di","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-meng","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong-yin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-yu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-liang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-juan","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2025.178380_bib1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.it.2013.10.010","article-title":"STING-dependent cytosolic DNA sensing pathways","volume":"35","author":"Barber","year":"2014","journal-title":"Trends Immunol."},{"key":"10.1016\/j.ejphar.2025.178380_bib2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.33594\/000000197","article-title":"Interferon in the CNS","volume":"27","author":"Bhat","year":"2019","journal-title":"Neurosignals"},{"key":"10.1016\/j.ejphar.2025.178380_bib3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.molcel.2014.03.040","article-title":"The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling","volume":"54","author":"Cai","year":"2014","journal-title":"Mol Cell"},{"key":"10.1016\/j.ejphar.2025.178380_bib4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s12264-013-1324-0","article-title":"Polarization of macrophages and microglia in inflammatory demyelination","volume":"29","author":"Cao","year":"2013","journal-title":"Neurosci. Bull."},{"key":"10.1016\/j.ejphar.2025.178380_bib5","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1038\/s41423-020-0405-z","article-title":"A serine protease inhibitor suppresses autoimmune neuroinflammation by activating the STING\/IFN-\u03b2 axis in macrophages","volume":"17","author":"Casella","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.ejphar.2025.178380_bib6","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.2147\/DDDT.S501773","article-title":"Regulation and function of the cGAS-STING pathway: mechanisms, post-translational modifications, and therapeutic potential in immunotherapy","volume":"19","author":"Chen","year":"2025","journal-title":"Drug Des Devel Ther"},{"key":"10.1016\/j.ejphar.2025.178380_bib7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0138592","article-title":"An Oriental medicine, Hyungbangpaedok-San Attenuates motor paralysis in an experimental model of multiple sclerosis by regulating the T cell response","volume":"10","author":"Choi","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.ejphar.2025.178380_bib8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2018.02.015","article-title":"The roles of macrophages and microglia in multiple sclerosis and experimental autoimmune encephalomyelitis","volume":"318","author":"Chu","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"10.1016\/j.ejphar.2025.178380_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.jneuroim.2021.577480","article-title":"Modulation of the HMGB1\/TLR4\/NF-\u03baB signaling pathway in the CNS by matrine in experimental autoimmune encephalomyelitis","volume":"352","author":"Chu","year":"2021","journal-title":"J. Neuroimmunol."},{"key":"10.1016\/j.ejphar.2025.178380_bib10","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.569530","article-title":"Matrine inhibits CNS autoimmunity through an IFN-\u03b2-Dependent mechanism","volume":"11","author":"Chu","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejphar.2025.178380_bib11","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.celrep.2015.04.031","article-title":"Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity","volume":"11","author":"Corrales","year":"2015","journal-title":"Cell Rep."},{"key":"10.1016\/j.ejphar.2025.178380_bib12","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1038\/nn1472","article-title":"ATP mediates rapid microglial response to local brain injury in vivo","volume":"8","author":"Davalos","year":"2005","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.ejphar.2025.178380_bib13","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.celrep.2019.03.098","article-title":"Modular Architecture of the STING C-Terminal tail allows interferon and NF-\u03baB signaling adaptation","volume":"27","author":"de Oliveira Mann","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.ejphar.2025.178380_bib14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41572-018-0041-4","article-title":"Multiple sclerosis","volume":"4","author":"Filippi","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.ejphar.2025.178380_bib15","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1016\/j.neuron.2024.05.025","article-title":"Neurodegeneration and demyelination in multiple sclerosis","volume":"112","author":"Garton","year":"2024","journal-title":"Neuron"},{"key":"10.1016\/j.ejphar.2025.178380_bib16","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1007\/s11064-016-2040-8","article-title":"Neuroprotective effect of matrine in mouse model of vincristine-induced neuropathic pain","volume":"41","author":"Gong","year":"2016","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.ejphar.2025.178380_bib17","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.16495.1","article-title":"Emerging small-molecule treatments for multiple sclerosis: focus on B cells","volume":"8","author":"Gregson","year":"2019","journal-title":"F1000Res"},{"key":"10.1016\/j.ejphar.2025.178380_bib18","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25052589","article-title":"The role of selected interleukins in the development and progression of multiple Sclerosis-A systematic review","volume":"25","author":"Grunwald","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2025.178380_bib19","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nature07317","article-title":"STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling","volume":"455","author":"Ishikawa","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2025.178380_bib20","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0140-6736(23)01473-3","article-title":"Multiple sclerosis","volume":"403","author":"Jakimovski","year":"2024","journal-title":"Lancet"},{"key":"10.1016\/j.ejphar.2025.178380_bib21","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23094788","article-title":"Exploring the pro-phagocytic and anti-inflammatory functions of PACAP and VIP in Microglia: implications for multiple sclerosis","volume":"23","author":"Jansen","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2025.178380_bib22","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.4049\/jimmunol.2001317","article-title":"STING agonist mitigates experimental autoimmune encephalomyelitis by stimulating type I IFN-Dependent and -Independent immune-regulatory pathways","volume":"206","author":"Johnson","year":"2021","journal-title":"J. Immunol."},{"key":"10.1016\/j.ejphar.2025.178380_bib23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.cytogfr.2016.03.013","article-title":"IFN-\u03b2 differentially regulates the function of T cell subsets in MS and EAE","volume":"30","author":"Kavrochorianou","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"10.1016\/j.ejphar.2025.178380_bib24","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.drudis.2006.06.008","article-title":"The impact of interferon-beta treatment on the blood-brain barrier","volume":"11","author":"Kraus","year":"2006","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ejphar.2025.178380_bib25","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/0166-2236(96)10049-7","article-title":"Microglia: a sensor for pathological events in the CNS","volume":"19","author":"Kreutzberg","year":"1996","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.ejphar.2025.178380_bib26","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrneurol.2012.168","article-title":"Progressive multiple sclerosis: pathology and pathogenesis","volume":"8","author":"Lassmann","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.ejphar.2025.178380_bib27","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.immuni.2019.03.025","article-title":"Shared and distinct functions of type I and type III interferons","volume":"50","author":"Lazear","year":"2019","journal-title":"Immunity"},{"key":"10.1016\/j.ejphar.2025.178380_bib28","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1007\/s12035-015-9131-4","article-title":"Korean red ginseng and Ginsenoside-Rb1\/-Rg1 alleviate Experimental Autoimmune encephalomyelitis by suppressing Th1 and Th17 cells and upregulating regulatory T cells","volume":"53","author":"Lee","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.ejphar.2025.178380_bib29","doi-asserted-by":"crossref","first-page":"5571","DOI":"10.4049\/jimmunol.1303258","article-title":"Activation of the STING adaptor attenuates experimental autoimmune encephalitis","volume":"192","author":"Lemos","year":"2014","journal-title":"J. Immunol."},{"key":"10.1016\/j.ejphar.2025.178380_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.jneuroim.2022.577876","article-title":"Matrine inhibits the Wnt3a\/\u03b2-catenin\/TCF7L2 signaling pathway in experimental autoimmune encephalomyelitis","volume":"367","author":"Ma","year":"2022","journal-title":"J. Neuroimmunol."},{"key":"10.1016\/j.ejphar.2025.178380_bib31","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.neuron.2017.11.032","article-title":"Activation of the STING-Dependent type I interferon response reduces microglial reactivity and neuroinflammation","volume":"96","author":"Mathur","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.ejphar.2025.178380_bib32","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/jama.2020.26858","article-title":"Diagnosis and treatment of multiple sclerosis: a review","volume":"325","author":"McGinley","year":"2021","journal-title":"JAMA"},{"key":"10.1016\/j.ejphar.2025.178380_bib33","first-page":"254","article-title":"Effect of oxymatrine on inflammatory responsein rats with myocardial ischemia-reperfusion","volume":"22","author":"Miao","year":"2024","journal-title":"Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease"},{"key":"10.1016\/j.ejphar.2025.178380_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.113476","article-title":"The emerging role of microglia in the development and therapy of multiple sclerosis","volume":"143","author":"Nan","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejphar.2025.178380_bib35","article-title":"Microglial phenotypes and functions in multiple sclerosis","volume":"8","author":"O'Loughlin","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.ejphar.2025.178380_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2023.155065","article-title":"Ginsenoside-Re inhibits experimental autoimmune encephalomyelitis as a mouse model of multiple sclerosis by downregulating TLR4\/MyD88\/NF-\u03baB signaling pathways","volume":"122","author":"Oh","year":"2024","journal-title":"Phytomedicine"},{"key":"10.1016\/j.ejphar.2025.178380_bib37","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri1604","article-title":"Mechanisms of type-I- and type-II-interferon-mediated signalling","volume":"5","author":"Platanias","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ejphar.2025.178380_bib38","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2022.1026449","article-title":"The role of type I IFN in autoimmune and autoinflammatory diseases with CNS involvement","volume":"13","author":"Raftopoulou","year":"2022","journal-title":"Front. Neurol."},{"key":"10.1016\/j.ejphar.2025.178380_bib39","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cytogfr.2014.05.003","article-title":"MITA\/STING: a central and multifaceted mediator in innate immune response","volume":"25","author":"Ran","year":"2014","journal-title":"Cytokine Growth Factor Rev."},{"key":"10.1016\/j.ejphar.2025.178380_bib40","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/948976","article-title":"The benefits and detriments of macrophages\/microglia in models of multiple sclerosis","volume":"2013","author":"Rawji","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"10.1016\/j.ejphar.2025.178380_bib41","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple sclerosis","volume":"378","author":"Reich","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejphar.2025.178380_bib42","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000000729","article-title":"Dimethyl fumarate suppresses granulocyte macrophage colony-stimulating factor-producing Th1 cells in CNS neuroinflammation","volume":"7","author":"Safavi","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"10.1016\/j.ejphar.2025.178380_bib43","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.molmed.2018.11.005","article-title":"Microglia in central nervous System inflammation and multiple sclerosis pathology","volume":"25","author":"Voet","year":"2019","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.ejphar.2025.178380_bib44","article-title":"The STING inhibitor C-176 attenuates MPTP-induced neuroinflammation and neurodegeneration in mouse parkinsonian models","volume":"124","author":"Wang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejphar.2025.178380_bib45","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.21037\/atm-20-5881","article-title":"Oxymatrine attenuates arsenic-induced endoplasmic reticulum stress and calcium dyshomeostasis in hepatic stellate cells","volume":"8","author":"Wang","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"10.1016\/j.ejphar.2025.178380_bib46","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1002\/glia.23634","article-title":"Microglia responses to interleukin-6 and type I interferons in neuroinflammatory disease","volume":"67","author":"West","year":"2019","journal-title":"Glia"},{"key":"10.1016\/j.ejphar.2025.178380_bib47","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1016\/j.cell.2024.05.031","article-title":"STING orchestrates the neuronal inflammatory stress response in multiple sclerosis","volume":"187","author":"Woo","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.ejphar.2025.178380_bib48","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2100225118","article-title":"TBK1 recruitment to STING activates both IRF3 and NF-\u03baB that mediate immune defense against tumors and viral infections","volume":"118","author":"Yum","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejphar.2025.178380_bib49","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/s41586-019-1000-2","article-title":"Structural basis of STING binding with and phosphorylation by TBK1","volume":"567","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2025.178380_bib50","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/s41586-019-1228-x","article-title":"A conserved PLPLRT\/SD motif of STING mediates the recruitment and activation of TBK1","volume":"569","author":"Zhao","year":"2019","journal-title":"Nature"}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925011343?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925011343?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:54:07Z","timestamp":1773831247000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299925011343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":50,"alternative-id":["S0014299925011343"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178380","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":"Oxymatrine regulates microglia to produce IFN-\u03b2 by activating the STING\/TBK1\/IRF3 pathway against experimental autoimmune encephalomyelitis","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178380","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":"178380"}}