{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:12:26Z","timestamp":1787681546688,"version":"build-2784847793"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017686","name":"Fujian Provincial Health Technology Project","doi-asserted-by":"publisher","award":["2019-CX-34"],"award-info":[{"award-number":["2019-CX-34"]}],"id":[{"id":"10.13039\/501100017686","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872879"],"award-info":[{"award-number":["81872879"]}],"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":["81973309"],"award-info":[{"award-number":["81973309"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013795","name":"Fujian Medical University","doi-asserted-by":"publisher","award":["087376"],"award-info":[{"award-number":["087376"]}],"id":[{"id":"10.13039\/501100013795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013795","name":"Fujian Medical University","doi-asserted-by":"publisher","award":["2018Y9073"],"award-info":[{"award-number":["2018Y9073"]}],"id":[{"id":"10.13039\/501100013795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013795","name":"Fujian Medical University","doi-asserted-by":"publisher","award":["2018ZX09711001-003-024"],"award-info":[{"award-number":["2018ZX09711001-003-024"]}],"id":[{"id":"10.13039\/501100013795","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":[[2022,1]]},"DOI":"10.1016\/j.ejphar.2021.174690","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:06:55Z","timestamp":1638922015000},"page":"174690","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"special_numbering":"C","title":["The immunomodulatory effect of koumine on B cells under dependent and independent responses by T cells"],"prefix":"10.1016","volume":"914","author":[{"given":"Yarong","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengting","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2021.174690_bib1","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0211-18.2018","article-title":"The role of interleukin-10 in mediating the effect of immune challenge on mouse Gonadotropin-releasing hormone neurons in vivo","volume":"5","author":"Barab\u00e1s","year":"2018","journal-title":"eNeuro"},{"key":"10.1016\/j.ejphar.2021.174690_bib2","article-title":"B cell targeted therapies in autoimmune disease","volume":"8","author":"Barnas","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"10.1016\/j.ejphar.2021.174690_bib3","first-page":"1399","article-title":"A unique role of the cholera toxin A1-DD adjuvant for long-term plasma and memory B cell development","volume":"186","author":"Bemark","year":"2011","journal-title":"J.I."},{"key":"10.1016\/j.ejphar.2021.174690_bib4","doi-asserted-by":"crossref","first-page":"151899","DOI":"10.1016\/j.imbio.2019.151899","article-title":"Mechanistic basis of co-stimulatory CD40-CD40L ligation mediated regulation of immune responses in cancer and autoimmune disorders","volume":"225","author":"Chand Dakal","year":"2020","journal-title":"Immunobiology"},{"key":"10.1016\/j.ejphar.2021.174690_bib5","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1007\/s00705-015-2419-x","article-title":"Impact on antibody responses of B-cell-restricted transgenic expression of a viral gene inhibiting activation of NF-\u03baB and NFAT","volume":"160","author":"de Paiva e Almeida","year":"2015","journal-title":"Arch. Virol."},{"key":"10.1016\/j.ejphar.2021.174690_bib6","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0008358","article-title":"T. brucei infections abrogate diverse plasma cell-mediated effector B cell responses, independently of their specificity, affinity and host genetic background","volume":"14","author":"De Trez","year":"2020","journal-title":"PLoS Neglected Trop. Dis."},{"key":"10.1016\/j.ejphar.2021.174690_bib7","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.139032","article-title":"Pathogenic, glycolytic PD-1+ B cells accumulate in the hypoxic RA joint","volume":"5","author":"Floudas","year":"2020","journal-title":"JCI Insight"},{"key":"10.1016\/j.ejphar.2021.174690_bib8","series-title":"A Modern Herbal the Medicinal Culinary Cosmetic and Economic Properties Cultivation and Folk-Lore of Herbs, Grases Fungi, Shrubs & Trees with All Their Modern Uses","author":"Grieve","year":"1970"},{"key":"10.1016\/j.ejphar.2021.174690_bib9","doi-asserted-by":"crossref","first-page":"987","DOI":"10.17219\/acem\/74437","article-title":"Relationship between the expression of CD25 and CD69 on the surface of lymphocytes T and B from peripheral blood and bone marrow of patients with chronic lymphocytic leukemia and established prognostic factors of this disease","volume":"27","author":"Grywalska","year":"2018","journal-title":"Adv. Clin. Exp. Med."},{"key":"10.1016\/j.ejphar.2021.174690_bib10","article-title":"CD22 promotes B-1b cell responses to T cell\u2013independent type 2 antigens","author":"Haas","year":"2018","journal-title":"J.I."},{"key":"10.1016\/j.ejphar.2021.174690_bib11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.coi.2019.04.003","article-title":"Antigen presentation by dendritic cells for B cell activation","volume":"58","author":"Heath","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"10.1016\/j.ejphar.2021.174690_bib12","doi-asserted-by":"crossref","first-page":"42781","DOI":"10.1038\/srep42781","article-title":"Expression profiling of TRIM protein family in THP1-derived macrophages following TLR stimulation","volume":"7","author":"Jiang","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2021.174690_bib13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/9347696","article-title":"Koumine attenuates neuroglia activation and inflammatory response to neuropathic pain","author":"Jin","year":"2018","journal-title":"Neural Plast."},{"key":"10.1016\/j.ejphar.2021.174690_bib14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jep.2014.01.003","article-title":"Medicinal plants of the genus Gelsemium (Gelsemiaceae, Gentianales)\u2014a review of their phytochemistry, pharmacology, toxicology and traditional use","volume":"152","author":"Jin","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.ejphar.2021.174690_bib15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s11418-018-1229-3","article-title":"The analgesic effect and possible mechanisms by which koumine alters type II collagen-induced arthritis in rats","volume":"73","author":"Jin","year":"2019","journal-title":"J. Nat. Med."},{"key":"10.1016\/j.ejphar.2021.174690_bib16","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.1365-2249.2009.03979.x","article-title":"Translational Mini-Review Series on B Cell-Directed Therapies: recent advances in B cell-directed biological therapies for autoimmune disorders","volume":"157","author":"Levesque","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"10.1016\/j.ejphar.2021.174690_bib17","volume":"vol. 6","author":"Lisha","year":"1999"},{"key":"10.1016\/j.ejphar.2021.174690_bib18","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s00213-012-2867-x","article-title":"The active alkaloids of Gelsemium elegans Benth. are potent anxiolytics","volume":"225","author":"Liu","year":"2013","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.ejphar.2021.174690_bib19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0213832","article-title":"Isolation of B-cells using Miltenyi MACS bead isolation kits","volume":"14","author":"Moore","year":"2019","journal-title":"PLoS One"},{"key":"10.1016\/j.ejphar.2021.174690_bib20","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1177\/0961203315606982","article-title":"Caspase-1 is required for maintenance of marginal zone B cells in pristane-induced lupus","volume":"25","author":"Morse","year":"2016","journal-title":"Lupus"},{"key":"10.1016\/j.ejphar.2021.174690_bib21","doi-asserted-by":"crossref","first-page":"6979","DOI":"10.1002\/j.1460-2075.1996.tb01090.x","article-title":"The cell death inhibitor Bcl-2 and its homologues influence control of cell cycle entry","volume":"15","author":"O'Reilly","year":"1996","journal-title":"EMBO J."},{"key":"10.1016\/j.ejphar.2021.174690_bib22","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.4110\/in.2018.18.e34","article-title":"Expansion and sub-classification of T cell-dependent antibody responses to encompass the role of innate-like T cells in antibody responses","volume":"18","author":"Park","year":"2018","journal-title":"Immune Netw."},{"key":"10.1016\/j.ejphar.2021.174690_bib23","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1093\/rheumatology\/kex067","article-title":"Obinutuzumab induces superior B-cell cytotoxicity to rituximab in rheumatoid arthritis and systemic lupus erythematosus patient samples","volume":"56","author":"Reddy","year":"2017","journal-title":"Rheumatology"},{"key":"10.1016\/j.ejphar.2021.174690_bib24","first-page":"1921","article-title":"Age-associated B cells express a diverse repertoire of V H and V\u03ba genes with somatic hypermutation","volume":"198","author":"Russell Knode","year":"2017","journal-title":"J.I."},{"key":"10.1016\/j.ejphar.2021.174690_bib25","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/intimm\/dxy077","article-title":"RNA-binding protein Ptbp1 is essential for BCR-mediated antibody production","volume":"31","author":"Sasanuma","year":"2019","journal-title":"Int. Immunol."},{"key":"10.1016\/j.ejphar.2021.174690_bib26","doi-asserted-by":"crossref","DOI":"10.3892\/or.2018.6789","article-title":"Effects of green tea, matcha tea and their components epigallocatechin gallate and quercetin on MCF-7 and MDA-MB-231 breast carcinoma cells","author":"Schrder","year":"2018","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.ejphar.2021.174690_bib27","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0146881","article-title":"Evaluation of selected immunomodulatory glycoproteins as an adjunct to cancer immunotherapy","volume":"11","author":"Sekhon","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.ejphar.2021.174690_bib28","first-page":"2374","article-title":"B cell\u2013intrinsic Ido1 regulates humoral immunity to T cell\u2013independent antigens","volume":"195","author":"Shinde","year":"2015","journal-title":"J.I."},{"key":"10.1016\/j.ejphar.2021.174690_bib29","doi-asserted-by":"crossref","first-page":"17943","DOI":"10.1038\/srep17943","article-title":"A novel, native-format bispecific antibody triggering T-cell killing of B-cells is robustly active in mouse tumor models and cynomolgus monkeys","volume":"5","author":"Smith","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2021.174690_bib30","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.1016\/j.chroma.2011.04.025","article-title":"Preparative separation of alkaloids from Gelsemium elegans Benth. using pH-zone-refining counter-current chromatography","volume":"1218","author":"Su","year":"2011","journal-title":"J. Chromatogr. A"},{"key":"10.1016\/j.ejphar.2021.174690_bib31","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/eji.201646549","article-title":"IL-10 production in murine IgM + CD138 hi cells is driven by Blimp-1 and downregulated in class-switched cells","volume":"47","author":"Suzuki-Yamazaki","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.ejphar.2021.174690_bib32","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/imr.12747","article-title":"T FH cells in bystander and cognate interactions with B cells","volume":"288","author":"Wan","year":"2019","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.ejphar.2021.174690_bib33","doi-asserted-by":"crossref","first-page":"805","DOI":"10.3892\/mmr.2016.6097","article-title":"Inhibition of TLR4 protects rat islets against lipopolysaccharide-induced dysfunction","volume":"15","author":"Wang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.ejphar.2021.174690_bib34","first-page":"562","article-title":"[Effect of koumine on proliferation of murine CD4+ T cells purified by magnetic-activated cell sorting in vitro]","volume":"25","author":"Wang","year":"2005","journal-title":"Di Yi Jun Yi Da Xue Xue Bao"},{"key":"10.1016\/j.ejphar.2021.174690_bib35","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.dci.2019.05.002","article-title":"Blimp-1 is involved in B cell activation and maturation in Nile tilapia (Oreochromis niloticus)","volume":"98","author":"Wu","year":"2019","journal-title":"Dev. Comp. Immunol."},{"key":"10.1016\/j.ejphar.2021.174690_bib36","series-title":"A Study on Anti-inflammatory Effect of Gelsemium Elegans Benth. Pharmacology and Clinics of Chinese Materia Medica","author":"Xu","year":"1991"},{"key":"10.1016\/j.ejphar.2021.174690_bib37","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jdermsci.2018.04.009","article-title":"Anti-pruritic and anti-inflammatory effects of oxymatrine in a mouse model of allergic contact dermatitis","volume":"91","author":"Xu","year":"2018","journal-title":"J. Dermatol. Sci."},{"key":"10.1016\/j.ejphar.2021.174690_bib38","first-page":"71","article-title":"Semaphorin 4C protects against allergic inflammation: requirement of regulatory CD138 + plasma cells","volume":"198","author":"Xue","year":"2017","journal-title":"J.I."},{"key":"10.1016\/j.ejphar.2021.174690_bib39","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1021\/acs.jnatprod.6b00554","article-title":"Effects of koumine on adjuvant- and collagen-induced arthritis in rats","volume":"79","author":"Yang","year":"2016","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ejphar.2021.174690_bib40","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3390\/ijms17030430","article-title":"Koumine attenuates lipopolysaccaride-stimulated inflammation in RAW264.7 macrophages, coincidentally associated with inhibition of NF-\u03baB, ERK and p38 pathways","volume":"17","author":"Yuan","year":"2016","journal-title":"IJMS"},{"key":"10.1016\/j.ejphar.2021.174690_bib41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/8325102","article-title":"Immunoregulatory effect of koumine on nonalcoholic fatty liver disease rats","author":"Yue","year":"2019","journal-title":"J. Immunol. Res."},{"key":"10.1016\/j.ejphar.2021.174690_bib42","article-title":"Paeoniflorin selectively inhibits LPS-provoked B-cell function","volume":"9","author":"Zhang","year":"2015","journal-title":"J. Pharmacol. Sci."},{"key":"10.1016\/j.ejphar.2021.174690_bib43","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.fitote.2014.11.002","article-title":"Gelsemium analgesia and the spinal glycine receptor\/allopregnanolone pathway","volume":"100","author":"Zhang","year":"2015","journal-title":"Fitoterapia"},{"key":"10.1016\/j.ejphar.2021.174690_bib44","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1071\/FP18080","article-title":"The effects of total glucosides of paeony (TGP) and paeoniflorin (Pae) on inflammatory-immune responses in rheumatoid arthritis (RA)","volume":"46","author":"Zhang","year":"2019","journal-title":"Funct. Plant Biol."},{"key":"10.1016\/j.ejphar.2021.174690_bib45","doi-asserted-by":"crossref","first-page":"382","DOI":"10.3389\/fonc.2018.00382","article-title":"Detection of the MYD88 p.L265P mutation in the CSF of a patient with secondary central nervous system lymphoma","volume":"8","author":"Zorofchian","year":"2018","journal-title":"Front. Oncol."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921008463?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921008463?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:16:17Z","timestamp":1762143377000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299921008463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":45,"alternative-id":["S0014299921008463"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174690","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The immunomodulatory effect of koumine on B cells under dependent and independent responses by T cells","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174690","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"174690"}}