{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T21:58:31Z","timestamp":1769205511499,"version":"3.49.0"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic idiopathic urticaria (CIU) is a condition that significantly impacts patient well-being, requiring effective therapeutic strategies. Formononetin, a natural isoflavone with anti-inflammatory properties, has shown promise in allergic conditions. However, its specific effects and mechanism in CIU are not fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Comparative analyses were conducted between normal and formononetin-treated groups, along with mechanistic investigations into the TAK1\/MAPK pathway both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Cell morphology, cytokine secretion, histamine release, and TAK1\/MAPK pathway alterations were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Formononetin treatment led to a dose-dependent reduction in MC degranulation, histamine release, and secretion of inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6). Additionally, formononetin inhibited the phosphorylation of TAK1, p38, ERK1, and JNK similar to a TAK1 inhibitor in murine and cellular models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Formononetin shows potential as an anti-allergic agent by alleviating inflammatory responses in CIU through suppression of the TAK1\/MAPK pathway in both murine models and MC\/9 cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0340078","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T18:39:32Z","timestamp":1769193572000},"page":"e0340078","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Formononetin ameliorates SP-induced urticaria in mice via suppressing TAK1\/MAK signaling pathway"],"prefix":"10.1371","volume":"21","author":[{"given":"Yan","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4402-8426","authenticated-orcid":true,"given":"Chunyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"issue":"3","key":"pone.0340078.ref001","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.jaci.2004.02.049","article-title":"Chronic urticaria: Pathogenesis and treatment","volume":"114","author":"AP Kaplan","year":"2004","journal-title":"J Allergy Clin Immunol"},{"issue":"2","key":"pone.0340078.ref002","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.1365-2133.2005.06976.x","article-title":"Quality of life in patients with chronic urticaria is differentially impaired and determined by psychiatric comorbidity","volume":"154","author":"P Staubach","year":"2006","journal-title":"Br J Dermatol"},{"key":"pone.0340078.ref003","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.clim.2017.11.004","article-title":"Treatment of chronic spontaneous urticaria: Immunomodulatory approaches","volume":"190","author":"L de Montjoye","year":"2018","journal-title":"Clin Immunol"},{"issue":"6","key":"pone.0340078.ref004","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1067\/mai.2000.111144","article-title":"Diesel exhaust particles directly induce activated mast cells to degranulate and increase histamine levels and symptom severity","volume":"106","author":"D Diaz-Sanchez","year":"2000","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"pone.0340078.ref005","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/j.1365-2222.2009.03256.x","article-title":"Pathogenesis of chronic urticaria","volume":"39","author":"AP Kaplan","year":"2009","journal-title":"Clin Exp Allergy"},{"issue":"3","key":"pone.0340078.ref006","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nri1782","article-title":"Integrated signalling pathways for mast-cell activation","volume":"6","author":"AM Gilfillan","year":"2006","journal-title":"Nat Rev Immunol"},{"issue":"4","key":"pone.0340078.ref007","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1002\/JLB.2A0220-401RRR","article-title":"TAK1 signaling activity links the mast cell cytokine response and degranulation in allergic inflammation","volume":"107","author":"CJF Watson","year":"2020","journal-title":"J Leukoc Biol"},{"issue":"1","key":"pone.0340078.ref008","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bbadis.2010.12.014","article-title":"Mast cells and inflammation","volume":"1822","author":"TC Theoharides","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"pone.0340078.ref009","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bbapap.2005.08.017","article-title":"MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits","volume":"1754","author":"B Kaminska","year":"2005","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"pone.0340078.ref010","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bmcl.2014.11.015","article-title":"Natural therapeutic agents for neurodegenerative diseases from a traditional herbal medicine Pongamia pinnata (L.) 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