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Quercetin has shown anti-allergic effects, but its precise mechanism in AR remains incompletely understood. Quercetin\u2019s impact on interleukin-33 (IL-33)-stimulated rat basophilic leukemia-2H3 (RBL-2H3) cells was assessed using both direct IL-33 exposure and IgE-mediated activation via anti-dinitrophenyl (DNP)-IgE sensitization and DNP- conjugated human serum albumin (HSA) challenge. Cytokine secretion, degranulation, apoptosis, and expression of IL-33 \/suppression of tumorigenicity 2 (ST2)\/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) pathway components were assessed using enzyme-linked immunosorbent assay (ELISA), Western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). A mouse model of AR induced by ovalbumin (OVA) was employed to assess in vivo efficacy. Symptom scores, inflammatory cytokine levels, nasal mucosal histology, and key signaling molecule expression were analyzed to confirm quercetin\u2019s protection. Quercetin significantly suppressed IL-33-induced cytokine production, degranulation, and apoptosis in vitro; these effects were partially reversed by ST2 overexpression. In vivo, quercetin alleviated AR symptoms, reduced serum T helper 2 (Th2) cytokines, OVA-specific IgE (OVA-sIgE), and IL-33 levels, improved histopathology, and downregulated IL-33\/ST2\/NF-\u03baB pathway proteins in nasal tissues. Our findings demonstrate quercetin\u2019s anti-allergic effects against AR, which are likely mediated through suppression of mast cell activation and inhibition of the IL-33\/ST2\/NF-\u03baB signaling cascade.<\/jats:p>","DOI":"10.1038\/s41598-026-57981-6","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T07:05:37Z","timestamp":1781420737000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quercetin modulates mast cell activation and the IL-33\/ST2\/NF-\u03baB axis in allergic rhinitis"],"prefix":"10.1038","volume":"16","author":[{"given":"Yi","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihua","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjie","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"57981_CR1","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1001\/jama.2024.0530","volume":"331","author":"JA Bernstein","year":"2024","unstructured":"Bernstein, J. 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