{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:53:34Z","timestamp":1790790814587,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T00:00:00Z","timestamp":1559692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2014R1A5A2010008"],"award-info":[{"award-number":["2014R1A5A2010008"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1D1A1B03028366"],"award-info":[{"award-number":["NRF-2017R1D1A1B03028366"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Hispidulin (4\u2032,5,7-trihydroxy-6-methoxyflavone) is a natural compound derived from traditional Chinese medicinal herbs, and it is known to have an anti-inflammatory effect. Here, we investigated the effect of hispidulin on the immunoglobulin E (IgE)-mediated allergic responses in rat basophilic leukemia (RBL)-2H3 mast cells. When RBL-2H3 cells were sensitized with anti-dinitrophenyl (anti-DNP) IgE and subsequently stimulated with DNP-human serum albumin (HSA), histamine and \u03b2-hexosaminidase were released from the cells by degranulation of activated mast cells. However, pretreatment with hispidulin before the stimulation of DNP-HSA markedly attenuated release of both in anti-DNP IgE-sensitized cells. Furthermore, we investigated whether hispidulin inhibits anti-DNP IgE and DNP-HSA-induced passive cutaneous anaphylaxis (PCA), as an animal model for Type I allergies. Hispidulin markedly decreased the PCA reaction and allergic edema of ears in mice. In addition, activated RBL-2H3 cells induced the expression of inflammatory cytokines (tumor necrosis factor-\u03b1 and interleukin-4), which are critical for the pathogenesis of allergic disease, through the activation of c-Jun N-terminal kinase (JNK). Inhibition of JNK activation by hispidulin treatment reduced the induction of cytokine expression in the activated mast cells. Our results indicate that hispidulin might be a possible therapeutic candidate for allergic inflammatory diseases through the suppression of degranulation and inflammatory cytokines expression.<\/jats:p>","DOI":"10.3390\/molecules24112131","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T03:38:01Z","timestamp":1559792281000},"page":"2131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Hispidulin Inhibits Mast Cell-Mediated Allergic Inflammation through Down-Regulation of Histamine Release and Inflammatory Cytokines"],"prefix":"10.3390","volume":"24","author":[{"given":"Dong Eun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, School of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung-jin","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-4507","authenticated-orcid":false,"given":"Min-Jong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1204-2059","authenticated-orcid":false,"given":"Taeg Kyu","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/nri2782","article-title":"Mast cell-orchestrated immunity to pathogens","volume":"10","author":"Abraham","year":"2010","journal-title":"Nat. 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