{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:33:16Z","timestamp":1773660796786,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071806"],"award-info":[{"award-number":["82071806"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515011140"],"award-info":[{"award-number":["2021A1515011140"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016804","name":"Natural Science Foundation of Shenzhen City","doi-asserted-by":"publisher","award":["JCYJ20210324095004012 and JCYJ20190808155603545"],"award-info":[{"award-number":["JCYJ20210324095004012 and JCYJ20190808155603545"]}],"id":[{"id":"10.13039\/100016804","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016804","name":"Natural Science Foundation of Shenzhen City","doi-asserted-by":"publisher","award":["JCYJ20210324095004012 and JCYJ20190808155603545"],"award-info":[{"award-number":["JCYJ20210324095004012 and JCYJ20190808155603545"]}],"id":[{"id":"10.13039\/100016804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Mast cells (MCs) are an important treatment target for high-affinity IgE Fc receptor (Fc\u03b5RI)-mediated allergic diseases. The plant-derived molecule 4-methylumbelliferone (4-MU) has beneficial effects in animal models of inflammation and autoimmunity diseases. The aim of this study was to examine 4-MU effects on MC activation and probe the underlying molecular mechanism(s). We sensitized rat basophilic leukemia cells (RBLs) and mouse bone marrow-derived mast cells (BMMCs) with anti-dinitrophenol (DNP) immunoglobulin (Ig)E antibodies, stimulated them with exposure to DNP-human serum albumin (HSA), and then treated stimulated cells with 4-MU. Signaling-protein expression was determined by immunoblotting. In vivo allergic responses were examined in IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) mouse models. 4-MU inhibited \u03b2-hexosaminidase activity and histamine release dose-dependently in Fc\u03b5RI-activated RBLs and BMMCs. Additionally, 4-MU reduced cytomorphological elongation and F-actin reorganization while down-regulating IgE\/Ag-induced phosphorylation of SYK, NF-\u03baB p65, ERK1\/2, p38, and JNK. Moreover, 4-MU attenuated the PCA allergic reaction (i.e., less ear thickening and dye extravasation). Similarly, we found that 4-MU decreased body temperature, serum histamine, and IL4 secretion in OVA-challenged ASA model mice. In conclusion, 4-MU had a suppressing effect on MC activation both in vitro and in vivo and thus may represent a new strategy for treating IgE-mediated allergic conditions.<\/jats:p>","DOI":"10.3390\/molecules27051577","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T20:48:33Z","timestamp":1645994913000},"page":"1577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Plant-Derived Molecule 4-Methylumbelliferone Suppresses Fc\u03b5RI-Mediated Mast Cell Activation and Allergic Inflammation"],"prefix":"10.3390","volume":"27","author":[{"given":"Hui-Na","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiu-An","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao-Hui","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie-Ning","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Jie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Meng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang-Ning","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen-Fu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5754-8697","authenticated-orcid":false,"given":"Kunmei","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1372-8450","authenticated-orcid":false,"given":"Jia-Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.7150\/thno.34001","article-title":"Regulating Bcl2L12 expression in mast cells inhibits food allergy","volume":"9","author":"Zheng","year":"2019","journal-title":"Theranostics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/all.13702","article-title":"The orphan nuclear receptor NR4A1 promotes FcepsilonRI-stimulated mast cell activation and anaphylaxis by counteracting the inhibitory LKB1\/AMPK axis","volume":"74","author":"Jin","year":"2019","journal-title":"Allergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.bcp.2019.02.015","article-title":"Inhibition of mast cell degranulation by melanin","volume":"163","author":"Kawamoto","year":"2019","journal-title":"Biochem. 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