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Here, in this study, the effect and mechanism of GLA on mast cell degranulation were studied. The results of the anti-DNP IgE-mediated passive cutaneous anaphylaxis (PCA) showed that GLA dramatically inhibited PCA in vivo, as evidenced by reduced Evans blue extravasation and decreased ear thickness. In addition, GLA significantly reduced the release of histamine and \u03b2-hexosaminidase, calcium influx, cytokine (IL-4, TNF-\u03b1, IL-1\u03b2, IL-13, and IL-8) production in the RBL-2H3 (rat basophilic leukemia cells), and RPMCs (peritoneal mast cells) in vitro. Moreover, we further investigated the regulatory mechanism of GLA on antigen-induced mast cells by Western blot, which showed that GLA inhibited Fc\u03b5RI-mediated signal transduction and invalidated the phosphorylation of Syk, Fyn, Lyn, Gab2, and PLC-\u03b31. In addition, GLA inhibited the recombinant mouse high mobility group protein B1- (HMGB1-) induced mast cell degranulation through limiting nuclear translocation of NF-\u03baBp65. Treatment of mast cells with siRNA-HMGB1 significantly inhibited HMGB1 levels, as well as MyD88 and TLR4, decreased intracellular calcium levels, and suppressed the release of \u03b2-hexosaminidase. Meanwhile, GLA increased NrF2 and HO-1 levels by activating p38MAPK phosphorylation. Consequently, these data suggest that GLA regulates the NrF2\/HO-1 signaling pathway through p38MAPK phosphorylation and inhibits HMGB1\/TLR4\/NF-\u03baB signaling pathway to reduce mast cell degranulation and allergic inflammation. Our findings could be used as a promising therapeutic drug against allergic inflammatory disease.<\/jats:p>","DOI":"10.1155\/2021\/6644751","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T16:06:05Z","timestamp":1620057965000},"page":"1-11","source":"Crossref","is-referenced-by-count":12,"title":["Glaucocalyxin A Attenuates Allergic Responses by Inhibiting Mast Cell Degranulation through p38MAPK\/NrF2\/HO-1 and HMGB1\/TLR4\/NF-\u03baB Signaling Pathways"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2481-7317","authenticated-orcid":true,"given":"Yihua","family":"Piao","sequence":"first","affiliation":[{"name":"Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133000, China"},{"name":"Department of Intensive Care Unit, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin, 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