PMID- 31195760 OWN - NLM STAT- MEDLINE DCOM- 20191129 LR - 20200225 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 24 IP - 11 DP - 2019 Jun 5 TI - Hispidulin Inhibits Mast Cell-Mediated Allergic Inflammation through Down-Regulation of Histamine Release and Inflammatory Cytokines. LID - 10.3390/molecules24112131 [doi] LID - 2131 AB - Hispidulin (4',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 beta-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-alpha 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. FAU - Kim, Dong Eun AU - Kim DE AD - Department of Otolaryngology, School of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 42601, Korea. entkde@dsmc.or.kr. FAU - Min, Kyoung-Jin AU - Min KJ AD - Department of Immunology, School of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 42601, Korea. kyoungjin.min@gmail.com. FAU - Kim, Min-Jong AU - Kim MJ AUID- ORCID: 0000-0003-1224-4507 AD - Department of Pharmacology, CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea. wowdamien@hanmail.net. FAU - Kim, Sang-Hyun AU - Kim SH AD - Department of Pharmacology, CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea. shkim72@knu.ac.kr. FAU - Kwon, Taeg Kyu AU - Kwon TK AUID- ORCID: 0000-0003-1204-2059 AD - Department of Immunology, School of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 42601, Korea. kwontk@dsmc.or.kr. LA - eng GR - 2014R1A5A2010008/National Research Foundation of Korea/ GR - NRF-2017R1D1A1B03028366/National Research Foundation of Korea/ PT - Journal Article DEP - 20190605 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Cytokines) RN - 0 (Flavones) RN - 0 (Inflammation Mediators) RN - 37341-29-0 (Immunoglobulin E) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - N7F61604C2 (hispidulin) SB - IM MH - Animals MH - Cell Degranulation/drug effects MH - Cytokines/*metabolism MH - *Down-Regulation/drug effects MH - Flavones/chemistry/pharmacology/*therapeutic use MH - *Histamine Release/drug effects MH - Hypersensitivity/complications/*drug therapy MH - Immunoglobulin E/metabolism MH - Inflammation/complications/*drug therapy/pathology MH - Inflammation Mediators/*metabolism MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Male MH - Mast Cells/drug effects/*pathology MH - Mice, Inbred ICR MH - Passive Cutaneous Anaphylaxis/drug effects MH - Phosphorylation/drug effects PMC - PMC6600596 OTO - NOTNLM OT - Hispidulin OT - allergy OT - inflammation OT - mast cells COIS- The authors declare no conflicts of interest. EDAT- 2019/06/15 06:00 MHDA- 2019/11/30 06:00 PMCR- 2019/06/05 CRDT- 2019/06/15 06:00 PHST- 2019/05/10 00:00 [received] PHST- 2019/05/24 00:00 [revised] PHST- 2019/06/04 00:00 [accepted] PHST- 2019/06/15 06:00 [entrez] PHST- 2019/06/15 06:00 [pubmed] PHST- 2019/11/30 06:00 [medline] PHST- 2019/06/05 00:00 [pmc-release] AID - molecules24112131 [pii] AID - molecules-24-02131 [pii] AID - 10.3390/molecules24112131 [doi] PST - epublish SO - Molecules. 2019 Jun 5;24(11):2131. doi: 10.3390/molecules24112131.