PMID- 37331292 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20231023 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 121 DP - 2023 Aug TI - Norisoboldine exerts antiallergic effects on IgE/ovalbumin-induced allergic asthma and attenuates FcepsilonRI-mediated mast cell activation. PG - 110473 LID - S1567-5769(23)00796-8 [pii] LID - 10.1016/j.intimp.2023.110473 [doi] AB - Allergic asthma is an inflammatory lung disorder, and mast cells play crucial roles in the development of this allergic disease. Norisoboldine (NOR), the major isoquinoline alkaloid present in Radix Linderae, has received considerable attention because it has anti-inflammatory effects. Herein, the aim of this study was to explore the antiallergic effects of NOR on allergic asthma in mice and mast cell activation. In a murine model of ovalbumin (OVA)-induced allergic asthma, oral administration at 5 mg/kg body weight (BW) of NOR produced strong reductions in serum OVA-specific immunoglobulin E (IgE) levels, airway hyperresponsiveness, and bronchoalveolar lavage fluid (BALF) eosinophilia, while an increase in CD4(+)Foxp3(+) T cells of the spleen was detected. Histological studies demonstrated that NOR treatment significantly ameliorated the progression of airway inflammation including the recruitment of inflammatory cells and mucus production by decreasing levels of histamine, prostaglandin D(2) (PGD(2)), interleukin (IL)-4, IL-5, IL-6, and IL-13 in BALF. Furthermore, our results revealed that NOR (3 approximately 30 muM) dose-dependently reduced expression of the high-affinity receptor for IgE (FcepsilonRI) and the production of PGD(2) and inflammatory cytokines (IL-4, IL-6, IL-13, and TNF-alpha), and also decreased degranulation of bone marrow-derived mast cells (BMMCs) activated by IgE/OVA. In addition, a similar suppressive effect on BMMC activation was observed by inhibition of the FcepsilonRI-mediated c-Jun N-terminal kinase (JNK) signaling pathway using SP600125, a selective JNK inhibitor. Collectively, these results suggest that NOR may have therapeutic potential for allergic asthma at least in part through regulating the degranulation and the release of mediators by mast cells. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Chang, Jer-Hwa AU - Chang JH AD - School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. FAU - Chuang, Hsiao-Chi AU - Chuang HC AD - School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. FAU - Fan, Chia-Kwung AU - Fan CK AD - Department of Molecular Parasitology and Tropical Diseases, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Hou, Tsung-Yun AU - Hou TY AD - Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. FAU - Chang, Yu-Cheng AU - Chang YC AD - Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Lee, Yueh-Lun AU - Lee YL AD - Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: yllee@tmu.edu.tw. LA - eng PT - Journal Article DEP - 20230616 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 9006-59-1 (Ovalbumin) RN - 0 (norisoboldine) RN - 0 (Anti-Allergic Agents) RN - 0 (Receptors, IgE) RN - 0 (Interleukin-6) RN - 0 (Interleukin-13) RN - 0 (Alkaloids) RN - 0 (Cytokines) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Mice MH - Animals MH - Ovalbumin/metabolism MH - Mast Cells MH - *Anti-Allergic Agents/adverse effects MH - Receptors, IgE/metabolism MH - Interleukin-6/metabolism MH - Interleukin-13/metabolism MH - *Asthma/chemically induced/drug therapy/metabolism MH - Lung/pathology MH - *Alkaloids/therapeutic use MH - Cytokines/metabolism MH - Bronchoalveolar Lavage Fluid MH - Immunoglobulin E MH - Mice, Inbred BALB C MH - Disease Models, Animal OTO - NOTNLM OT - Allergic asthma OT - Immunoglobulin E OT - Mast cell OT - Norisoboldine COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/06/19 00:42 MHDA- 2023/10/23 00:43 CRDT- 2023/06/18 18:11 PHST- 2023/02/23 00:00 [received] PHST- 2023/05/31 00:00 [revised] PHST- 2023/06/07 00:00 [accepted] PHST- 2023/10/23 00:43 [medline] PHST- 2023/06/19 00:42 [pubmed] PHST- 2023/06/18 18:11 [entrez] AID - S1567-5769(23)00796-8 [pii] AID - 10.1016/j.intimp.2023.110473 [doi] PST - ppublish SO - Int Immunopharmacol. 2023 Aug;121:110473. doi: 10.1016/j.intimp.2023.110473. Epub 2023 Jun 16.