PMID- 33754256 OWN - NLM STAT- MEDLINE DCOM- 20211108 LR - 20211108 IS - 1573-904X (Electronic) IS - 0724-8741 (Linking) VI - 38 IP - 4 DP - 2021 Apr TI - Ephedra Herb, Mao, Inhibits Antigen-Induced Mast Cell Degranulation by Induction of the Affinity Receptor for IgE Internalization. PG - 569-581 LID - 10.1007/s11095-021-03020-0 [doi] AB - PURPOSE: Ephedra herb (Mao) exerts potent anti-allergic effects. This study aimed to examine the underlying mechanisms of Mao on allergic inflammation using in vitro cultured mast cells (MCs) and an in vivo model of MC-dependent anaphylaxis. METHODS: Bone marrow-derived MCs (BMMCs) were presensitized with anti-2,4-dinitrophenol (DNP) immunoglobulin E (IgE) and challenged with antigens (Ag; DNP-human serum albumin). Degranulation responses and cell surface high-affinity receptor for IgE (FcepsilonRI) expression were assessed with/without Mao treatment. Passive systemic anaphylaxis (PSA)-treated mice were administered Mao and the pathophysiological responses were evaluated. RESULTS: Mao inhibited Ag-induced BMMC degranulation, but not polyclonal activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, indicating that Mao inhibits IgE-dependent activation of BMMCs. Mao-treated BMMCs exhibited significant reductions in expression of surface IgE and its receptor FcepsilonRI. Analysis of subcellular localization revealed that Mao induces FcepsilonRI internalization in BMMCs without degranulation. In the PSA mouse model, Mao administration prevented antigen-induced hypothermia. Mao administration significantly reduced cell surface expression of IgE-bound FcepsilonRI on peritoneal MCs. CONCLUSIONS: Mao induced FcepsilonRI internalization in MCs, thereby inhibiting Ag-induced IgE-dependent degranulation. The inhibitory effects of Mao on MC degranulation may offer a novel therapeutic approach for allergic diseases. FAU - Nagata, Yuka AU - Nagata Y AD - Laboratory of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi Ishikawa, Kanazawa, 920-1192, Japan. FAU - Ando, Hirokazu AU - Ando H AD - Laboratory of Molecular Pharmacognosy, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. FAU - Sasaki, Yohei AU - Sasaki Y AD - Laboratory of Molecular Pharmacognosy, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. FAU - Suzuki, Ryo AU - Suzuki R AUID- ORCID: 0000-0002-9580-7266 AD - Laboratory of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi Ishikawa, Kanazawa, 920-1192, Japan. suzukir@p.kanazawa-u.ac.jp. LA - eng GR - 16H05082/Japan Society for the Promotion of Science/ PT - Journal Article DEP - 20210322 PL - United States TA - Pharm Res JT - Pharmaceutical research JID - 8406521 RN - 0 (Anti-Allergic Agents) RN - 0 (Plant Extracts) RN - 37341-29-0 (Immunoglobulin E) RN - 56092-81-0 (Ionomycin) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Anaphylaxis/*drug therapy/immunology MH - Animals MH - Anti-Allergic Agents/*pharmacology/therapeutic use MH - Cell Degranulation/drug effects/immunology MH - Cells, Cultured MH - Disease Models, Animal MH - Ephedra/*chemistry MH - Female MH - Humans MH - Immunoglobulin E/metabolism MH - Ionomycin/immunology MH - Mast Cells/*drug effects/immunology MH - Medicine, Kampo/methods MH - Mice MH - Plant Extracts/*pharmacology/therapeutic use MH - Plant Stems/chemistry MH - Primary Cell Culture MH - Signal Transduction/drug effects/immunology MH - Tetradecanoylphorbol Acetate/immunology OTO - NOTNLM OT - FcepsilonRI OT - degranulation OT - ephedra herb OT - internalization OT - mast cell EDAT- 2021/03/24 06:00 MHDA- 2021/11/09 06:00 CRDT- 2021/03/23 07:03 PHST- 2020/10/26 00:00 [received] PHST- 2021/02/22 00:00 [accepted] PHST- 2021/03/24 06:00 [pubmed] PHST- 2021/11/09 06:00 [medline] PHST- 2021/03/23 07:03 [entrez] AID - 10.1007/s11095-021-03020-0 [pii] AID - 10.1007/s11095-021-03020-0 [doi] PST - ppublish SO - Pharm Res. 2021 Apr;38(4):569-581. doi: 10.1007/s11095-021-03020-0. Epub 2021 Mar 22.