PMID- 32745602 OWN - NLM STAT- MEDLINE DCOM- 20210518 LR - 20210518 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 885 DP - 2020 Oct 15 TI - Two Japanese pepper (Zanthoxylum piperitum) fruit-derived compounds attenuate IgE-mediated allergic response in vitro and in vivo via inhibition of mast cell degranulation. PG - 173435 LID - S0014-2999(20)30527-6 [pii] LID - 10.1016/j.ejphar.2020.173435 [doi] AB - Zanthoxylum piperitum (ZP, 'Japanese pepper') is a traditional medicine and pepper used in Asian countries such as Japan. Hydroxy-alpha-sanshool, a pungent-tasting substance contained within ZP, has been reported to slightly suppress immunoglobulin E (IgE)-mediated mast cell degranulation. The current study aims to newly identify anti-allergic compounds derived from ZP. We examine the inhibitory mechanisms behind IgE-mediated mast cell degranulation. By inhibitory effect-guided isolation, we identified degranulation inhibitory compounds derived from ZP fruit: 1-acetoxy-7-hydroxy-3, 7-dimethylocta-2E, 5E-diene (ZP1) and 8-hydroxygeranyl acetate (ZP2). ZP1 and ZP2 inhibited IgE-mediated degranulation and A23187-mediated degranulation in RBL-2H3 mast cells. Our findings suggest the inhibition of degranulation by ZP1 and ZP2 was by inhibition of Lyn phosphorylation, followed by inhibition of intracellular Ca(2+) mobilization, protein kinase C alpha phosphorylation, membrane ruffling, and granule-to-plasma membrane fusion. Oral administration of ZP1 or ZP2 attenuated an IgE-mediated passive cutaneous anaphylactic reaction in mice. Histological observation suggests that this effect occurred via inhibition of mast cell degranulation. These findings indicate that ZP1 and ZP2 attenuate allergic reaction via inhibition of IgE-mediated mast cell degranulation. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Kono, Ryohei AU - Kono R AD - Department of Strategic Surveillance for Functional Food and Comprehensive Traditional Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-0012, Japan. Electronic address: r-kono@wakayama-med.ac.jp. FAU - Nomura, Sachiko AU - Nomura S AD - Department of Strategic Surveillance for Functional Food and Comprehensive Traditional Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-0012, Japan. Electronic address: s-nomura@wakayama-med.ac.jp. FAU - Okuno, Yoshiharu AU - Okuno Y AD - Department of Applied Chemistry and Biochemistry, National Institute of Technology, Wakayama College, 77 Noshima, Nada, Gobo, Wakayama, 644-0023, Japan. Electronic address: okuno@wakayama-nct.ac.jp. FAU - Kagiya, Tomoko AU - Kagiya T AD - Faculty of Health Science, Kansai University of Health Science, 2-11-1 Wakaba, Kumatori-cho, Sennan-gun, Osaka, 590-0482, Japan. Electronic address: kagiya@kansai.ac.jp. FAU - Nakamura, Misa AU - Nakamura M AD - Department of Rehabilitation, Osaka Kawasaki Rehabilitation University, 158 Mizuma, Kaizuka City, Osaka, 597-0104, Japan. Electronic address: nakamuram@kawasakigakuen.ac.jp. FAU - Utsunomiya, Hirotoshi AU - Utsunomiya H AD - Department of Strategic Surveillance for Functional Food and Comprehensive Traditional Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-0012, Japan. Electronic address: utsu@wakayama-med.ac.jp. FAU - Ueno, Masami AU - Ueno M AD - Research Center for Community Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-0012, Japan. Electronic address: mu40@wakayama-med.ac.jp. LA - eng PT - Journal Article DEP - 20200731 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Anti-Allergic Agents) RN - 37341-29-0 (Immunoglobulin E) RN - 37H9VM9WZL (Calcimycin) SB - IM MH - Animals MH - Anti-Allergic Agents/*pharmacology MH - Calcimycin/pharmacology MH - Cell Degranulation/*drug effects MH - Cell Line/drug effects MH - Cell Survival/drug effects MH - Fruit/*chemistry MH - Hypersensitivity/*drug therapy MH - Immunoglobulin E/*drug effects MH - Male MH - Mast Cells/*drug effects MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred ICR MH - Passive Cutaneous Anaphylaxis/drug effects MH - Rats MH - Zanthoxylum/*chemistry OTO - NOTNLM OT - Anti-allergic activity OT - Degranulation OT - Mast cell OT - RBL-2H3 OT - Zanthoxylum piperitum EDAT- 2020/08/04 06:00 MHDA- 2021/05/19 06:00 CRDT- 2020/08/04 06:00 PHST- 2019/08/01 00:00 [received] PHST- 2020/07/27 00:00 [revised] PHST- 2020/07/27 00:00 [accepted] PHST- 2020/08/04 06:00 [pubmed] PHST- 2021/05/19 06:00 [medline] PHST- 2020/08/04 06:00 [entrez] AID - S0014-2999(20)30527-6 [pii] AID - 10.1016/j.ejphar.2020.173435 [doi] PST - ppublish SO - Eur J Pharmacol. 2020 Oct 15;885:173435. doi: 10.1016/j.ejphar.2020.173435. Epub 2020 Jul 31.