Two Japanese pepper (Zanthoxylum piperitum) fruit-derived compounds attenuate IgE-mediated allergic response in vitro and in vivo via inhibition of mast cell degranulation
Two Japanese pepper (Zanthoxylum piperitum) fruit-derived compounds attenuate IgE-mediated allergic response in vitro and in vivo via inhibition of mast cell degranulation
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DOI：
10.1016/j.ejphar.2020.173435
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发表时间：
2020-10-15
影响因子：
5
通讯作者：
Ueno, Masami
中科院分区：
文献类型：
--
作者：
Kono, Ryohei;Nomura, Sachiko;Ueno, Masami
花椒（Zanthoxylum piperitum，ZP）是日本等亚洲国家使用的一种传统药物和胡椒。羟基-α-山椒醇是ZP中含有的一种辛辣物质，据报道可轻微抑制免疫球蛋白E（IgE）介导的肥大细胞脱粒。本研究旨在从ZP中发现新的抗过敏化合物。我们研究IgE介导的肥大细胞脱粒背后的抑制机制。通过抑制作用导向的分离，我们从ZP果实中鉴定出具有脱颗粒抑制作用的化合物：1-乙酰氧基-7-羟基-3，7-二甲基辛-2E，5E-二烯（ZP 1）和8-羟基香叶醇乙酸酯（ZP 2）。ZP 1和ZP 2抑制RBL-2 H3肥大细胞中IgE介导的脱颗粒和A23187介导的脱颗粒。我们的研究结果表明ZP 1和ZP 2通过抑制林恩磷酸化抑制脱粒，然后抑制细胞内Ca 2+动员，蛋白激酶C α磷酸化，膜皱褶和颗粒与质膜融合。口服ZP 1或ZP 2可减弱小鼠IgE介导的被动皮肤过敏反应。组织学观察表明，这种作用是通过抑制肥大细胞脱颗粒而发生的。这些发现表明，ZP 1和ZP 2通过抑制IgE介导的肥大细胞脱颗粒来减轻过敏反应。
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 Ca2+ 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.