Elucidation of the mechanism of Japanese pepper(Zanthoxylum piperitum)-derived degranulation inhibitors

• Project/Area Number: 17K18025
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits; Food science
• Research Institution: Wakayama Medical University
• Principal Investigator: Ryohei Kono 和歌山県立医科大学, 医学部, 助教 (70569110)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アレルギー / 山椒 / 花粉症 / 脱顆粒 / 抗アレルギー作用 / 食品 / 天然物 / 抗アレルギー

Outline of Final Research Achievements

Zanthoxylum piperitum (ZP, ‘Japanese pepper’) is a traditional medicine and pepper used in Asian countries such as Japan. The current study aims to newly identify anti-allergic compounds derived from ZP. By inhibitory effect-guided isolation based on IgE-mediated mast cell degranulation, 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). 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. These findings indicate that ZP1 and ZP2 attenuate allergic reaction via inhibition of IgE-mediated mast cell degranulation.

Academic Significance and Societal Importance of the Research Achievements

本研究では山椒から新たに二つの脱顆粒抑制物質を単離、同定し、その作用機序を明らかにした。アレルギー疾患に対する治療方法は複数あるが、その選択肢を増やすことは有意義である。さらに山椒そのものを食生活に取り入れることで、アレルギー予防・改善が期待される

Research Products

• [Journal Article] Biological and epidemiological evidence of anti-allergic effects of traditional Japanese food ume (Prunus mume) (2018)
  • Author(s): Kono Ryohei、Nakamura Misa、Nomura Sachiko、Kitano Naomi、Kagiya Tomoko、Okuno Yoshiharu、Inada Ken-ichi、Tokuda Akihiko、Utsunomiya Hirotoshi、Ueno Masami
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1-15
  • DOI: 10.1038/s41598-018-30086-5
  • Peer Reviewed / Open Access
• [Presentation] 山椒由来geranyl acetate誘導体はマスト細胞の脱顆粒を抑制する (2019)
  • Author(s): 河野良平、野村幸子、奥野祥治、鍵弥朋子、中村美砂、宇都宮洋才
  • Organizer: 第２6回日本未病システム学会学術総会
• [Presentation] 山椒の抗アレルギー効果について (2017)
  • Author(s): 河野良平、野村幸子、鍵弥朋子、奥野祥治、中村美砂、宇都宮洋才
  • Organizer: 第２４回日本未病システム学会学術総会