Evaluation and elucidation of mechanism of action of the relieving effect of a metabolite of fish oil component on allergic symptoms

• Project/Area Number: 17K07792
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Ehime University
• Principal Investigator: Nishi Kosuke 愛媛大学, 農学研究科, 准教授 (80578097)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 魚油 / DHA / 代謝物 / モデルマウス / サイトカイン / 花粉症 / アレルギー / マスト細胞 / アレルギーモデル / ドコサヘキサエノイルエタノールアミド / リンパ球 / RBL-2H3細胞 / 脱顆粒 / DHEA / 代謝

Outline of Final Research Achievements

Results of epidemiological studies and animal experiments suggest an anti-allergy effect of fish oil; however, its underlying mechanism still remains unclear. To elucidate the mechanism of action of the anti-allergy effect of fish oil, this study was conducted based on docosahexaenoic acid (DHA), an ingredient of fish oil. The result revealed that docosahexaenoyl ethanolamide (DHEA), a metabolite of DHA produced in our body, suppresses antigen-induced mast cell activation. In addition, oral administration of DHEA mitigated an allergic symptom of pollinosis model mice.

Academic Significance and Societal Importance of the Research Achievements

本研究の実施により、魚油のアレルギー症状緩和効果は、主成分の一つであるDHAのはたらきだけでなく、それが私たちの体内で変換されて生じる代謝物の一つであるDHEAのはたらきも重要である可能性が示唆された。また、DHEAの経口投与によって、花粉症モデルマウスのアレルギー症状が緩和されたことから、DHEAを活用した医薬品や保健機能食品の開発などの応用展開の可能性が考えられる。

Research Products

• [Journal Article] Trigonelline: An alkaloid with anti-degranulation properties (2020)
  • Author(s): Nugrahini Arita Dewi、Ishida Momoko、Nakagawa Toshifumi、Nishi Kosuke、Sugahara Takuya
  • Journal Title: Molecular Immunology Volume: 118 Pages: 201-209
  • DOI: 10.1016/j.molimm.2019.12.020
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Docosahexaenoyl ethanolamide mitigates IgE-mediated allergic reactions by inhibiting mast cell degranulation and regulating allergy-related immune cells (2019)
  • Author(s): Nishi Kosuke、Kanayama Yoshiki、Kim In-Hae、Nakata Akihiro、Nishiwaki Hisashi、Sugahara Takuya
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 16213-16213
  • DOI: 10.1038/s41598-019-52317-z
  • Peer Reviewed / Open Access
• [Journal Article] Structure-Activity Relationships of Fish Oil Derivatives with Antiallergic Activity in Vitro and in Vivo (2019)
  • Author(s): Kim In-Hae、Kanayama Yoshiki、Nishiwaki Hisashi、Sugahara Takuya、Nishi Kosuke
  • Journal Title: Journal of Medicinal Chemistry Volume: 62 Issue: 21 Pages: 9576-9592
  • DOI: 10.1021/acs.jmedchem.9b00994
  • Peer Reviewed
• [Journal Article] Anti-degranulation activity of caffeine: In vitro and in vivo study (2019)
  • Author(s): Nugrahini Arita Dewi、Ishida Momoko、Nakagawa Toshifumi、Nishi Kosuke、Sugahara Takuya
  • Journal Title: Journal of Functional Foods Volume: 60 Pages: 103422-103422
  • DOI: 10.1016/j.jff.2019.103422
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Inhibitory effect of aqueous extract of Cuminum cyminum L. seed on degranulation of RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice (2019)
  • Author(s): Hada Makoto、Nishi Kosuke、Ishida Momoko、Onda Hiroyuki、Nishimoto Sogo、Sugahara Takuya
  • Journal Title: Cytotechnology Volume: 71 Issue: 2 Pages: 599-609
  • DOI: 10.1007/s10616-019-00309-2
  • Peer Reviewed
• [Journal Article] Suppressive effect of ethanol extract from mango (Mangifera indica L.) peel on IgE production in vitro and in vivo (2018)
  • Author(s): Ishida Momoko、Sasaki Tomoko、Nishi Kosuke、Tamamoto Takeshi、Sugahara Takuya
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 印刷中 Issue: 4 Pages: 732-739
  • DOI: 10.1080/09168451.2017.1412250
  • Peer Reviewed
• [Journal Article] Inhibitory effect of Japanese black vinegar on IgE-mediated degranulation of RBL-2H3 cells and a murine model of Japanese cedar pollinosis (2018)
  • Author(s): Awane Seiji、Nishi Kosuke、Ishida Momoko、Nagano Masanobu、Hashiguchi Kazunori、Fujii Akira、Sugahara Takuya
  • Journal Title: Cytotechnology Volume: 印刷中 Issue: 3 Pages: 961-974
  • DOI: 10.1007/s10616-018-0208-6
  • Peer Reviewed
• [Journal Article] Anti-inflammatory effect of lysozyme from hen egg white on mouse peritoneal macrophages (2018)
  • Author(s): Tagashira Ayuka、Nishi Kosuke、Matsumoto Shinya、Sugahara Takuya
  • Journal Title: Cytotechnology Volume: 印刷中 Issue: 3 Pages: 929-938
  • DOI: 10.1007/s10616-017-0184-2
  • Peer Reviewed
• [Journal Article] Immunostimulatory effect of dried bonito extract on mouse macrophage cell lines and mouse primary peritoneal macrophages (2017)
  • Author(s): Ishida Momoko、Nishi Kosuke、Shinohara Kozue、Kunihiro Nanami、Osajima Katsuhiro、Suemitsu Tomokazu、Sugahara Takuya
  • Journal Title: Cytotechnology Volume: 69 Issue: 2 Pages: 229-244
  • DOI: 10.1007/s10616-016-0053-4
  • Peer Reviewed
• [Journal Article] Suppressive effect of ethanol extract from passion fruit seeds on IgE production (2017)
  • Author(s): Mizusaki Ai、Nishi Kosuke、Nishiwaki Hisashi、Ishida Momoko、Tamamoto Takeshi、Sugahara Takuya
  • Journal Title: Journal of Functional Foods Volume: 32 Pages: 176-184
  • DOI: 10.1016/j.jff.2017.02.030
  • Peer Reviewed
• [Journal Article] Immunomodulatory Activity of Octenyl Succinic Anhydride Modified Porang (Amorphophallus oncophyllus) Glucomannan on Mouse Macrophage-Like J774.1 Cells and Mouse Primary Peritoneal Macrophages (2017)
  • Author(s): Gurusmatika Sellen、Nishi Kosuke、Harmayani Eni、Pranoto Yudi、Sugahara Takuya
  • Journal Title: Molecules Volume: 22 Issue: 7 Pages: 1187-1187
  • DOI: 10.3390/molecules22071187
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Syntheses of cytotoxic novel arctigenin derivatives bearing halogen and alkyl groups on aromatic rings (2017)
  • Author(s): Yamauchi Satoshi、Wukirsari Tuti、Ochi Yoshiaki、Nishiwaki Hisashi、Nishi Kosuke、Sugahara Takuya、Akiyama Koichi、Kishida Taro
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 27 Issue: 17 Pages: 4199-4203
  • DOI: 10.1016/j.bmcl.2017.06.070
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Synthesis and inhibitory activity of 1,3-(adamantan-1(2)-yl)- imidazolidine-2,4,5-triones and 3,3'-(adamantan-1-yl)- bis(1-alkylimidazolidine-2,4,5-triones) (2017)
  • Author(s): D’yachenko Vladimir S.、Burmistrov Vladimir V.、Nishi Kosuke、Kim In-Hae、Butov Gennady M.
  • Journal Title: Chemistry of Heterocyclic Compounds Volume: 53 Issue: 10 Pages: 1080-1083
  • DOI: 10.1007/s10593-017-2174-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Immunostimulatory effect of aqueous extract of Coriandrum sativum L. seed on macrophages (2017)
  • Author(s): Ishida Momoko、Nishi Kosuke、Kunihiro Nanami、Onda Hiroyuki、Nishimoto Sogo、Sugahara Takuya
  • Journal Title: Journal of the Science of Food and Agriculture Volume: 97 Issue: 14 Pages: 4727-4736
  • DOI: 10.1002/jsfa.8341
  • Peer Reviewed
• [Presentation] DHA代謝物の抗アレルギー効果 (2020)
  • Author(s): 西 甲介, 金山佳毅, In-Hae Kim, 菅原卓也
  • Organizer: 第8回あしなが予防医学研究会
  • Invited
• [Presentation] 多価不飽和脂肪酸DHAの代謝物の抗アレルギー効果 (2020)
  • Author(s): 金山佳毅, In-Hae Kim, 菅原卓也, 西 甲介
  • Organizer: 日本農芸化学会中四国支部第56回講演会
• [Presentation] Anti-allergic effects of docosahexaenoyl ethanolamide (DHEA), a metabolite of docosahexaenoic acid (DHA) (2019)
  • Author(s): Kanayama Y, Kim IH, Sugahara T, Nishi K
  • Organizer: 7th International Conference on Food Factors(ICoFF2019) and 12th International Conference and Exhibition on Nutraceuticals and Functional Foods (ISNFF2019)
  • Int'l Joint Research
• [Presentation] Structure-anti-allergic activity relationships of long-chain fatty acids and their derivatives (2019)
  • Author(s): Kim IH, Kanayama Y, Sugahara T, Nishi K
  • Organizer: Allergy & Immune Modulation Symposium at 7th International Conference on Food Factors(ICoFF2019) and 12th International Conference and Exhibition on Nutraceuticals and Functional Foods (ISNFF2019)
  • Int'l Joint Research
• [Presentation] Anti-allergic effect of docosahexaenoyl ethanolamide (DHEA) on RBL-2H3 cells and pollinosis mice (2019)
  • Author(s): Kanayama Y, Kim IH, Sugahara T, Nishi K
  • Organizer: International Conference of Food Safety and Health 2019 (FSAH 2019)
  • Int'l Joint Research
• [Presentation] DHAとその代謝物の抗アレルギー効果 (2019)
  • Author(s): 西 甲介, 金山佳毅, In-Hae Kim, 菅原卓也
  • Organizer: 日本動物細胞工学会2019年度大会
• [Presentation] 魚油代謝物の抗アレルギー効果 (2019)
  • Author(s): 西 甲介
  • Organizer: 第23回生物機能研究会
  • Invited
• [Presentation] パッションフルーツ種子エタノール抽出物のIgE産生抑制効果 (2018)
  • Author(s): 菅原卓也・水崎 愛・石田萌子・西 甲介
  • Organizer: 第6回あしなが予防医学研究会
• [Presentation] 免疫系に作用する機能性食品成分の探索および作用機序の解明 (2018)
  • Author(s): 西 甲介
  • Organizer: 日本動物細胞工学会2017年受賞講演会
  • Invited
• [Presentation] コリアンダー（Coriandrum sativum L.）種子水溶性抽出物の免疫賦活活性に関する研究 (2017)
  • Author(s): 石田萌子・國廣菜波・西 甲介・恩田浩幸・西本壮吾・菅原卓也
  • Organizer: 第71回日本栄養・食糧学会大会
• [Presentation] クミン種子水溶性抽出物の免疫賦活効果に関する研究 (2017)
  • Author(s): 中山大輔・石田萌子・西 甲介・恩田浩幸・西本壮吾・菅原卓也
  • Organizer: 第71回日本栄養・食糧学会大会
• [Presentation] クミン種子水溶性抽出物の抗アレルギー作用に関する研究 (2017)
  • Author(s): 秦 麻琴・石田萌子・西 甲介・恩田浩幸・西本壮吾・菅原卓也
  • Organizer: 第71回日本栄養・食糧学会大会
• [Presentation] 食物アレルギーモデルマウスに対する黒酢の摂取効果 (2017)
  • Author(s): 石田萌子・粟根聖次・西 甲介・長野正信・橋口和典・藤井 暁・菅原卓也
  • Organizer: 日本動物細胞工学会2017年度大会
• [Presentation] クミン種子水溶性抽出物の脱顆粒抑制メカニズムの解明 (2017)
  • Author(s): 秦 麻琴・石田萌子・西 甲介・恩田浩幸・西本壮吾・菅原卓也
  • Organizer: 日本動物細胞工学会2017年度大会
• [Presentation] パクチー水溶性抽出物の抗アレルギー効果に関する研究 (2017)
  • Author(s): 北村優莉佳・石田萌子・西 甲介・恩田浩幸・西本壮吾・菅原卓也
  • Organizer: 日本動物細胞工学会2017年度大会
• [Presentation] クミン種子のマクロファージ活性化作用とその活性因子の同定 (2017)
  • Author(s): 中山大輔・石田萌子・西 甲介・恩田浩幸・西本壮吾・菅原卓也
  • Organizer: 日本動物細胞工学会2017年度大会
• [Presentation] 卵白由来リゾチームのマクロファージに対する抗炎症効果 (2017)
  • Author(s): 田頭歩佳・西 甲介・松本真弥・菅原卓也
  • Organizer: 日本動物細胞工学会2017年度大会
• [Presentation] プラセンタ水溶性抽出物の抗炎症効果 (2017)
  • Author(s): 横谷みゆき・西 甲介・佐々木義晴・菅原卓也
  • Organizer: 日本動物細胞工学会2017年度大会
• [Presentation] 柑橘果皮配合ヨーグルトの抗アレルギー効果 (2017)
  • Author(s): 菅原卓也・安永 翔・原 裕子・白石 敦・坂根由梨・鎌尾知行・竹澤由起・大橋裕一・菊池泰三・窪 千明・門田 歩・西 甲介
  • Organizer: 日本動物細胞工学会2017年度大会
• [Presentation] クミン種子水溶性抽出物がマクロファージ活性化に与える影響 (2017)
  • Author(s): 中山大輔・石田萌子・西 甲介・恩田浩幸・西本壮吾・菅原卓也
  • Organizer: 第32回日本香辛料研究会
• [Presentation] パクチー抽出物の脱顆粒抑制メカニズムの解明 (2017)
  • Author(s): 北村優莉佳・石田萌子・西 甲介・恩田浩幸・西本壮吾・菅原卓也
  • Organizer: 第32回日本香辛料研究会
• [Presentation] 食欲抑制作用を持つオレオイルエタノールアミドの生合成に与える胆汁酸の影響 (2017)
  • Author(s): 五十嵐美樹・西 甲介・Daniele Piomelli
  • Organizer: 日本脂質栄養学会第26回大会
• [Presentation] 食品成分によるアレルギー反応抑制効果 (2017)
  • Author(s): 西 甲介
  • Organizer: 日本農芸化学会中四国支部第26回若手研究者シンポジウム
  • Invited
• [Presentation] Suppressive effect of ethanol extract from mango (Mangifera indica L.) peel on IgE production in vitro and in vivo (2017)
  • Author(s): Ishida M., Sasaki T., Nishi K., Tamamoto T., Sugahara T.
  • Organizer: The 10th International Conference and Exhibition on Nutraceuticals & Functional Foods (ISNFF2017)
  • Int'l Joint Research
• [Presentation] Anti-inflammatory effect of lysozyme from hen egg white on macrophages (2017)
  • Author(s): Tagashira A., Nishi K., Mastumoto S., Sugahara T.
  • Organizer: The 10th International Conference and Exhibition on Nutraceuticals & Functional Foods (ISNFF2017)
  • Int'l Joint Research
• [Presentation] Nobiletin suppresses monocyte chemoattractant protein-1 (MCP-1) expression by regulating MAPK signaling in 3T3-L1 cells (2017)
  • Author(s): Sugahara T., Domen M., Yasunaga S., Nishi K., Ishida M., Kadota A.
  • Organizer: The 10th International Conference and Exhibition on Nutraceuticals & Functional Foods (ISNFF2017)
  • Int'l Joint Research
• [Presentation] Anti-allergic effect of Coriandrum sativum L. leaf extract (2017)
  • Author(s): Kitamura Y., Ishida M., Onda H., Nishimoto S., Nishi K., Sugahara T.
  • Organizer: The 10th International Conference and Exhibition on Nutraceuticals & Functional Foods (ISNFF2017)
  • Int'l Joint Research
• [Remarks] 愛媛大学大学院農学研究科生命機能学専攻動物細胞工学教育分野／食品機能学教育分野
  • URL: http://web-amb.agr.ehime-u.ac.jp/
• [Remarks] 愛媛大学農学部生命機能学科応用生命化学コース動物細胞工学教育分野
  • URL: https://www.agr.ehime-u.ac.jp/student/vital-function/lab/detail/lab608.html
• [Remarks] 愛媛大学農学部生命機能学科健康機能栄養科学特別コース食品機能学教育分野
  • URL: https://www.agr.ehime-u.ac.jp/student/vital-function/lab/detail/lab658.html
• [Remarks] 愛媛大学農学部動物細胞工学教育分野
  • URL: http://web-amb.agr.ehime-u.ac.jp/
• [Remarks] 日本動物細胞工学会奨励賞受賞報告（愛媛大学）
  • URL: https://www.ehime-u.ac.jp/post-72835/
• [Remarks] 日本動物細胞工学会奨励賞受賞報告（愛媛大学・英語）
  • URL: https://www.ehime-u.ac.jp/kosuke-nishi-receives-young-scientist-award-from-jaact/