炎症誘導性脂質メディエーター合成系を標的とした小豆の新規食品機能性

• Project/Area Number: 22K17833
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Okayama Prefectural University
• Principal Investigator: 津嘉山 泉 岡山県立大学, 保健福祉学部, 助教 (30823249)
• Project Period (FY): 2022-04-01 – 2026-03-31
• Project Status: Granted (Fiscal Year 2023)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2025: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2024: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 抗炎症効果 / mPGES-1 / 5-LOX / ミクロソーム型PGE合成酵素－1 / 5－リポキシゲナーゼ / ミクロソーム型PGE合成酵素-1 / 5-リポキシゲナーゼ

Outline of Research at the Start

n-6系脂肪酸アラキドン酸由来の種々の生理活性脂質は，生体内の恒常性維持に重要な一方で，過剰な産生により，様々な疾患の惹起や重症化に関与するものがある。なかでも，炎症誘導性脂質メディエーターのプロスタグランジン(PG)E2とロイコトリエン (LT)類は，強力な炎症誘導因子として働く。本研究では，小豆皮の機能性について，これら炎症誘導性脂質メディエーター合成系酵素に焦点をあて，①機能性成分の単離・同定，②酵素学的・病態生理学的な解析，③生体投与における安全性の検証に取り組み，安全で，広範な炎症性疾患に有効な，小豆皮由来成分の新規食品機能性の解明を目指す。

Outline of Annual Research Achievements

本研究では、小豆皮より、炎症誘導性脂質メディエーターを標的とした、安全で副作用を回避した新規食品機能性成分とその効果を明らかにし、慢性炎症予防への貢献を目指している。慢性炎症の誘導や促進に関わる炎症誘導性脂質メディエーターのプロスタグランジン(PG)E2やロイコトリエン(LT)の合成系を標的とした食品機能性を探索する中で、ミクロソーム型PGE合成酵素-1 (mPGES-1)と5-リポキシゲナーゼ (5-LOX)に対する二重阻害効果を見出した。機能性成分の単離同定を目指し、逆相クロマトグラフやゲル浸透クロマトグラフなどにより分画と精製を試みた。その結果、機能性成分は比較的極性の低い化合物である可能性が示唆された。

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

本年度は、留学により大部分の期間本研究を中断していた。そのため、機能性成分の単離と精製を進めているものの、当初予定していたよりも時間がかかっており、進捗が遅れている。

Strategy for Future Research Activity

今年度と同様に、小豆皮のmPGES-1/5-LOX二重阻害作用を示す成分の単離同定を進める。また、酵素反応速度論に基づく阻害様式や効果の比較を行い、酵素特異性を検討するとともに、培養細胞を用いて、成分添加による炎症関連因子の発現動態を解析し、抗炎症・抗腫瘍効果を検討する予定である。

Research Products

• [Journal Article] A thickening agent using Dioscorea japonica powder exhibits suitable properties for people with dysphagia. (2023)
  • Author(s): Yuka Konoike, Izumi Tsukayama, Mei Oji, Takayo Kawakami, Kayoko Ishii, Toshiko Suzuki-Yamamoto.
  • Journal Title: Foods Volume: 12 Issue: 21 Pages: 3943-3943
  • DOI: 10.3390/foods12213943
  • Peer Reviewed / Open Access
• [Journal Article] Malabaricone C derived from nutmeg inhibits arachidonate 5-lipoxygenase activity and ameliorates psoriasis-like skin inflammation in mice (2022)
  • Author(s): Tsukayama Izumi、Kawakami Yuki、Tamenobu Asako、Toda Keisuke、Maruoka Saya、Nagasaki Yuki、Mori Yoshiko、Sawazumi Risa、Okamoto Kensuke、Kanzaki Keita、Ito Hideyuki、Takahashi Yoshitaka、Miki Yoshimi、Yamamoto Kei、Murakami Makoto、Suzuki-Yamamoto Toshiko
  • Journal Title: Free Radical Biology and Medicine Volume: 193 Pages: 1-8
  • DOI: 10.1016/j.freeradbiomed.2022.09.028
  • Peer Reviewed / Open Access
• [Journal Article] Lipid profiling reveals the presence of unique lipid mediators in human milk from healthy and mastitic subjects (2022)
  • Author(s): Nagasaki Yuki、Kawai Erika、Maruoka Saya、Osumi Miho、Tsukayama Izumi、Kawakami Yuki、Takahashi Yoshitaka、Okazaki Yuka、Miki Yoshimi、Taketomi Yoshitaka、Yamamoto Kei、Murakami Makoto、Suzuki-Yamamoto Toshiko
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 630 Pages: 84-91
  • DOI: 10.1016/j.bbrc.2022.09.051
  • Peer Reviewed / Open Access
• [Presentation] Malabaricone C derived from nutmeg inhibits arachidonate 5-lipoxygenase activity ameliorating murine psoriasis-like skin inflammation and OVA-induced allergic airway inflammation. (2023)
  • Author(s): Toshiko Suzuki-Yamamoto, Izumi Tsukayama, Yuki Kawakami, Asako Tamenobu, Keisuke Toda, Saya Maruoka, Hideyuki Ito, Yoshitaka Takahashi, Yoshimi Miki, Makoto Murakami.
  • Organizer: 63rd International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] Inhibition of arachidonate 5-lipoxygenase and amelioration of psoriasis-like skin symptoms by malabaricone C derived from nutmeg. (2022)
  • Author(s): Izumi Tsukayama, Yuki Kawakami, Asako Tamenobu, Saya Maruoka, Yoshimi Miki, Makoto Murakami, Toshiko Suzuki-Yamamoto.
  • Organizer: 17th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
  • Int'l Joint Research
• [Presentation] Lipid profiling reveals the presence of unique lipid mediators in human milk from healthy and mastitic subjects. (2022)
  • Author(s): Yuki Nagasaki, Erika Kawai, Saya Marukoka, Miho Osumi, Izumi Tsukayama, Yuka Okazaki, Yoshimi Miki, Kei Yamamoto, Makoto Murakami, Toshiko Suzuki-Yamamoto.
  • Organizer: 17th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
  • Int'l Joint Research
• [Presentation] Diosgenin, a natural steroidal saponin, suppresses COX-2 and mPGES-1 via the glucocorticoid receptor and improves LPS-induced liver injury in mice. (2022)
  • Author(s): Izumi Tsukayama, Nana Hojo, Takuto Mega, Keisuke Toda, Yuki Kawakami, Yoshitaka Takahashi, Toshiko Suzuki-Yamamoto.
  • Organizer: 22nd IUNS-ICN International Congress of Nutrition
  • Int'l Joint Research
• [Presentation] Comparative profile of free fatty acids and the metabolites between different species and search for the critical enzymes to the lipid composition. (2022)
  • Author(s): Saya Maruoka, Yuki Nagasaki, Erika Kawai, Miho Oosumi, Izumi Tsukayama, Yoshimi Miki, Makoto Murakami, Kei Yamamoto, Toshiko Suzuki-Yamamoto.
  • Organizer: 22nd IUNS-ICN International Congress of Nutrition
  • Int'l Joint Research
• [Presentation] Assessment of functional food Dioscorea japonica paste as a thickened liquid for elderly with dysphagia. (2022)
  • Author(s): Yuka Konoike, Izumi Tsukayama, Mei Oji, Takayo Kawakami, Kayoko Ishii, and Toshiko Suzuki-Yamamoto.
  • Organizer: 22nd IUNS-ICN International Congress of Nutrition
  • Int'l Joint Research