Enzymatic synthesis of novel rutinoside and its neuroprotective properties

• Project/Area Number: 15K07426
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Shinshu University
• Principal Investigator: Katayama Shigeru 信州大学, 学術研究院農学系, 准教授 (30443922)
• Co-Investigator(Renkei-kenkyūsha): MAKABE Hidefumi 信州大学, 学術研究院農学系, 教授 (90313840) ; Furuya Shigeki 九州大学(連合), 農学研究科(研究院), 教授 (00222274)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 配糖体 / 神経変性疾患 / 神経栄養因子 / BDNF / 神経新生 / フェルラ酸 / アストロサイト / 神経細胞 / 認知能力 / 老化促進モデルマウス / 神経細胞保護効果 / Hsp70

Outline of Final Research Achievements

Phenolic compounds are known to be efficient antioxidants; however, their use is often limited by their weak solubility either in hydrophilic or hydrophobic formulations. Thus, glycosylation of hydrophilic compound can be a potent strategy to alter their solubility. In the present study, we synthesized new phenol compounds using rutinase as transglycosidative enzyme and investigated its neuroprotective properties. Rutinosides were prepared using the reverse reaction of hydrolysis by rutinase. More than 10 kinds of phenolic compounds were successfully glycosylated by the reverse reaction of rutinase. The solubility and Caco-2 permeability of ferulic acid rutinoside (FAR) significantly improved by glycosylation with rutinose. FAR induced the upregulation of neuroprotection-related genes such as BDNF and NGF in mouse primary astrocytes. These results suggest that transglycosylation using rutinose is an effective method for preparing novel neuroprotective phenolic compounds.

Research Products

• [Journal Article] Kale supplementation up-regulates HSP70 and suppresses cognitive decline in a mouse model of accelerated senescence (2018)
  • Author(s): Kushimoto Shoko、Uchibori Yuki、Yanai Shuichi、Makabe Hidefumi、Nakamura Soichiro、Katayama Shigeru
  • Journal Title: Journal of Functional Foods Volume: 44 Pages: 292-298
  • DOI: 10.1016/j.jff.2018.03.011
  • Peer Reviewed
• [Journal Article] Rutinosylated Ferulic Acid Attenuates Food Allergic Response and Colitis by Upregulating Regulatory T Cells in Mouse Models (2017)
  • Author(s): Katayama Shigeru、Ohno Fumiaki、Mitani Takakazu、Akiyama Hiroshi、Nakamura Soichiro
  • Journal Title: Journal of Agricultural and Food Chemistry Volume: 65 Issue: 49 Pages: 10730-10737
  • DOI: 10.1021/acs.jafc.7b03933
  • Peer Reviewed
• [Journal Article] Effects of Sesaminol Feeding on Brain Aβ Accumulation in a Senescence-Accelerated Mouse-Prone 8 (2016)
  • Author(s): Katayama, S., Sugiyama, H., Kushimoto, S., Uchiyama, Y., Hirano, M., Nakamura, S
  • Journal Title: J. Agric. Food Chem. Volume: 64 Issue: 24 Pages: 4008-4013
  • DOI: 10.1021/acs.jafc.6b01237
  • Peer Reviewed
• [Presentation] フェルラ酸ルチノシドのBDNF産生促進作用とCaco-2細胞透過性 (2018)
  • Author(s): 松本果楠子，三谷塁一，中村宗一郎，片山茂
  • Organizer: 日本食品化学学会第24回総会・学術大会
• [Presentation] Enzymatic synthesis of novel rutinoside using rutinase and its functional properties (2017)
  • Author(s): Kanako Matsumoto, Shigeru Katayama, Fumiaki Ohno, Takakazu Mitani, Soichiro Nakamura
  • Organizer: III International Conference on Food Chemistry & Technology
  • Int'l Joint Research
• [Presentation] Long-term dietary intake of kale extract attenuates cognitive impairment in senescence-accelerated mouse prone 8 (2017)
  • Author(s): Shoko Kushimoto, Shigeru Katayama, Takakazu Mitani, Tomohiro Ohno, Soichiro Nakamura
  • Organizer: III International Conference on Food Chemistry & Technology
  • Int'l Joint Research / Invited
• [Presentation] Brain Health Benefits by Natural Dietary Bioactive Compounds: A Mechanistic Exploration (2016)
  • Author(s): Shigeru Katayama
  • Organizer: 2016 International Symposium and Annual Meeting of The KSABC
  • Place of Presentation: ICC JEJU, Korea
  • Year and Date: 2016-06-16
  • Int'l Joint Research / Invited
• [Presentation] 大豆由来塩基性ペプチドのBDNF産生促進効果 (2016)
  • Author(s): 清水綾乃，有村美紗，前渕元宏，三谷塁一，片山茂，中村宗一郎
  • Organizer: 日本食品化学学会 第22回総会・学術大会
  • Place of Presentation: 高知市文化プラザかるぽーと（高知県高知市）
  • Year and Date: 2016-06-02
• [Presentation] 食物アレルギーおよび大腸炎モデルマウスに対するフェルラ酸ルチノシドの免疫調節作用 (2016)
  • Author(s): 片山茂、大野史晃、三谷塁一、中村宗一郎
  • Organizer: 第70回日本栄養・食糧学会大会
  • Place of Presentation: 武庫川女子大学（兵庫）
  • Year and Date: 2016-05-13