Effect of flavanone glycosides on myelin repair

• Project/Area Number: 25830056
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Keio University
• Principal Investigator: SEIWA Chika 慶應義塾大学, 医学部, 特任助教 (60399459)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: OPC / フラボノイド / Ddx54 / ミエリン / ヘスペリジン / オリゴデンドロサイト前駆細胞 / 増殖

Outline of Final Research Achievements

We previously demonstrated that demyelination was prevented by herbal medicine chinpi, a type of dried ctrus peel and showed that RNA helicase Ddx54 protein interact with myelin basic protein (MBP) mRNA. Furthermore, Ddx54 knockdown cased a significant decrease on the MBP, suggesting play an important role in CNS myelination.
In this study, we have investigated whether administration of hesperidin (one of the major active constitution of chinpi) accelerate Ddx54-expressing OPCs proliferation. We observed that BrdU incorporation rate when OPCs were cultured in the presence of hesperidin (10uM) for 24 hour. Ddx54 positive OPCs were markedly increased by treatment of hesperidin in comparison with control cultures. The stimulation of functional OPCs with hesperidin could serve as a valuable tool for repairing functional damage caused by demyelinating diseases suggesting a possible therapeutic herbal medicine.

Research Products

• [Journal Article] Phase separation of myelin sheath in Triton X-114 solution: predominant localizaion of the 21.5-kDa isoform of myelin basic protein in the lipid raft-associated domain. (2014)
  • Author(s): Uruse, M., Yamamoto, M., Sugawa, M., Matsuura, K., Sato, Y., Seiwa, C., Watanabe, K., Aiso, T. and Asou, H.
  • Journal Title: J. Neurochem. Volume: 155 Issue: 4 Pages: 265-271
  • DOI: 10.1093/jb/mvu005
  • Peer Reviewed
• [Journal Article] A DEAD-box RNA helicase Ddx54 protein in oligodendrocytes is indispensable for myelination in the central nervous system (2013)
  • Author(s): Zhan R, et al.
  • Journal Title: Journal of Neuroscience Research Volume: 91 Issue: 3 Pages: 335-348
  • DOI: 10.1002/jnr.23162
  • Peer Reviewed
• [Presentation] チンピ（ウンシュウミカン果皮）による脱髄回復効果の作用機序解明 (2014)
  • Author(s): 阿相皓晃、清和千佳
  • Organizer: 第12回日本機能性食品医用学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-14
• [Presentation] OPCの増殖を促すヘスペリジン/ナリルチン（チンピの有効成分）の分子機構にはプレニル化が関与する (2013)
  • Author(s): 清和千佳、山本雅浩、植木俊之、阿相皓晃
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] DEAD-box RNA helicase Ddx54は中枢でのミエリン形成に必須である (2013)
  • Author(s): 山本雅浩、植木俊之、吉岡望、森崎博実、清和千佳、鶴尾吉宏、阿相皓晃
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館（京都）