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The effect of a novel tocotrienol prodrug on nonalcoholic fatty liver disease in vitro and in vivo

Research Project

Project/Area Number 16K18971
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionFukuoka University

Principal Investigator

Watase Daisuke  福岡大学, 薬学部, 助教 (00580200)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsプロドラッグ / NAFLD / 脂肪肝 / 医療薬剤学
Outline of Final Research Achievements

2R-γ-Tocotrienyl N, N-dimethylglycinate hydrochloride (γ-T3DMG) is a prodrug of γ-tocotrienol (γ-T3) with high water-solubility and stability to oxidation, it could effectively deliver γ-T3 in the rat liver. The present study investigated the therapeutic effects of γ-T3DMG on a fatty liver model in vitro and in vivo. γ-T3DMG significantly suppressed levels of triglyceride (TG) and total cholesterol on a fatty liver model using HepG2 cells. In addition, γ-T3DMG significantly suppressed plasma ALT activities and plasma TG concentrations in TSOD mice with spontaneously developed obesity. These results indicated that γ-T3DMG had a beneficial effect on hepatic steatosis, thus could be a promising candidate for the treatment of NAFLD.

Academic Significance and Societal Importance of the Research Achievements

本研究室で開発した2R-γ-Tocotrienyl N,N-dimethylglycinate hydrochloride (γ-T3DMG) はγ-トコトリエノールを肝臓へ効率的に送達する水溶性プロドラッグである。本研究ではin vitro及びin vivo脂肪肝モデルを用いてγ-T3DMGが優れた脂肪肝抑制効果を有することを明らかにした。よって本研究によりγ-T3DMGを新規のNAFLD治療薬として臨床応用するための基盤を確立した。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2018 2017

All Presentation (3 results)

  • [Presentation] γ-トコトリエノールエステル型プロドラッグによる脂肪肝抑制効果2018

    • Author(s)
      渡瀬大輔、長田-赤穂菜美、楠田真理子、寺田一樹、後藤将太朗、松永和久、加留部善晴、髙田二郎
    • Organizer
      第29回ビタミンE研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] In vivo脂肪肝モデルにおけるγ-トコトリエノールエステル型プロドラッグによる脂肪肝抑制効果の評価2018

    • Author(s)
      平田茉莉花、渡瀬大輔、長田(赤穂)菜美、平野(楠田)真理子、寺田一樹、山川博文、後藤将太朗、松永和久、加留部善晴、髙田二郎
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] γ-トコトリエノールエステル誘導体の in vitro脂肪肝モデルにおける効果2017

    • Author(s)
      渡瀬 大輔、長田-赤穂 菜美、楠田 真理子、寺田 一樹、 松永 和久、加留部 善晴、髙田 二郎
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      宮城県仙台市
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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