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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18971
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Fukuoka University
• Principal Investigator: Watase Daisuke 福岡大学, 薬学部, 助教 (00580200)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: プロドラッグ / NAFLD / 脂肪肝

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.

Free Research Field

薬物送達学

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。