2022 Fiscal Year Final Research Report
The effect of a novel tocotrienol prodrug on progression from NAFLD to NASH
| Project/Area Number |
18K14970
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Fukuoka University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Keywords | プロドラッグ |
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| 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 progression from NAFLD to NASH. γ-T3DMG significantly suppressed mRNA levels of IL-1β on in vitro NASH model prepared by adding TNF-α to hepatocytes derived from high-fat diet-fed TSOD mice. In addition, γ-T3DMG significantly suppressed mRNA levels of α-SMA and TGF-β1 on in vitro NASH model prepared by loading human hepatic stellate cell line LX-2 cells with free fatty acid. These results indicated that γ-T3DMG had a beneficial effect on progression from NAFLD to NASH, thus could be a promising candidate for the treatment of NASH.
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| Free Research Field |
薬物送達学
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| 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。本研究ではいくつかのin vitro NASHモデルを用いてγ-T3DMGが優れたNASH進展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NASH治療薬として臨床応用するための基盤を確立した。
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