Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats
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概要
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We attempted to isolate the constituent(s) responsible for the suppressive effect of the juice of shekwasha, a citrus produced in Okinawa Prefecture, on D-galactosamine (GalN)-induced liver injury in rats. Liver injury-suppressive activity, as assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, was found only in the fraction that was extracted with n-hexane when three fractions were added to the diet and fed to rats. Of five compounds isolated from the n-hexane-soluble fraction by silica gel column chromatography, three compounds had liver injury-suppressive effects when five compounds were singly force-fed to rats at a level of 300 mg/kg body wt 4 h before the injection with GalN. The structures of the three active compounds were determined as 3,4,5,6,7,8-hexamethoxyflavanone (citromitin), 4,5,6,7,8-pentamethoxyflavone (tangeretin) and 3,4,5,6,7,8-hexamethoxyflavone (nobiletin), which are known flavonoids mainly existing in citrus. Nobiletin, the most important compound in the n-hexane-soluble fraction, also had suppressive effects on liver injuries induced by carbon tetrachloride, acetaminophen and GalN/lipopolysaccharide (LPS) in addition to liver injury induced GalN. Nobiletin suppressed GalN/LPS-induced increases in plasma tumor necrosis factor (TNF)-α and nitric oxide (NO) concentrations and hepatic mRNA levels for inducible NO synthase and DNA fragmentation. These results suggest that nobiletin suppressed GalN/LPS-induced liver injury at least by suppressing the production of both TNF-α and NO. The results obtained here indicate that the hepatoprotective effect of shekwasha juice is mainly ascribed to several polymethoxy flavonoids included in the juice.
- 2010-02-01
著者
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KAWAGUCHI Takumi
Department of Digestive Disease Information & Research
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Akachi Toshiyuki
The United Graduate School Of Agricultural Science Gifu University
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SHIINA Yasuyuki
Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University
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OHISHI Yayoi
Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University
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KAWAGISHI Hirokazu
Graduate School of Science and Technology, Shizuoka University
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MORITA Tatsuya
Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University
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MORI Makoto
Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University
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SUGIYAMA Kimio
Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University
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Kawaguchi Takumi
Dep. Of Applied Biological Chemistry Fac. Of Agriculture Shizuoka Univ.
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Kawaguchi Takumi
Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University
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Sugiyama Kimio
静岡大学 農 応用生物化学科
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Sugiyama Kimio
静岡大学 農学部応用生物化学
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Ohishi Yayoi
Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University
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Morita Tatsuya
静岡大学 農学部応用生物化学
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Morita Tatsuya
Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University
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Shiina Yasuyuki
Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University
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Kawagishi Hirokazu
Graduate School Of Science And Technology Shizuoka University
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Kawagishi Hirokazu
Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University
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Kawagishi Hirokazu
Graduate School Of Sci. And Technol. Shizuoka Univ.
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Mori Makoto
Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University
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杉山 公男
Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University
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Sugiyama Kimio
岐阜大学 連合農学研究科
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Morita Tatsuya
岐阜大学 連合農学研究科
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Sugiyama Kimio
Department Of Applied Biochemistry Faculty Of Agriculture Shizuoka University
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杉山 公男
静岡大学 農学部応用生物化学科
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Hayashi Kanako
Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University
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Mori Makoto
Department Of 1st Oral Surgery School Of Dentistry Aichi-gakuin University
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赤地 利幸
大和製罐株式会社 総合研究所
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SUGIYAMA Kimio
Department of Agricultural Chemistry, Faculty of Agriculture, Shizuoka University
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