Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Autor: Yayoi Ohishi, Toshiyuki Akachi, Tatsuya Morita, Makoto Mori, Takumi Kawaguchi, Yasuyuki Shiina, Hirokazu Kawagishi, Kimio Sugiyama
Rok vydání: 2010
Předmět:
Zdroj: Journal of Nutritional Science and Vitaminology. 56:60-67
ISSN: 1881-7742
0301-4800
DOI: 10.3177/jnsv.56.60
Popis: 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)-alpha 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-alpha 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.
Databáze: OpenAIRE