The hypocholesterolemic action of eritadenine, a compound found in the mushroom Lentinus edodes, was investigated in relation to its influence on phospholipid metabolism in the liver of rats fed diets containing different amounts of choline chloride (0, 2 and 8 g/kg diet). The time-dependent effect of eritadenine supplementation was also investigated. Eritadenine supplementation (50 mg/kg diet) significantly decreased the phosphatidylcholine (PC):phosphatidylethanolamine (PE) ratio in liver microsomes and the S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) ratio in the liver, in addition to the plasma cholesterol concentration, irrespective of dietary choline levels. There was a significant correlation between the plasma cholesterol concentration and the liver microsomal PC:PE ratio. Although eritadenine caused fatty liver when added to the diets containing 0 or 2 g/kg choline chloride, a high level (8 g/kg) of choline chloride fully prevented the eritadenine-induced fatty liver without diminution of hypocholesterolemic action. Both the PC:PE ratio and the SAM:SAH ratio decreased significantly prior to the decrease in the plasma cholesterol concentration (1 d vs. 2 d after) in response to eritadenine supplementation, supporting the hypothesis that the alteration of hepatic phospholipid metabolism may be a cause of the hypocholesterolemic action of eritadenine. These observations suggest that the essential hypocholesterolemic action of eritadenine might be associated with a modification of hepatic phospholipid metabolism rather than with the PC deficiency, due to the inhibition of PE N-methylation.

SummaryWe 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)-␣ 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-␣ 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. Key Words D -galactosamine, liver injury, shekwasha, Citrus depressa , flavonoids Fruits and vegetables are important as sources of several nutrients such as vitamins, minerals and dietary fibers. Fruits and vegetables also contain a variety of constituents, which are characteristic of the species of plant. It is widely recognized that relatively high intakes of fruits and vegetables are desirable for prevention of diseases and maintenance of healthy conditions ( 1 ). Previously we reported that several kinds of fruit had suppressive effects on D -galactosamine (GalN)-induced liver injury in rats when various kinds of lyophilized fruit were added to the diet ( 2 ). Furthermore, recently we found that some fruit juices, e.g., camu-camu and shekwasha, also had suppressive effects on GalNinduced liver injury in rats, and we identified the active compound (unpublished data). These findings indicate that certain fruits (and possibly vegetables) have a hepatoprotective effect in addition to nutritional effects.Since the liver is the central organ of many types of metabolism, the hepatoprotective effect of foods is worthwhile to investigate in detail, not only from the viewpoint of food science but also from the viewpoint of nutrition.In the present study, we attempted to isolate the constituent(s) res...

No abstract

No abstract