Nobiletin (NOB), a polymethoxyflavonoid, is an effective anti-inflammatory and chemopreventive phytochemical found in citrus fruits. We compared the absorption and metabolism characteristics of NOB with those of luteolin (LT) in male SD rats. Each flavonoid (67.1 micromol/kg of body weight) was given separately by gastric intubation, and then concentrations were measured at 1, 4, and 24 hours after administration. In the digestive organs, NOB showed a notable tendency for localizing into the mucous membrane and muscularis from 1 to 4 hours, in contrast to LT, though both NOB and LT were completely excreted within 24 hours. Further, significant amounts of NOB were detected in the whole liver and kidney specimens, whereas LT accumulation was slight. Although serum concentrations of NOB from 1 to 4 hours were comparable to those of LT, urinary concentrations of LT were significantly higher from 4 to 24 hours. Following glucuronidase/sulfatase treatments of urinary materials, we detected 3 types of mono-demethylated NOB, including 3'-demethyl-NOB, and two di-demethylated types, as well as 3'-demethyl-NOB alone in serum samples using liquid chromatography-mass spectral analysis. Our results suggest that the metabolic properties of polymethoxyflavonoids are distinct from those of other general flavonoids, because of their wide distribution and accumulation in tissue.

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Muscle atrophy increases the production of reactive oxygen species and the expression of atrophy-related genes, which are involved in the ubiquitin -proteasome system. In the present study, we investigated the effects of b-carotene on oxidative stress (100 mM-H 2 O 2 )-induced muscle atrophy in murine C2C12 myotubes. b-Carotene (10 mM) restored the H 2 O 2 -induced decreased levels of myosin heavy chain and tropomyosin (P,0·05, n 3) and decreased the H 2 O 2 -induced increased levels of ubiquitin conjugates. b-Carotene reduced the H 2 O 2 -induced increased expression levels of E3 ubiquitin ligases (Atrogin-1 and MuRF1) and deubiquitinating enzymes (USP14 and USP19) (P,0·05, n 3) and attenuated the H 2 O 2 -induced nuclear localisation of FOXO3a. Furthermore, we determined the effects of b-carotene on denervation-induced muscle atrophy. Male ddY mice (8 weeks old, n 30) were divided into two groups and orally pre-administered micelle with or without b-carotene (0·5 mg once daily) for 2 weeks, followed by denervation in the right hindlimb. b-Carotene was further administered once daily until the end of the experiment. At day 3 after denervation, the ratio of soleus muscle mass in the denervated leg to that in the sham leg was significantly higher in b-carotene-administered mice than in control vehicle-administered ones (P,0·05, n 5). In the denervated soleus muscle, b-carotene administration significantly decreased the expression levels of Atrogin-1, MuRF1, USP14 and USP19 (P,0·05, n 5) and the levels of ubiquitin conjugates. These results indicate that b-carotene attenuates soleus muscle loss, perhaps by repressing the expressions of Atrogin-1, MuRF1, USP14 and USP19, at the early stage of soleus muscle atrophy.

We previously reported that auraptene (7-geranyloxycoumarin; AUR), a coumarin that occurs widely in citrus fruit, has been shown to be a promising cancer-preventive agent in several rodent models. However, its bioavailability and metabolism have not been investigated. In this study, we compared the metabolism characteristics of AUR with those of 7-ethoxycoumarin (ETC) in male Sprague Dawley rats. Each (500 micromol/kg body weight) was given separately by a single gastric intubation procedure, and digestive tract, liver, and kidney were removed at 1, 4, and 24 h after administration. The localization profiles of AUR and ETC in the gastrointestinal tract were similar. However, AUR, in contrast to ETC, showed significant localization in the liver from 1 to 4 h. Treatments of serum and urinary samples with glucuronidase/sulfatase led to the detection of significant amounts of umbelliferone (7-hydroxycoumarin; UMB), and serum and urinary concentrations of UMB following ETC administration were significantly higher than with AUR administration. Our results suggest that AUR, which bears a geranyloxyl side chain, has a longer life span than ETC, and this property may be associated with its previously reported chemopreventive and xenobiotics metabolizing activities.

SummaryIn this study, a dietary survey for 3 weekdays of young unmarried subjects [workers and students, 159 males and 160 females, ages 18-19 y (17.2%), 20-24 y (56.2%), 25-29 y (18.6%), 30-34 y (6.7%) and 35 y-(1.3%)] was performed. We evaluated the intake of green and yellow vegetables in this survey and determined the carotenoids ( ␤ -carotene, ␣ -carotene, lycopene, ␤ -cryptoxanthin, and lutein ϩ zeaxanthin) in 15 kinds of green and yellow vegetables frequently consumed. The carotenoid intake of each subject was calculated from the intake of these vegetables and the amount of carotenoid. Moreover, we studied the intake of protein, fat, and dietary fiber, and investigated its relationship to the intake of vegetables. The mean green and yellow vegetable intake/d in all subjects was 60.5 Ϯ 58.7 g, much lower than the recommended level [120 g/d, (Health Japan 21 by Japanese Ministry of Health, Labour and Welfare)]. The intake of green and yellow vegetables was greater in females than males, and in workers than students. In all subjects, the mean total carotenoid intake/d was 2,852.8 Ϯ 2,354.3 g. In the total intake of carotenoids, there was no difference between males and females; however, the intake was greater in workers than in students. The intake of ␤ -carotene and ␣ -carotene was greater in males than females. However, the intake of ␤ -cryptoxanthin, lycopene, and lutein ϩ zeaxanthin was greater in females than males. The group with the low green and yellow vegetable intake had not only a low carotenoid intake, but also a low intake of protein, fat, and dietary fiber. Therefore, it was suggested that carotenoid absorption may be affected by a low intake of protein, fat, and dietary fiber.