Rapid and convenient method for preparing aurapten-enriched product from hassaku peel oil: implications for cancer-preventive food additives.

Aurapten (7-geranyloxycoumarin) has been reported to be an effective inhibitor of chemical carcinogenesis in some rodent models. In the present study, a method for preparing an aurapten-enriched agricultural product has been established. Out of 17 Rutaceae varieties, the aurapten content in hassaku (Citrus hassaku Hort ex Y. Tanaka) fruit peel was marked, as well as that in natsumikan (C. natsudaidai) and grapefruit (C. paradisi). The aurapten content in hassaku peel was most abundant in April. Hassaku fruit peel oil, which was dissolved by heating precipitates including aurapten which had formed after freezing the peel oil at -20 degrees C, was used. After adsorbing aurapten from peel oil onto synthetic adsorbent SP70, the adsorbent was washed with 40% (v/v) ethanol in water to remove essential oils and pigments remaining on the adsorbent. Aurapten was then eluted with 80% (v/v) ethanol. In a laboratory-scale test, the recovery rates of aurapten and total carotenoids from the eluates were 74.3 and 4.6%, respectively. In a pilot-scale test, the recovery rate of aurapten in the aurapten-enriched preparation from dissolved hassaku oil was 91.0%, and its concentration was 64.1% (w/w). When stored for 180 days under sunlight, aurapten in powder form remained at 88.0-89.0% of the initial level, but only 31.3-43.8% in ethanol. The stability of aurapten in the aurapten-enriched preparation was higher than that of purified aurapten. These results suggest that aurapten is readily recovered from hassaku peel oil using SP70, and thus may be used as a food additive.

Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolin.

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.

Metabolism and absorption of auraptene (7-geranyloxylcoumarin) in male SD rats: comparison with 7-ethoxycoumarin.

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.

Effects of gamma-terpinene on lipid concentrations in serum using Triton WR1339-treated rats.

We studied lipid metabolism to evaluate the effects of gamma-terpinene on suppression of increases in serum lipid concentrations using Triton WR1339-treated rats. At 6 hr after Triton WR1339 injection, the total cholesterol and triglyceride concentrations in the gamma-terpinene group underwent statistically significant decreases (18.3 and 30.3%, respectively) compared with those of the Triton-treated group.

Antioxidative effect of citrus essential oil components on human low-density lipoprotein in vitro.

We studied the antioxidative action to evaluate the effect of citrus essential oil components on human LDL in vitro. Among the authentic volatile compounds tested, gamma-terpinene showed the strongest antioxidative effect, and inhibited both the Cu(2+)-induced and AAPH-induced oxidation of LDL. gamma-Terpinene added after 30 min (mid-lag phase) and 60 min (propagation phase) of incubation of LDL with Cu(2+) inhibited LDL oxidation.