amarouciaxanthin-a and fucoxanthinol

Dietary fucoxanthin has been reported to exert several physiological functions, and fucoxanthinol is considered to be the primary active metabolite of fucoxanthin. However, there is no information about the pharmacokinetics of fucoxanthinol in human subjects. In the present study, eighteen human volunteers were orally administered kombu extract containing 31 mg fucoxanthin, and their peripheral blood was collected 5 min before and 0·5, 1, 2, 4, 8 and 24 h after the treatment. Plasma fucoxanthinol concentrations were measured by HPLC, and the pharmacokinetics of fucoxanthinol were as follows: maximum concentration, 44·2 nmol/l; time at maximum concentration, 4 h; terminal half-time, 7·0 h; area under the curve (AUC) for 1-24 h, 578·7 nmol/l × h; AUC(∞), 663·7 nmol/l × h. In addition to fucoxanthinol, we also attempted to detect amarouciaxanthin A, a hepatic metabolite of fucoxanthinol, using HPLC, but it was not present in the volunteers' plasma. On the other hand, a peak that was suspected to represent the cis-isomer of fucoxanthinol was found in the HPLC chromatogram. By comparing the present results with those of a previous study using mice, we found that the bioavailability and metabolism of fucoxanthinol differ between human subjects and mice.

Topics: Adult; beta Carotene; Biological Availability; Biotransformation; Chromatography, High Pressure Liquid; Dietary Supplements; Female; Half-Life; Humans; Laminaria; Male; Middle Aged; Spectrophotometry; Xanthophylls; Young Adult

Administered carotenoid fatty acid esters are thought to be hydrolyzed to their free forms and absorbed into the body, and information on the tissue distribution of carotenoid fatty acid esters has been limited. Fucoxanthin, a marine carotenoid, exhibits various health benefits, including anti-diabetic and anti-obesity effects. However, fucoxanthin metabolism in mammals remains unclear. Herein, we investigated the fatty acid esters of fucoxanthin metabolites, fucoxanthinol and amarouciaxanthin A, in the tissues of male C57BL/6J mice fed a fucoxanthin-containing diet for one week. Fucoxanthinol and amarouciaxanthin A-3-esters accumulated abundantly in the liver and epididymal white adipose tissue, respectively. These esters were less detectable in the serum and other tissues. Therefore, it is suggested that fucoxanthinol and amarouciaxanthin A are partially acylated in the liver and epididymal white adipose tissue after being transported through the body as their free forms. This study presents a novel carotenoid metabolic pathway in mammals.

Topics: Animals; Carotenoids; Male; Mammals; Mice; Mice, Inbred C57BL; Tissue Distribution

The pharmacokinetics of dietary fucoxanthin, one of the xanthophylls in brown sea algae, is little understood. In the present study, mice were orally administered fucoxanthin, and the distribution and accumulation of fucoxanthin and its metabolites fucoxanthinol and amarouciaxanthin A were measured in the plasma, erythrocytes, liver, lung, kidney, heart, spleen and adipose tissue. In a single oral administration of 160 nmol fucoxanthin, fucoxanthinol and amarouciaxanthin A were detectable in all specimens tested in the present study, but fucoxanthin was not. The time at maximum concentration (Tmax) of these metabolites in adipose tissue was 24 h, while the Tmax in the others was 4 h. The area under the curve to infinity (AUCinfinity) of fucoxanthinol in the liver was the highest value (4680 nmol/g x h) among the tissues tested in the present study, while the AUCinfinity of amarouciaxanthin A in adipose tissue was the highest value (4630 nmol/g x h). In daily oral administration of 160 nmol fucoxanthin for 1 week, fucoxanthin was also detectable in the tissues even at a low concentration. The amount of fucoxanthinol was 123 nmol/g in the heart and 85.2 nmol/g in the liver. Amarouciaxanthin A in the adipose tissue was distributed at a concentration of 97.5 nmol/g. These results demonstrate that dietary fucoxanthin accumulates in the heart and liver as fucoxanthinol and in adipose tissue as amarouciaxanthin A.

Topics: Adipose Tissue; Administration, Oral; Animals; beta Carotene; Chromatography, High Pressure Liquid; Liver; Male; Mice; Mice, Inbred ICR; Myocardium; Phaeophyceae; Time Factors; Xanthophylls

Fucoxanthin, a major carotenoid in edible brown algae, potentially inhibits the proliferation of human prostate cancer cells via apoptosis induction. However, it has been postulated that dietary fucoxanthin is hydrolyzed into fucoxanthinol in the gastrointestinal tract before absorption in the intestine. In the present study, we investigated the further biotransformation of orally administered fucoxanthin and estimated the cytotoxicity of fucoxanthin metabolites on PC-3 human prostate cancer cells. After the oral administration of fucoxanthin in mice, two metabolites, fucoxanthinol and an unknown metabolite, were found in the plasma and liver. The unknown metabolite was isolated from the incubation mixture of fucoxanthinol and mouse liver preparation (10,000 g supernatant of homogenates), and a series of instrumental analyses identified it as amarouciaxanthin A [(3S,5R,6'S)-3,5,6'-trihydroxy-6,7-didehydro-5,6,7',8'-tetrahydro-beta,epsilon-carotene-3',8'-dione]. The conversion of fucoxanthinol into amarouciaxanthin A was predominantly shown in liver microsomes. This dehydrogenation/isomerization of the 5,6-epoxy-3-hydroxy-5,6-dihydro-beta end group of fucoxanthinol into the 6'-hydroxy-3'-oxo-epsilon end group of amarouciaxanthin A required NAD(P)+ as a cofactor, and the optimal pH for the conversion was 9.5 to 10.0. Fucoxanthinol supplemented to culture medium via HepG2 cells was also converted into amarouciaxanthin A. The 50% inhibitory concentrations on the proliferation of PC-3 human prostate cancer cells were 3.0, 2.0, and 4.6 microM for fucoxanthin, fucoxanthinol, and amarouciaxanthin A, respectively. To our knowledge, this is the first report on the enzymatic dehydrogenation of a 3-hydroxyl end group of xanthophylls in mammals.

Topics: Administration, Oral; Animals; Antineoplastic Agents; beta Carotene; Cell Division; Cell Line, Tumor; Humans; In Vitro Techniques; Male; Mice; Microsomes, Liver; Prostatic Neoplasms; Xanthophylls