Affiliations: Division of Food Science and Biotechnology, Graduate
School of Agriculture, Kyoto University, Kyoto 606-8502, Japan | Department of Biotechnological Science, Faculty of
Biology-Oriented Science and Technology, Kinki University, Iwade-Uchita,
Wakayama 649-6493, Japan | The Research and Development Division, Wakayama
Agricultural Processing Research Corporation, 398, Tsukatsuki Momoyama-Cho,
Nagagun, Wakayama 649-6112, Japan | Faculty of Education, Wakayama University, 930,
Sakaedani, Wakayama 640-8510, Japan
Note: [] Address for correspondence: Akira Murakami, Division of Food
Science and Biotechnology, Graduate School of Agriculture, Kyoto University,
Kyoto 606-8502, Japan. Tel.: +81 75 753 6282; Fax: +81 75 753 6284; E-mail:
cancer@kais.kyoto-u.ac.jp
Abstract: 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 μmol/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.
