Pharmacokinetic Study of Nobiletin and Tangeretin in Rat Serum by High-Performance Liquid Chromatography−Electrospray Ionization−Mass Spectrometry

• Published in: Journal of agricultural and food chemistry Vol. 59; no. 1; pp. 145 - 151
• Main Authors: Manthey, John A, Cesar, Thais B, Jackson, Erin, Mertens-Talcott, Susanne
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 12.01.2011
• Subjects: Animals; Bioactive Constituents; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Feeding. Feeding behavior; Flavones - blood; Flavones - pharmacokinetics; Food industries; Fundamental and applied biological sciences. Psychology; Male; Plant Extracts - blood; Plant Extracts - pharmacokinetics; Rats; Rats, Wistar; Spectrometry, Mass, Electrospray Ionization - methods; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Nobiletin; demethylnobiletin; bioavailability; demethyltangeretin; Rutaceae; pharmacokinetics; flavonoids; glucuronides; metabolites; tangeretin; Rat; Metabolite; Rodentia; HPLC chromatography; Bioavailability; Flavonoid; Electrospray; Polyphenol; Vertebrata; Mammalia; Dicotyledones; Angiospermae; Serum; Spermatophyta; Pharmacokinetics; Mass spectrometry
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf1033224

Nobiletin (NOB) and tangeretin (TAN), two of the main polymethoxylated flavones (PMFs) in citrus, influence a number of key biological pathways in mammalian cells. Although the impacts of NOB and TAN on glucose homeostasis and cholesterol regulation have been investigated in human clinical trials, much information is still lacking about the metabolism and oral bioavailability of these compounds in animals. In this study, NOB and TAN were administered to rats by gavage and intraperitoneal (ip) injection, and the blood serum concentrations of these compounds and their main metabolites were monitored by high-performance liquid chromatography−electrospray ionization−mass spectrometry (HPLC-ESI-MS). In addition to the administered compounds, two metabolites of TAN and eight metabolites of NOB were detected and measured over 24 h. With identical oral doses, nearly 10-fold higher absorption of NOB occurred compared to TAN. For both compounds, maximum levels of glucuronidated metabolites occurred in the blood serum at later time points (∼5−8 h) compared to the earlier T max values for NOB and TAN. In most cases the glucuronides occurred at substantially higher concentrations than the aglycone metabolites. Low levels of NOB and TAN and their metabolites were detectable in rat blood serum even at 24 h after treatment.