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United States Department of Agriculture

Agricultural Research Service

Research Project: BIOACTIVE CONSTITUENTS AND SPECIALTY FOOD FIBERS AS VALUE-ADDED PRODUCTS FROM CITRUS PROCESSING WASTE

Location: Citrus and Other Subtropical Products Research

Title: Pharmacokinetic study of nobiletin and tangeretin in rat serum by high-performance liquid chromatography-electrospray ionization-mass spectrometry

Authors
item Manthey, John
item Cesar, Thais
item Jackson, Erin -
item Talcott, Suzanne -

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 3, 2010
Publication Date: January 6, 2011
Citation: Manthey, J.A., Cesar, T.B., Jackson, E., Mertens-Talcott, S. 2011. Pharmacokinetic study of nobiletin and tangeretin in rat serum by high-performance liquid chromatography-electrospray ionization-mass spectrometry. Journal of Agricultural and Food Chemistry. 59:145-151.

Interpretive Summary: The time courses of the concentrations in blood serum of two important citrus flavonoids with important health benefits were measured in rats. This provided information about the timing of the uptake of these compounds in animals. Metabolites of these compounds were also studied for chemical structures and appearances in the blood serum. Results show that the formulation of these compounds plays an important role in influencing the uptake of these compounds.

Technical Abstract: Nobiletin (NOB) and tangeretin (TAN), two of the main polymethoxylated flavones in citrus, influence a number of key biological pathways in mammalian cells. While 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 original compounds, two metabolites of TAN and 8 metabolites of NOB were detected and monitored. Nearly 10 fold higher absorption of NOB occurred following oral administration 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 Tmax values for NOB and TAN. In most cases the glucuronides occurred at substantially higher levels than those of aglycone metabolites. Low levels of NOB and TAN and their metabolites were detectable in serum even at 24 h post treatment. Eight of the metabolites detected in these studies were isolated and preliminarily analyzed by UV, FTIR, ESI-MS and NMR.

Last Modified: 12/26/2014
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