Abstract
Flavonoids represent a diverse group of natural pigments widely distributed in the plant kingdom and are an important component of human diet due to their high content in fruits and vegetables. Since many flavonoids have been shown to be potent inhibitors, substrates, and even inducers of various cytochrome P450 isoforms, there is considerable interest in studying interactions of this class of molecules with the cytochrome P450 enzyme system. In this study, the metabolism of several simple flavanones by rat liver microsomes was investigated and compared. In addition to the expected aromatic hydroxylation products, several novel metabolic pathways were observed including C-ring desaturation to form the corresponding flavones, oxidation of the B-ring to generate an unusual quinol oxidation product, B-ring cleavage with the formation of chromone derivatives, and reduction of carbonyl group to form flavan-4-ol derivatives. The metabolites were characterized and identified primarily by using liquid chromatographytandem mass spectrometry with comparison to authentic standards. Formation of flavones from dietary flavanones might have biological significance since flavones often exhibit pharmacological activities that are different from those of flavanones. However, little is known about the pharmacological activities of the other types of flavonone metabolites.
Footnotes
-
↵1 Abbreviations used are: LC/MS-MS, liquid chromatography tandem mass spectrometry; CID, collision-induced dissociation; HPLC, high-performance liquid chromatography; LC/MS, liquid chromatography-mass spectrometry; FWHM, full width at half-maximum intensity; ee, enantiomeric excess.
-
Supported by Grant P50AT00155 provided to the UIC/National Institutes of Health Center for Botanical Dietary Supplements Research by the Office of Dietary Supplements, the National Institute of General Medical Sciences, the Office for Research on Women's Health, and the National Center for Complementary and Alternative Medicine. The contents are the responsibility of the authors and do not necessarily represent the official views of the sponsors.
- Received August 20, 2003.
- Accepted December 18, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|