Methylation protects dietary flavonoids from rapid hepatic metabolism
- 1 May 2006
- journal article
- research article
- Published by Informa UK Limited in Xenobiotica
- Vol. 36 (5), 387-397
- https://doi.org/10.1080/00498250600630636
Abstract
The metabolic stability of two potential cancer chemopreventive flavones, i.e. 5,7-dimethoxyflavone (5,7-DMF) and 3′,4′-dimethoxyflavone (3′,4′-DMF), compared with the non-methylated flavone galangin (3,5,7-trihydroxyflavone), was investigated in human hepatic preparations. Galangin, as expected, was extensively metabolized mainly by glucuronidation in human liver S9 fractions in the presence of appropriate co-factors. In contrast, 5,7-DMF and 3′,4′-DMF were metabolically highly stable with only a small fraction of 3′,4′-DMF undergoing oxidation. Consistent with the S9 fraction results, galangin was almost completely depleted after 2-h incubations in freshly plated hepatocytes. The hepatocytes also showed some metabolism of 3′,4′-DMF, but virtually none of 5,7-DMF. In human liver microsomes, 5,7-DMF was more metabolically stable than 3′,4′-DMF. The observations present a new strategy for examining the metabolic stability of dietary flavonoids and suggest that methylated flavonoids may have a high oral bioavailability compared with their non-methylated forms, which will make them more likely to be useful as cancer chemoprotectants.Keywords
This publication has 23 references indexed in Scilit:
- Lipophilic flavones of Primula veris L. from field cultivation and in vitro culturesPhytochemistry, 2005
- Combination antiangiogenesis therapy with marimastat, captopril and fragmin in patients with advanced cancerBritish Journal of Cancer, 2004
- Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administrationBritish Journal of Cancer, 2004
- IDENTIFICATION OF CYP1A2 AS THE MAIN ISOFORM FOR THE PHASE I HYDROXYLATED METABOLISM OF GENISTEIN AND A PRODRUG CONVERTING ENZYME OF METHYLATED ISOFLAVONESDrug Metabolism and Disposition, 2003
- In vitro Metabolism of Genistein and Tangeretin by Human and Murine Cytochrome P450sBasic & Clinical Pharmacology & Toxicology, 2003
- Resveratrol transport and metabolism by human intestinal Caco-2 cellsJournal of Pharmacy and Pharmacology, 2003
- Quercetin is recovered in human plasma as conjugated derivatives which retain antioxidant propertiesFEBS Letters, 1998
- On the occurrence of methylated and methoxylated flavonoids in Leptospermum scopariumBiochemical Systematics and Ecology, 1998
- Constituents of the Leaves ofPiper caninumPlanta Medica, 1997
- Utility of in vitro drug metabolism data in predicting in vivo metabolic clearanceBiochemical Pharmacology, 1994