title: Inhibition of hydroxycinnamic acid sulfation by flavonoids and their conjugated metabolites.
abstract: Hydroxycinnamic acids and flavonoids are dietary phenolic antioxidants that are abundant in our diet. Hydroxycinnamic acids are highly sulfated in vivo, and sulfotransferases (SULTs), in particular SULT1A1, play a major role in their metabolism. Flavonoids are potent inhibitors of human SULTs. In this study, the potential metabolic interaction between dietary hydroxycinnamic acids and flavonoids was investigated. Flavonoids, such as luteolin, quercetin, daidzein, and genistein, are identified as potent inhibitors of hydroxycinnamic acid sulfation in human liver S9 homogenate with IC50 values <1 µM. The inhibitory activity was less potent in the human intestinal S9 homogenate. We also demonstrate that quercetin conjugates found in vivo (quercetin-3-O-glucuronide, quercetin-7-O-glucuronide, and quercetin-3'-O-sulfate) moderately inhibited the sulfation of hydroxycinnamic acids in human liver S9. In an intact cellular system, human HepG2 cells, caffeic acid and ferulic acid sulfation was inhibited by luteolin and quercetin (IC50 : 1.6-3.9 µM). Quercetin-3'-O-sulfate weakly inhibited sulfation. Quercetin glucuronides, limited by their low cellular uptake, were ineffective. These data suggest that the inhibition of SULTs by flavonoids and in vivo flavonoid conjugates may modify the bioavailability of dietary hydroxycinnamic acids by suppressing their conversion to sulfated metabolites.
authors.affiliation: School of Food Science and Nutrition, University of Leeds, UK.
authors.forename: Chi Chun
authors.initials: CC
authors.lastname: Wong
authors.forename: Gary
authors.initials: G
authors.lastname: Williamson
mesh_terms: D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002109:Caffeic Acids / Q000378:metabolism; D003373:Coumaric Acids / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007422:Intestines / Q000201:enzymology; D007529:Isoflavones / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D047311:Luteolin / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*
chemical_list: D002109:Caffeic Acids; D003373:Coumaric Acids; D007529:Isoflavones; C004742:daidzein; D011794:Quercetin; C004999:ferulic acid; D019833:Genistein; D015239:Arylsulfotransferase; D047311:Luteolin
keywords: flavonoid conjugates; flavonoids; hydroxycinnamic acids; sulfation