title: Sulfation modulates the cell uptake, antiradical activity and biological effects of flavonoids in vitro: An examination of quercetin, isoquercitrin and taxifolin.
abstract: Quercetin 3'-O-sulfate is one of the main metabolites of the natural flavonoid quercetin in humans. This study was designed to prepare quercetin 3'-O-sulfate (1), isoquercitrin 4'-O-sulfate (2) and taxifolin 4'-O-sulfate (3) by the sulfation of quercetin, isoquercitrin (quercetin 3-O-glucoside) and taxifolin (2,3-dihydroquercetin) using the arylsulfate sulfotransferase from Desulfitobacterium hafniense, and to examine the effect of sulfation on selected biological properties of the flavonoids tested. We found that flavonoid sulfates 1-3 were weaker DPPH radical scavengers than the corresponding nonsulfated flavonoids, and that 1-3, unlike quercetin, did not induce the expression of either heme oxygenase-1 in RAW264.7 cells or cytochrome P450 1A1 in HepG2 cells. In both cell types, the cell uptake of compounds 1-3 was much lower than that of quercetin, but comparable to that of the glycoside isoquercitrin. Moreover, HPLC/MS metabolic profiling in HepG2 cells showed that flavonoid sulfates 1-3 were metabolized to a limited extent compared to the nonsulfated compounds. We conclude that sulfation of the tested flavonoids reduces their antiradical activity, and affects their cell uptake and biological activity in vitro.
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Roubalová
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, Prague 14220, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Purchartová
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, 17 listopadu 12, Olomouc 77146, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Papoušková
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Vacek
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, Prague 14220, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Křen
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Ulrichová
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic. Electronic address: vrbambv@seznam.cz.
authors.forename: Jiří
authors.initials: J
authors.lastname: Vrba
mesh_terms: D000818:Animals; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; C531389:quercetin 3'-sulfate; C016527:isoquercitrin; D011794:Quercetin; C003377:taxifolin; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; D051547:Heme Oxygenase-1
keywords: Antiradical activity; Arylsulfate sulfotransferase; Flavonoids; Gene expression; Metabolism; Sulfate