Bioorganic & Medicinal Chemistry 2015-09-01

Sulfation modulates the cell uptake, antiradical activity and biological effects of flavonoids in vitro: An examination of quercetin, isoquercitrin and taxifolin.

Lenka Roubalová, Kateřina Purchartová, Barbora Papoušková, Jan Vacek, Vladimír Křen, Jitka Ulrichová, Jiří Vrba

Index: Bioorg. Med. Chem. 23 , 5402-9, (2015)

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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. Copyright © 2015 Elsevier Ltd. All rights reserved.