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

摘要

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. (C) 2015 Elsevier Ltd. All rights reserved.