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.