Abstract
Sulfated quercetin derivatives are important authentic standards for metabolic studies. Quercetin-3′-O-sulfate, quercetin-4′-O-sulfate, and quercetin-3-O-sulfate as well as quercetin-di-O-sulfate mixture (quercetin-7,3′-di-O-sulfate, quercetin-7,4′-di-O-sulfate, and quercetin-3′,4′-di-O-sulfate) were synthetized by arylsulfotransferase from Desulfitobacterium hafniense. Purified monosulfates and disulfates were fully characterized using MS and NMR and tested for their 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) and N,N-dimethyl-p-phenylenediamine (DMPD) radical scavenging, Folin-Ciocalteau reduction (FCR), ferric reducing antioxidant power (FRAP), and anti-lipoperoxidant activities in rat liver microsomes damaged by tert-butylhydroperoxide. Although, as expected, the sulfated metabolites were usually less active than quercetin, they remained still effective antiradical and reducing agents. Quercetin-3′-O-sulfate was more efficient than quercetin-4′-O-sulfate in DPPH and FCR assays. In contrast, quercetin-4′-O-sulfate was the best ferric reductant and lipoperoxidation inhibitor. The capacity to scavenge ABTS+• and DMPD was comparable for all substances, except for disulfates, which were the most efficient. Quantum calculations and molecular dynamics simulations on membrane models supported rationalization of free radical scavenging and lipid peroxidation inhibition. These results clearly showed that individual metabolites of food bioactives can markedly differ in their biological activity. Therefore, a systematic and thorough investigation of all bioavailable metabolites with respect to native compounds is needed when evaluating food health benefits.
Highlights
Quercetin is a prominent food bioactive flavonol whose daily intake has considerably increased due to its use as food supplements [1] and mainly due to the “eat five fruits and vegetables a day” international recommendation
To extend our knowledge about the different quercetin sulfates that can be produced by AST from D. hafniense using p-nitrophenylsulfate (p-NPS) as sulfate donor, the time course of synthesis of all detectable soluble sulfated products was investigated
Reaction times longer than ca 5 h were associated with considerable formation of polymeric non-soluble byproducts, and the hydrolysis of the sulfates, which afforded the starting material quercetin (Figure 1 and Figure S1)
Summary
Quercetin is a prominent food bioactive flavonol whose daily intake has considerably increased due to its use as food supplements [1] and mainly due to the “eat five fruits and vegetables a day” international recommendation. Quercetin aglycone suffers from low water solubility, poor bioavailability, and instability [2]. Quercetin pharmacokinetics and metabolism have been extensively studied and it was found that after deglycosylation of respective glycosides in the small intestine it is preferentially sulfated, glucuronidated or O-methylated by Phase II biotransformation enzymes [3,4]. In most of the studies on bioavailability, the level of quercetin in biological samples (mostly blood plasma and/or urine) was measured as the sum of free and conjugated (after conjugate hydrolysis by gut enzymes from Helix pomatia) aglycones). Specific determination of conjugates is typically accomplished using HPLC/MS [2]. The following quercetin conjugates were identified in human plasma: quercetin-3-O-glucuronide, quercetin glucuronide sulfate (without determination of the conjugation positions), isorhamnetin-3-O-glucuronide, quercetin-3 -O-sulfate and isorhamnetin [5]. The identification of the exact structures of these metabolites (i.e., position of conjugation) requires authentic and well-characterized standards
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
