xact direction nor the magnitude of a change in such activity might be precisely predicted around the sole basis with the chemical nature of a flavonoid [98], theoretically, it might be anticipated that nu blocking through methylation, sulfation or glucuronidation, 1 or far more of its redox-active phenolic groups, for D3 Receptor site instance, a single phenolic, catechol or galloyl in ring B, would compromise the flavonoid’s original antioxidant properties [61,99,100]. InAntioxidants 2022, 11,6 ofAntioxidants 2022, 11, x FOR PEER REVIEW6 offact, most studies indicate that when such a variety of Amebae Source metabolites are assayed in vitro for their ROS-scavenging/reducing activity, these have either drastically lost or only marginally retained the antioxidant activity of their precursors, but that in no case have they undergone liver by means of the portal vein, they circulate in systemic blood just about exclusively as O-glucua substantial gain of such activity [74,96,10112]. Basically, comparable in vitro results have ronide, O-sulphate and/or O-methyl ester/ether metabolites (commonly within this order of recently been reported relating to the capacity of some flavonoids’ phase II-conjugation abundance) [69,90]. metabolites to upregulate (by way of an indirect action) the cell’s endogenous antioxidant capacity [80,11315] (Table 1). It should be noted, nevertheless, that in some distinct situations, Table 1. Phenol-compromising reactions. As exemplified for quercetin (Q), the key reactions that impact the redox-active phase I and/or II biotransformation metabolites have already been shown to exert numerous phenol moieties of quercetin are listed. Additionally, the chemical nature of a number of the formed metabolites as well as the effect other, not necessarily the antioxidant properties biological actions that could that the phenol-compromising reactions can have onantioxidant-dependent, on the metabolites are described. substantially contribute to the health-promoting effects of their precursor flavonoids [79,116,117]. Phenol Influence on Metabolites Compromising Reactions Table 1. Phenol-compromising reactions. As exemplified for quercetin (Q), the principle reactions that Antioxidant Potency have an effect on the redox-active phenol moieties of quercetin are general, these metabolites have less of Glycosides (e.g. Q-3-O-glucoside; Q-4-OIn listed. Furthermore, the chemical nature O-Glycosylation a number of the formed metabolites Q-5-O-glucoside the ROS-scavenging potency than their on and also the impact that phenol-compromising reactions can have glucoside; 3,4-O-diglucoside; (in plants) the antioxidant properties in the metabolites are described. and Q-7-O-glucoside) corresponding aglycones The ROS-scavenging potency of OPhenol O-Deglycosylation Quercetin O-deglycosylated in C3, C4 C5 or Effect on Compromising Metabolites deglycosylated metabolites is, in most Antioxidant Potency (in human intestine/colon) C7 Reactions situations, considerably higher These In general, these metabolites have significantly less metabolites have, normally, less O-Glycosylation Glycosides (e.g., Q-3-O-glucoside; Q-4 -O-glucoside; ROS-scavenging potency than their Glucuronides (e.g. Q-3-O- and Q-7-O(in plants) 3,four -O-diglucoside; Q-5-O-glucoside and Q-7-O-glucoside) ROS scavenging/reduction potency but in Biotransformation corresponding aglycones glucuronides) some specific instances are in a position to up(in human intestine/ O-Deglycosylation The ROS-scavenging potency of Sulphates (e.g. Q-3-O-andin C3, C4 , C5 or C7 Q-3′-O-sulphates) (in human Quercetin O-deglycosylated O-deglycosylated meta
