xact direction nor the magnitude of a alter in such activity is often precisely predicted around the sole basis from the chemical nature of a flavonoid [98], theoretically, it can be anticipated that nu blocking via methylation, sulfation or glucuronidation, 1 or a lot more of its redox-active phenolic groups, for example, a LIMK2 list single phenolic, catechol or galloyl in ring B, would compromise the flavonoid’s original antioxidant properties [61,99,100]. InAntioxidants 2022, 11,six ofAntioxidants 2022, 11, x FOR PEER REVIEW6 offact, most studies indicate that when such a type of metabolites are assayed in vitro for their ROS-scavenging/reducing activity, these have either significantly lost or only marginally retained the antioxidant activity of their precursors, but that in no case have they undergone liver via the portal vein, they circulate in systemic blood practically exclusively as O-glucua substantial achieve of such activity [74,96,10112]. Primarily, comparable in vitro final results have ronide, O-sulphate and/or O-methyl ester/ether metabolites (commonly within this order of recently been reported regarding 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 needs to be noted, on the other hand, that in some certain instances, Table 1. Phenol-compromising reactions. As exemplified for quercetin (Q), the principle reactions that CYP1 Storage & Stability influence the redox-active phase I and/or II biotransformation metabolites happen to be shown to exert many phenol moieties of quercetin are listed. In addition, the chemical nature of some of the formed metabolites and also the effect other, not necessarily the antioxidant properties biological actions that could that the phenol-compromising reactions can have onantioxidant-dependent, of the metabolites are described. substantially contribute towards the health-promoting effects of their precursor flavonoids [79,116,117]. Phenol Impact on Metabolites Compromising Reactions Table 1. Phenol-compromising reactions. As exemplified for quercetin (Q), the primary reactions that Antioxidant Potency have an effect on the redox-active phenol moieties of quercetin are general, these metabolites have much less of Glycosides (e.g. Q-3-O-glucoside; Q-4-OIn listed. In addition, the chemical nature O-Glycosylation a few of the formed metabolites Q-5-O-glucoside the ROS-scavenging potency than their on plus the influence that phenol-compromising reactions can have glucoside; three,4-O-diglucoside; (in plants) the antioxidant properties of 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 instances, considerably greater These In general, these metabolites have much less metabolites have, generally, much 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) three,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