xact path nor the magnitude of a transform in such activity is usually precisely predicted on the sole basis from the chemical nature of a flavonoid [98], theoretically, it could be expected that nu blocking through methylation, sulfation or glucuronidation, one particular or additional of its redox-active phenolic groups, for example, 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 sort 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 virtually exclusively as O-glucua substantial obtain of such activity [74,96,10112]. Essentially, comparable in vitro benefits have ronide, O-sulphate and/or O-methyl ester/ether metabolites (commonly in this order of lately been reported with regards to the capacity of some flavonoids’ phase II-conjugation abundance) [69,90]. metabolites to upregulate (via an indirect action) the cell’s endogenous antioxidant capacity [80,11315] (Table 1). It really should be noted, nevertheless, that in some distinct cases, Table 1. Phenol-compromising reactions. As exemplified for quercetin (Q), the key reactions that affect the redox-active phase I and/or II biotransformation metabolites have been shown to exert numerous phenol moieties of quercetin are listed. Furthermore, the chemical nature of some of the formed metabolites along with the influence 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 towards the health-promoting effects of their precursor flavonoids [79,116,117]. Phenol Effect on Metabolites Compromising Reactions Table 1. Phenol-compromising reactions. As exemplified for quercetin (Q), the main reactions that Antioxidant Potency impact the redox-active phenol moieties of quercetin are common, these metabolites have much less of Glycosides (e.g. Q-3-O-glucoside; Q-4-OIn listed. Moreover, the chemical nature O-Glycosylation some of the formed metabolites Q-5-O-glucoside the ROS-HSV Formulation scavenging potency than their on and the effect that phenol-compromising reactions can have glucoside; three,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 Influence on Compromising Metabolites deglycosylated metabolites is, in most Antioxidant Potency (in human intestine/colon) C7 Reactions situations, considerably larger These Generally, these metabolites have less metabolites have, generally, 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) 3,4 -O-diglucoside; Q-5-O-glucoside and Q-7-O-glucoside) ROS scavenging/reduction potency but in Biotransformation corresponding aglycones glucuronides) some specific HSP105 manufacturer instances are capable 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
