er was evidenced not only by testing the antioxidant activity of Q-BZF, chromatographically isolated from Qox, but additionally, just after comparing the activity of Qox with that of a Qox preparation from which Q-BZF was experimentally removed by chemical subtraction. Remarkably, the antioxidant protection afforded by the isolated Q-BZF was seen at a 50 nM concentration, namely at a concentration 200-fold decrease than that of quercetin [57]. For the finest of our knowledge, there are no reports within the literature of any flavonoid or flavonoid-derived molecule ALDH3 Purity & Documentation capable of acting as antioxidant within cells at such incredibly low concentrations. The possibility that such a distinction in intracellular antioxidant potency becoming explained with regards to a 200-fold difference in ROS-scavenging capacity is extremely low given that; along with lacking the double bond present in ring C of quercetin, Q-BZF doesn’t differ from quercetin in terms of the quantity and position of their phenolic hydroxyl groups. H3 Receptor Source Contemplating the really low concentration of Q-BZF needed to afford protection against the oxidative and lytic damage induced by hydrogen peroxide or by indomethacin to Hs68 and Caco-2 cells, Fuentes et al. [57] proposed that such effects of Q-BZF may be exerted by means of Nrf2 activation. Relating to the potential from the Q-BZF molecule to activate Nrf2, a number of chalcones have already been shown to act as potent Nrf2 activators [219,220]. The electrophilic carbonyl groups of chalcones, such as these inside the two,three,4-chalcan-trione intermediate of Q-BZF formation (Figure 2), may very well be able to oxidatively interact with the cysteinyl residues present in Keap1, the regulatory sensor of Nrf2. Interestingly, an upregulation of this pathway has already been established for quercetin [14345]. Considering the truth that the concentration of Q-BZF needed to afford antioxidant protection is at the least 200-fold reduce than that of quercetin, and that Q-BZF may be generated during the interaction among quercetin and ROS [135,208], 1 might speculate that if such a reaction took location inside ROS-exposed cells, only 1 out of 200 hundred molecules of quercetin would be needed to become converted into Q-BZF to account for the protection afforded by this flavonoid–though the occurrence from the latter reaction in mammalian cells remains to become established.Antioxidants 2022, 11,14 ofInterestingly, as well as quercetin, a number of other structurally connected flavonoids have been reported to undergo chemical and/or electrochemical oxidation that results in the formation of metabolites with structures comparable to that of Q-BZF. Examples of the latter flavonoids are kaempferol [203,221], morin and myricetin [221], fisetin [22124], rhamnazin [225] and rhamnetin [226] (Figure three). The formation from the 2-(benzoyl)-2-hydroxy-3(2H)benzofuranone derivatives (BZF) corresponding to each of the six previously talked about flavonoids demands that a quinone methide intermediate be formed, follows a pathway comparable to that of your Q-BZF (Figure 2), and results in the formation of a series of BZF Antioxidants 2022, 11, x FOR PEER Critique 15 of 29 exactly where only the C-ring of the parent flavonoid is changed [203,225]. From a structural requirement perspective, the formation of such BZF is limited to flavonols and seems to call for, as well as a hydroxy substituent in C3, a double bond in the C2 3 plus a carbonyl group in C4 C4 (i.e., standard attributes of of any flavonol), flavonol possesses at and also a carbonyl group in(i.e.,
