The Nrf2/HO-1 Axis as Targets for Flavanones: Neuroprotection by Pinocembrin, Naringenin, and Eriodictyol

Flavanones are a group of flavonoids that derive from their immediate chalcone precursors through the action of chalcone isomerase enzymes. The Aromatic A and B rings, C4-keto group, and the 15-carbon flavonoid skeleton are all evident in flavanones, but a notable absence of C2-C3 double bond and a lack of oxygenation at C-3 position of the C-ring makes them distinctively different from other groups such as flavonols (e.g., quercetin). On the basis of oxygenation level in the B ring, flavanones can vary from each other as exemplified by pinocembrin (no oxygenation), naringenin (4′-hydroxyl), or eriodictyol (3′,4′-dihydroxyl substitution). These groups are generally weaker free radical scavengers as compared to quercetin and derivatives though eriodictyol has a better free radical scavenging profile within the group due to the presence of the catechol functional moiety. In this communication, their antioxidant potential through the induction of antioxidant defenses is scrutinized. These compounds as exemplified by pinocembrin could induce the nuclear factor erythroid 2-related factor 2- (Nrf2-) heme oxygenase-1 (HO-1) axis leading to amelioration of oxidative stress in cellular and animal models. Their neuroprotective effect through such mechanism is discussed.