PI3K/Akt and ERK1/2 Signalling Are Involved in Quercetin-Mediated Neuroprotection against Copper-Induced Injury

Figure 1

(a) Schematic representation of the antioxidative and prooxidative activities of quercetin. Potential Cu(II) chelating sites of quercetin are shown. Cu complexation may result in antioxidative and prooxidative effects. Antioxidative activity is achieved mainly through the direct scavenging activity and Cu complexation which prevents copper from participating in a Fenton-type reaction. In general, the prooxidative activity of quercetin is mainly exhibited in the presence of transition metals such as copper (simplified chemical reactions of the catechol moiety of quercetin are indicated in (b)). In a reaction of quercetin and Cu²⁺, a quercetin-semiquinone radical is formed together with Cu⁺. The superoxide anion further reacts with quercetin yielding a quercetin-semiquinone radical and hydrogen peroxide. In a reaction with hydrogen peroxide that is catalysed by Cu²⁺, quercetin is oxidized to quercetin-semiquinone radicals that further give quercetin-quinone and quercetin. Hence, these reactions result in redox cycling and further ROS formation. Quercetin also readily autoxidizes generating a semiquinone radical and a hydroxyl radical. Furthermore, the prooxidative ability of quercetin is related to its ability to reduce Cu²⁺. The reduced form (Cu⁺) induces prooxidative reactions. In the Fenton reaction with hydrogen peroxide, a hydroxyl radical is formed. Quercetin semiquinones and quinines facilitate the formation of the superoxide anion and reduce GSH levels further leading to a prooxidative environment.

(a)

(b)