Protective Mechanisms of Quercetin Against Myocardial Ischemia Reperfusion Injury

Abstract

Quercetin has attracted more attention in recent years due to its protective role against ischemia/reperfusion injury. Quercetin can alleviate oxidative stress injury through the inhibition of NADPH oxidase and xanthine oxidase, blockage of the Fenton reaction, and scavenging of reactive oxygen species. Quercetin can also exert anti-inflammatory and anti-apoptotic effects by reducing the response to inflammatory factors and inhibiting cell apoptosis. Moreover, it can induce vasodilation effects through the inhibition of endothelin-1 receptors, the enhancement of NO stimulation and the activation of the large-conductance calcium-activated potassium channels. Finally, Quercetin can also antagonize the calcium overload. These multifaceted activities of Quercetin make it a potential therapeutic alternative for the treatment of ischemia/reperfusion injury.

Keywords: calcium overload; ischemia/reperfusion injury; oxidative stress; quercetin; vasodilatation.

FIGURE 1

The structure of Quercetin. The flavonoid Quercetin is a 3,30,40,5,7-pentahydroxyflavone with the chemical formula C₁₅H₁₀O₇, a member of flavonoids. Quercetin has a strong antioxidant property due to the presence of five hydroxyl groups in the structure and the pyrocatechol-kind of benzene ring makes it a good scavenger of free radicals.

FIGURE 2

The injury mechanism in ischemia/reperfusion period. During the ischemic period, anaerobic metabolism, and anaerobic glycolysis are promoted, leading to a decrease in oxygen tension, ATP generation and the decline of pH. The lack of ATP leads to the disorder of ion exchanges. The decline of pH provides an acidic environment for Fenton reaction. Blood restoration disturbs the balance of oxidation/anti-oxidation system and quick sodium-calcium exchange. The quick sodium-calcium exchange causes the Ca²⁺ accumulation and impairs the mitochondria. Furthermore, the reperfusion leads to a burst of ROS, mainly deriving from NADPH oxidase, xanthine oxidase and Fenton reaction.

FIGURE 3

Quercetin’s prohibitive effective to NADPH oxidase. NADPH oxidase plays a vital role in generating ROS. On the setting of NADPH oxidase, NADPH transfers one electron to O₂, then forms NADP⁺ and O₂^⋅–, and O₂^⋅– will transfer into H₂O₂ rapidly. However, Que can decrease the expression of Nox2 and ameliorate the oxidative stress.

FIGURE 4

Quercetin’s prohibitive effective to xanthine oxidase. Xanthine oxidase is a homodimer, and it is also a major source of ROS. Xanthine oxidase catalyzes hypoxanthine/xanthine into xanthine/uric acid, and xanthine oxidase itself turns into reduced form. Afterward, xanthine oxidase (reduced form) catalyzes O₂ into O₂^⋅– and H₂O₂. Quercetin can inhibit the O₂^⋅– generation induced by xanthine oxidase, and this effect is associated with the reduced form of xanthine oxidase by a ping-pong mechanism.