Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Inhibitory Effect of Quercetin on Oxidative Endogen Enzyme: A Focus on Putative Binding Modes

Version 1 : Received: 19 May 2023 / Approved: 22 May 2023 / Online: 22 May 2023 (10:12:36 CEST)

How to cite: Olla, S.; Siguri, C.; Fais, A.; Era, B.; Fantini, M.C.; Di Petrillo, A. Inhibitory Effect of Quercetin on Oxidative Endogen Enzyme: A Focus on Putative Binding Modes. Preprints 2023, 2023051496. https://doi.org/10.20944/preprints202305.1496.v1 Olla, S.; Siguri, C.; Fais, A.; Era, B.; Fantini, M.C.; Di Petrillo, A. Inhibitory Effect of Quercetin on Oxidative Endogen Enzyme: A Focus on Putative Binding Modes. Preprints 2023, 2023051496. https://doi.org/10.20944/preprints202305.1496.v1

Abstract

Oxidative stress is defined as an imbalance between the production of free radicals and reactive oxygen species (ROS) and the ability of the body to neutralize them by antioxidant defense systems. Cells produce ROS as a control of physiological processes, but increasing ROS becomes pathological leading to non-specific and irreversible damage to biological molecules, such as DNA, lipid, and protein. Endogenous ROS are mainly produced by mitochondria during both physiological and pathological conditions, and enzymes, such as nicotinamide adenine dinucleotide phosphate oxidase (NOX), xanthine oxidase (XO), lipoxygenase (LOX), myeloperoxidase (MPO) and monoamine oxidase (MAO). To neutralize ROS, the body employs enzymatic and non-enzymatic defense systems. The dietary intake of bioactive phenols, such as quercetin (Que), is a non-enzymatic system that can quench ROS and protect from pro-oxidative damage. In this review, we evaluate the ability of Que to target endogenous oxidant enzymes involved in ROS production and explore the mechanisms of action underlying its antioxidant properties. Que not only acts as a free radical scavenger by donating electrons through the negative charges in its phenolic and ketone groups, but it can effectively inhibit the activity of several endogenous oxidative enzymes, binding them with high affinity and specificity. Among all targets, Que showed the best results in molecular docking simulations with XO, followed by MAO-A, 5-LOX, NOX, and MPO. Taken together, these findings highlight the potential of Que as a natural antioxidant therapy for oxidative stress-related diseases.

Keywords

Quercetin; xanthine oxidase; myeloperoxidase; nicotinamide adenine dinucleotide phosphate oxidase; lipoxygenase; monoamine oxidase; docking

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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