Influence of quercetin on oxidative stress biomarkers and neurotoxic enzyme dysregulation in in vitro and ex vivo studies

Abstract

Oxidative stress and impaired neurotoxic enzymes have been implicated in the etiology of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, that are characterized by cognitive and motor deficits. Quercetin is a natural flavonoid found in a wide range of plants and exhibits strong antioxidant and protective effects against the neuronal system. Its anti-oxidative and neurotoxic enzymes inhibitory effects were studied and compared with those of ascorbic acid and donepezil in this study. Antioxidants assessment (1'1-diphenyl-2-picryl hydrazine (DPPH) radical, Ferric Reducing Antioxidant Power (FRAP), Fe² chelation, hydroxyl radical (OH•), nitric oxide (NO•), and lipid peroxidation), acetylcholinesterase, and monoamine oxidase inhibitors were evaluated according to established methods.The results showed that quercetin scavenged DPPH (EC50 = 0.485 mM) and nitric oxide radicals (EC₅₀ = 0.0260 mM) and chelated Fe²⁺ ions (EC₅₀ = 0.032 mM) more efficiently compared to ascorbic acid (EC50 = 1.485 mM, 0.0464 mM, and 0.037 mM, respectively). It was also found to have greater FRAP (0.69 mg AAE/g) than ascorbic acid (0.63 mg AAE/g). Although ascorbic acid was more potent in hydroxyl radical scavenging (EC50 = 0.0104 mM), quercetin was more effective in inhibiting FeSO4-induced lipid peroxidation (IC50 = 0.0138 mM vs. 0.0233 mM). Quercetinwas as effective in acetylcholinesterase inhibition (IC50 = 0.0131 mM) as donepezil and ascorbic acid (both IC50 = 0.0126 mM), but weaker against monoamine oxidase (IC50 = 0.072 mM) than donepezil (0.056 mM) and ascorbic acid (0.052 mM). These observations indicate that quercetin, by modulating both oxidative stress and dysfunctional cholinergic and monoaminergic enzymes, could have a multi-targeted action in the prevention of neurodegenerative events.