Abstract

Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson’s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH) release when exposed to hydrogen peroxide (H2O2). The significantly-alleviated intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and lipoperoxidation of the cell membrane of PC-12 cells induced by H2O2 were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in PC-12 cells exposed to H2O2 were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress.

Highlights

  • The balance between oxidant and anti-oxidant intracellular systems is very important for cell function

  • Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress

  • The increasing levels of endogenous antioxidant enzymes, in turn, catalyzed the detoxification of superoxide radicals to less toxic molecules, led to the attenuation of oxidative stress, and is directly correlated with increased cellular antioxidant capabilities [36,37]. These results suggest that quercetin could activate the native antioxidant mechanisms in the PC-12 cells during the pretreatment phase, which was able to protect these cells from undergoing H2 O2 -induced oxidative damage

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Summary

Introduction

The balance between oxidant and anti-oxidant intracellular systems is very important for cell function. Disruption in the antioxidant redox system results in excessive production and progressive accumulation of reactive oxygen species (ROS), such as super oxygen ions, H2 O2 and hydroxy free radicals, etc. ROS produced during normal metabolism of oxygen plays an important role in cell signaling [1]. Excessive ROS production during various pathological conditions is a potent inducer of apoptosis, which causes oxidative damage to various biological macromolecules, including. DNA, proteins in plasma, and lipids in cell membranes, thereby disrupting cellular function and initiating subsequent cell death via necrosis or apoptosis [2,3,4]. Many studies show that oxidative damage by ROS is widely implicated in neurodegenerative disorders. Alleviating or preventing oxidative damage by ROS should be a potential therapeutic target for neurodegenerative diseases

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