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KMID : 0613820190290020191
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Journal of Life Science
2019 Volume.29 No. 2 p.191 ~ p.197
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Protective Effects of Quercetin-3-O-glucuronide against 1-methyl-4- phenylpyridinium-induced Neurotoxicity
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Pariyar Ramesh
Bastola Tonking
Seo Jung-Won
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Abstract
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Parkinson’s disease (PD) is a progressive neurodegenerative disease that mainly affects motor system with clinical features such as bradykinesia, rigidity, tremor and abnormal posture. PD is characterized by the death of dopaminergic neurons in the substantia nigra pars compacta, which is associated with accumulation of oxidative stress and dysregulation of intracellular signaling pathway. Quercetin-3-O- glucuronide (Q3GA), a major metabolite of quercetin, has been reported to have neuroprotective effects. In this study, we examined the neuroprotective effect of Q3GA against 1-methyl-4-phenyl pyridinium (MPP+)-induced neurotoxicity of PD and the underlying molecular mechanisms in SH-SY5Y cells. MTT and LDH assay showed that Q3GA significantly decreased MPP+-induced cell death, which is accompanied by a reduction in poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore, it attenuated MPP+-induced intracellular reactive oxygen species (ROS) with the reduction of Bax/ Bcl-2 ratio. Moreover, Q3GA significantly increased the phosphorylation of Akt and cAMP response element binding protein (CREB), but it has no effects on the phosphorylation of extracellular signal?regulated kinase (ERK). Taken together, these results demonstrate that Q3GA significantly attenuates MPP+-induced neurotoxicity through ROS reduction and Akt/CREB signaling pathway in SH-SY5Y cells. Our findings suggest that Q3GA might be one of the potential candidates for the prevention and/or treatment of PD.
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KEYWORD
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Akt, neurotoxicity, Parkinson’s disease, quercetin-3-O-glucuronide, ROS
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