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Neuroprotective effect of flavonoids, via up‐regulating Nrf2‐ARE pathway, in MPP + ‐induced PC12 cells, as a model of Parkinson's disease
Author(s) -
Kulkarni Priyanka,
Benzeroual Kenza
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.621.3
Subject(s) - fisetin , oxidative stress , neuroprotection , glutathione , reactive oxygen species , chemistry , antioxidant , programmed cell death , pharmacology , biochemistry , microbiology and biotechnology , quercetin , biology , enzyme , apoptosis
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by intra neuronal proteinaceous cytoplasmic inclusions known as Lewy Bodies. A line of evidence reported formation of dopamine quinones; mitochondrial dysfunction and glutathione loss in SN leads to formation of reactive oxygen species and oxidative stress which ultimately leads to dopaminergic cell death associated with PD. Studies have suggested that flavonoids exhibit a variety of biological activities. However, most interest has been devoted to the antioxidant activity of flavonoids, which is due to their ability to reduce free radical formation and to scavenge free radicals. This study investigated cytoprotective effects of Fisetin and Quercetin against MPP+ induced oxidative stress and neurodegenration in PC12 cells involving NF‐E2‐related factor‐2 (Nrf2) mediated up‐regulation of the antioxidant enzyme NAD(P)H quinone oxidoreducase‐1 (NQO1), Heme Oxygenase‐1(HO‐1) and glutathione. Our results demonstrated that pretreatment with Fisetin and Quercetin not only protected the PC12 cells from MPP+ induced toxicity by increasing cell viability, but also significantly induced the expression of Nrf2‐induced cytoprotective genes NQO‐1, HO‐1 and glutathione. This study emphasized a link between the formations of reactive oxygen species due to mitochondrial dysfunction, depletion of glutathione and dopamine oxidation and also suggests cytoprotective mechanism offered by both Fisetin and Quercetin. This study is supported by research funds of Arnold & Mary Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn NY.