Protective Effects of Resveratrol and Quercetin Against MPP+ -Induced Oxidative Stress Act by Modulating Markers of Apoptotic Death in Dopaminergic Neurons

Bournival, Julie; Quessy, Patrik; Martinoli, Maria-Grazia

doi:10.1007/s10571-009-9411-5

Cited by 164 publications

(136 citation statements)

References 94 publications

(127 reference statements)

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“…Although quercetin and structurally related flavonoids have been shown to have a neuroprotective capacity in various in vitro and in vivo experimental models (13)(14)(15)(16), the neuroprotective (17). Nevertheless, quercetin did not protect substantia nigra neurons from an oxidative insult in vivo, probably due to its inability to cross the blood-brain barrier (BBB) under in vivo conditions (18).…”

Section: Introductionmentioning

confidence: 99%

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

Lee

2011

Int J Mol Med

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Abstract.Flavonoids have been reported to be potent antioxidants and beneficial in the treatment of oxidative stress-related diseases. Quercetin, a major flavonoid naturally occurring in plants, deserves attention because of its beneficial effects observed in various in vitro and in vivo neural damage models; however, the actions of quercetin are paradoxical. In an effort to confirm the neuroprotective effect of quercetin and to elucidate its mechanism of action, the neuroprotective effects of quercetin in PC12 cells and in zebrafish models were investigated. In this study, the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA), was used to induce neural damage in PC12 cells and zebrafish models. Pretreatment with quercetin offered neuroprotection against 6-OHDA-induced PC12 cell death. Moreover, quercetin could prevent 6-OHDA-induced PC12 cell apoptosis and 6-OHDA-stimulated dopaminergic neuron loss in zebrafish. Interestingly, quercetin was able to protect, but not rescue the dopaminergic neuron damage when zebrafish were treated with quercetin at different maturation stages of the blood brain barrier. A mechanistic study showed that quercetin could inhibit NO over-production and iNOS over-expression in PC12 cells and could down-regulate the over-expression of pro-inflammatory genes (e.g. IL-1ß, TNF-· and COX-2) in zebrafish, suggesting that these genes play a role in the neuroprotective effect of quercetin. The objective of this study was to provide a scientific rationale for the clinical use of quercetin, leading to its development as an effective therapeutic agent for the treatment of Parkinson's disease.

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Section: Introductionmentioning

confidence: 99%

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

Lee

2011

Int J Mol Med

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“…The results appear to be due to the anti-oxidant effects of flavonoid compounds in C. tschonoskii EtOH extract and are also directly supported by previous studies which have shown both cytoprotective and ROS scavenging activities of C. tschonoskii extract against H 2 O 2 induced oxidative stress (Zhang et al, 2007). Moreover, quercetin, a flavonoid component of C. tschonoskii extract, has been reported to protect dopamine neurons from oxidative insults and apoptosis (Mercer et al, 2005;Bournival et al, 2009). On the other hand, catechins of green tea have been also shown to inhibit 6-OHDA-induced apoptosis in PC12 cells (Nie et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Carpinus tschonoskii MAX on 6-Hydroxydopamine-Induced Death of PC12 Cells

Kim¹,

Kim

Kang³

et al. 2010

Biomolecules and Therapeutics

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-The present study investigated the neuroprotective effect of Carpinus tschonoskii MAX and its intracellular protective mechanism on 6-hydroxydopamine (6-OHDA)-induced oxidative damage in PC12 cells. We found that pretreatment of PC12 cells with C. tschonoskii extract significantly inhibited the cell death induced by 6-OHDA in a dose dependent manner. C. tschonoskii extract decreased 6-OHDA-induced apoptotic events such as chromatin condensation, DNA fragmentation, the decrease of Bcl-2/Bax ratio, caspase-3 activation and PARP cleavage. C. tschonoskii extract also reduced generation of 6-OHDA-induced reactive oxygen species and nitric oxide. Furthermore, C. tschonoskii extract up-regulated the myocyte enhancer factor 2 D (MEF2D), a critical transcription factor for neuronal survival, and Akt activity, whereas it inhibited the activity of ERK1/2 and JNK. The results suggest that C. tschonoskii extract decreases 6-OHDA-induced oxidative stress and could prevent PC12 cell apoptosis induced by 6-OHDA via the up-regulation of MEF2D and Akt activity, and thus may have application in developing therapeutic agents for Parkinson's disease.

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“…Administration of resveratrol or quercetin before MPTP treatment reduced apoptotic cell death and modulated expression of Bax and Bcl-2 in PC12 cultures (Bournival et al, 2009(Bournival et al, , 2012. Resveratrol has elicited neuroprotective effects by preventing behavioral, biochemical, and histopathological changes that occur in PD animal models Khan et al, 2010).…”

Section: Alcoholmentioning

confidence: 98%

Splice Variant Biomarkers for Parkinson's Disease

Potashkin¹

2014

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATEMay PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) PERFORMING ORGANIZATION REPORT NUMBERRosalind Franklin U. Medicine & Science 3333 Green Bay Rd. North Chicago, IL 60064-3037 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTRecently we identified splice variants in whole blood than can distinguish early stage Parkinson's disease (PD) patients from healthy and neurodegenerative controls. The proposed studies will test the hypothesis that the biomarkers will be useful for identifying individuals at risk for PD and for identifying signaling pathways that are disrupted in PD. We are testing the expression of the biomarkers in RNA prepared from whole blood of hyposmic participants in the Parkinson's Associated Risk Study (PARS) (Technical Objective 1.0). In order to establish a model for testing the function of the biomarkers, we are determining whether their expression is altered in human olfactory neurosphere-derived (hONS) cells derived from idiopathic PD patients and healthy controls (Technical Objective 2.0). To determine the signaling pathways affected in PD and identify additional biomarkers, we are using network analysis (Technical Objective 3.0). During year 1, RNA and cDNA was prepared from PARS samples from Year 0 (baseline) and Year 2. Quantitative polymerase chain reactions were initiated for two of the biomarkers (APP, HNF4α). Expression of the biomarkers was tested in hONS. We also developed network approaches to reveal the common molecular pathways involved with PD and type 2 diabetes (T2DM). Using these networks, we identified APP, HNF4A and SOD2 mRNAs as blood biomarkers predictive of early stage PD. In addition, we determined that HNF4A mRNA may be a progression marker in blood for PD. SUBJECT TERMSParkinson's disease, biomarkers, neurodegeneration, network and pathway analysis 12-15Santiago 16-23Sei...

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Protective Effects of Resveratrol and Quercetin Against MPP+ -Induced Oxidative Stress Act by Modulating Markers of Apoptotic Death in Dopaminergic Neurons

Cited by 164 publications

References 94 publications

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

Neuroprotective Effects of Carpinus tschonoskii MAX on 6-Hydroxydopamine-Induced Death of PC12 Cells

Splice Variant Biomarkers for Parkinson's Disease

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