The neuroprotective effect of fisetin in the MPTP model of Parkinson's disease.
BACKGROUND
Parkinson's disease (PD) is characterized by excessive deposition of neuritic plaques known as Lewy bodies of which α-synuclein is the major contributor to neuronal death. Both oxidative stress and cytokines signaling have been proposed to play an important role in α-synuclein-induced neuronal death in MPTP and PD-related neuronal cell death. Fisetin, a natural polyphenol, possesses antioxidant, anti-inflammatory, and anti-apoptotic properties. However, the molecular neuroprotective mechanisms of fisetin against MPTP-induced cytotoxicity are still unknown.


OBJECTIVE
The present study investigated the inhibitory effect of fisetin on MPTP/MPP+-induced neurotoxicity in PC12 cells.


METHODS
Cells were pretreated with varying concentrations of fisetin prior exposure to MPTP/MPP+. Cell viability and apoptosis were investigated using MTT assay and DNA fragmentation. The expression and release of transcription factor, pro-inflammatory cytokines, and apoptotic mediators were assessed using western blot analysis and ELISA.


RESULTS
Results showed that a pre-treatment with fisetin before exposure to MPTP/MPP+ significantly decreased MPTP/MPP+-induced cytotoxicity and cell death probably by decreasing α-synuclein expression. Mechanisms study showed that fisetin has the potential to inhibit several apoptotic and inflammatory pathways, which play important roles in the initiation and progression of PD.


CONCLUSIONS
Altogether, these observations indicate that fisetin is capable of attenuating α-synuclein levels and promoting neuroprotective effects, meanwhile also present some insights into the potential signaling pathways that are involved. Thus, these findings support the role of natural polyphenols in preventive and/or complementary therapies for neurodegenerative diseases.
Division of Pharmaceutical Sciences, Arnold and Marie Schwartz college of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA.
Mital Y
MY
Patel
Hirenkumar V
HV
Panchal
Othman
O
Ghribi
Kenza E
KE
Benzeroual
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000627:therapeutic use*; D044948:Flavonols; D020267:MPTP Poisoning / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
D005419:Flavonoids; D044948:Flavonols; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; C017875:fisetin