Abstract
α-Cyperone, extracted from Cyperus rotundus, has been reported to inhibit microglia-mediated neuroinflammation. Oxidative stress and apoptosis play crucial roles in the course of Parkinson’s disease (PD). PD is a common neurodegenerative disease characterized by selective death of dopaminergic neurons. This study was designed to investigate the neuroprotective effects of α-cyperone against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in dopaminergic neuronal SH-SY5Y cells. Neurotoxicity was assessed by MTT assay and the measurement of lactic dehydrogenase (LDH) release. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The apoptosis of SH-SY5Y cells was evaluated by annexin-V-FITC staining. The translocation of NF-E2-related factor 2 (Nrf2) was determined by western blot and immunofluorescence staining. Western blot analysis was conducted to determine the expression level of cleaved-caspase-3, the pro-apoptotic factor Bax, and the anti-apoptotic factor, Bcl-2. The results showed that α-cyperone substantially decreased H2O2-induced death, release of LDH, and the production of ROS in SH-SY5Y cells. In addition, we found that α-cyperone attenuated H2O2-induced cellular apoptosis. Moreover, α-cyperone remarkably reduced the expression of cleaved-caspase-3 and Bax, and upregulated Bcl-2. Furthermore, α-cyperone enhanced the nuclear translocation of Nrf2. Pretreatment with brusatol (BT, an Nrf2 inhibitor) attenuated α-cyperone-mediated suppression of ROS, cleaved-caspase-3, and Bax, as well as α-cyperone-induced Bcl-2 upregulation in H2O2-treated SH-SY5Y cells. α-cyperone neuroprotection required Nrf2 activation. In conclusion, α-cyperone attenuated H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells via the activation of Nrf2, suggesting the potential of this compound in the prevention and treatment of PD.
Highlights
Parkinson’s disease (PD) is the second most common ageassociated neurodegenerative disorder, affecting about 2% of subjects older than 60 years and more than 5 million people worldwide (Olanow et al, 2009)
We reported the neuroprotective effect of a-cyperone in an in vitro model of PD based on the exposure of SH-SY5Y human neuroblastoma cells to H2O2
Our results revealed that a-cyperone reduced the excessive production of reactive oxygen species (ROS), and attenuated mitochondrial dysfunction and cellular apoptosis in H2O2-induced SH-SY5Y cells
Summary
Parkinson’s disease (PD) is the second most common ageassociated neurodegenerative disorder, affecting about 2% of subjects older than 60 years and more than 5 million people worldwide (Olanow et al, 2009). It has been demonstrated that oxidative stress and mitochondrial dysfunction can cause neuronal damage and degeneration in PD pathogenesis (Henchcliffe and Beal, 2008; Hauser and Hastings, 2013; Subramaniam and Chesselet, 2013). Inhibition of these events is a potential strategy to protect dopaminergic neurons
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