Naringenin Protects against 1‑Methyl‑4‑Phenylpyridinium‑ Induced Neuroinflammation and Resulting Reactive Oxygen Species Production in SH‑SY5Y Cell Line: An In vitro Model of Parkinson’s Disease

ABSTRACT

Background: Parkinson’s disease is a progressive neurodegenerative disorder which affects 1% of the population worldwide. It is well known that 1‑methyl‑4‑phenylpyridinium (MPP+) selectively and potentially inhibit Complex I of the mitochondrial electron transport chain. This inactivation leads to the generation of reactive oxygen species (ROS), which in turn damage neurons. In addition, neuroinflammation plays a major role in neurodegeneration processes. Objective: In the present study, the effect of naringenin (NGN), on MPP+‑induced neuroinflammation and ROS generation in SH‑SY5Y cells were investigated. Materials and Methods: Cells were pretreated with (0.1% dimethyl sulfoxide) or NGN (25, 50, and 100 µm/mL) for 24 h, and then induced with 1 mM MPP+ for 15 min. Following overnight incubation, cells were harvested for ROS staining, gene expression of apoptotic markers such as B‑cell lymphoma‑2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax), inflammatory markers such as tumor necrosis factor‑alpha (TNF‑α), and nuclear factor‑κB (NF‑κB) and protein expression of neuronal markers such as dopamine transporter (DAT), tyrosine hydroxylase (TH), and α‑synuclein (SYN). Results: In this study, NGN exhibited oxidative protection by decreasing ROS generation which is evidenced through significant regulation of oxidative stress markers. Likewise, NGN decreased TNF‑α, Bax, and NF‑κB and increased Bcl‑2 gene expressions in MPP+‑induced SH‑SY5Y cells compared to normal SH‑SY5Y cells. Further, NGN significantly and dose‑dependently decreased SYN and increased DAT and TH levels in MPP+‑induced SH‑SY5Y cells in comparison to the normal cells. Conclusion: The results obtained from the present study revealed that NGN has the potential to encounter MPP+‑induced dopaminergic degeneration through regulating ROS generation and neuroinflammation.

KEYWORDS

• 1‑methyl‑4‑phenylpyridinium
• naringenin
• neuroinflammation
• Parkinson’s disease
• reactive oxygen species
• SH‑SY5Y

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• DOI10.4103/pm.pm_23_18Copy

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