Naringenin Inhibit the Hydrogen Peroxide-Induced SH-SY5Y Cells Injury Through Nrf2/HO-1 Pathway
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Naringenin (NGN), a flavonoid, abundantly present in citrus fruits, has been established as a neuroprotective agent. However, the precise protective mechanisms remain worthy of further investigation. The present study was designed to explore the protective effects of NGN against hydrogen peroxide (H2O2)-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and the possible mechanisms involved. Exposure of cells to 400 μM H2O2 for 2 h caused viability loss, apoptotic increase, and reactive oxygen species (ROS) increase, pre-treatment with NGN for 12 h significantly reduced the viability loss, apoptotic rate, and attenuated H2O2-mediated ROS production. In addition, NGN inhibited H2O2-induced mitochondrial dysfunctions, including lowered membrane potential, decreased Bcl-2/Bax ratio, cytochrome c release, and the cleavage of caspase-3. We also showed that NGN increased HO-1 expression. NGN treatment caused nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2). NGN activated both ERK and PI3 K/Akt, and treatments with the specific ERK inhibitor PD98059, the PI3 K inhibitor LY294002, and the specific Nrf2 shRNA suppressed the NGN-induced HO-1 expression. The HO-1 inhibitor ZnPP abolished the neuroprotective effect of NGN against H2O2-induced neurotoxicity. Taken together, the present study demonstrates that regulation of Nrf2/HO-1 pathway through activation of ERK and PI3 K/Akt, and the inhibition of mitochondria-dependent apoptosis together may render NGN protect SH-SY5Y cells from H2O2-induced neurotoxicity.
KeywordsNaringenin Nrf2 Heme oxygenase-1 Oxidative stress Neuroprotection
This work was supported in part by the National Key Research and Development Program of China (2016YFC1306203).
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