Naringenin inhibit the hydrogen peroxide-induced SH-SY5Y cells injury through Nrf2/HO-1 pathway. - GreenMedInfo Summary
Naringenin Inhibit the Hydrogen Peroxide-Induced SH-SY5Y Cells Injury Through Nrf2/HO-1 Pathway.
Neurotox Res. 2019 May 10. Epub 2019 May 10. PMID: 31076999
Yuzi Jin
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 (HO)-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and the possible mechanisms involved. Exposure of cells to 400 μM HOfor 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 HO-mediated ROS production. In addition, NGN inhibited HO-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 HO-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 HO-induced neurotoxicity.