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).
- Al-Dosari DI, Ahmed MM, Al-Rejaie SS, Alhomida AS, Ola MS (2017) Flavonoid naringenin attenuates oxidative stress, apoptosis and improves neurotrophic effects in the diabetic rat retina. Nutrients. 9Google Scholar
- Melo, A., Monteiro, L., Lima, R.M., Oliveira, D.M., Cerqueira, M.D., El-Bacha, R.S., 2011. Oxidative stress in neurodegenerative diseases: mechanisms and therapeutic perspectives. Oxidative Med Cell Longev 2011,467180, 1, 14Google Scholar
- Ortiz-Andrade RR, Sánchez-Salgado JC, Navarrete-Vázquez G, Webster SP, Binnie M, García-Jiménez S, León-Rivera I, Cigarroa-Vázquez P, Villalobos-Molina R, Estrada-Soto S (2008) Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulation. Diabetes Obes Metab 10:1097–1104CrossRefGoogle Scholar
- Scapagnini G, Butterfield DA, Colombrita C, Sultana R, Pascale A, Calabrese V (2004) Ethyl ferulate, a lipophilic polyphenol, induces HO-1 and protects rat neurons against oxidative stress. Antioxid Redox Signal 6:811–818Google Scholar