Eriodictyol protects against H2O2-induced neuron-like PC12 cell death through activation of Nrf2/ARE signaling pathway

Eriodictyol, a flavonoid isolated from the Chinese herb Dracocephalum rupestre has long been established as an antioxidant. The present study was designed to explore the protective effects of eriodictyol against hydrogen peroxide (H2O2)-induced neurotoxicity with cultured rat pheochromocytoma cells (PC12 cells) and the possible mechanisms involved. For this purpose, differentiated PC12 cells were cultured and exposed to 200 mu M H2O2 in the absence or presence of eriodictyol (20, 40 and 80 mu M). In addition, the potential contribution of the Nrf2/ARE neuroprotective pathway in eriodictyol-mediated protection against H2O2-induced neurotoxicity was also investigated. The results showed that H2O2-induced cell death can be inhibited in the presence of eriodictyol as measured by assays for MIT and apoptosis. Further study revealed that eriodictyol induced the nuclear translocation of Nrf2, enhanced the expression of home oxygenase (HO-1) and gamma-glutamylcysteine synthetase (gamma-GCS), and increased the levels of intracellular glutathione. Treatment of PC12 cells with Nrf2 small interference RNA abolished eriodictyol-induced HO-1 and gamma-GCS expression and its protective effects. In conclusion, these results suggest that eriodictyol upregulates HO-1 and gamma-GCS expression through the activation of Nrf2/ARE pathway and protects PC12 cells against H2O2-induced oxidative stress. (C) 2012 Elsevier Ltd. All rights reserved.