Ginsenoside Rg1 protects against hydrogen peroxide-induced cell death in PC12 cells via inhibiting NF-κB activation

Oxidative stress is a major cause in neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and cerebral ischemia. Ginsenoside Rg1, a natural product extracted from Panax ginseng C.A. Meyer, has been reported to exert notable neuroprotective activities, which partly ascribed to its antioxidative activity. However, its molecular mechanism against oxidative stress induced by exogenous hydrogen peroxide (H2O2) remained unclear. In this study, we investigated its effect on H2O2-induced cell death and explored possible signaling pathway in PC12 cells. We proved that pretreatment with Rg1 at concentrations of 0.1-10 mu M remarkably reduced the cytotoxicity induced by 400 mu M of H2O2 in PC12 cells by MTT and Hoechst and PI double staining assay. Of note, we demonstrated the activation of NF-kappa B signaling pathway induced by H2O2 thoroughly in PC12 cells, and Rg1 suppressed phosphorylation and nuclear translocation of NF-kappa B/p65, phosphorylation and degradation of inhibitor protein of kappa B (I kappa B) as well as the phosphorylation of I kappa B-kinase complex (IKK) by western blotting or indirect immunofluorescence assay. Besides. Rg1 also inhibited the activation of Akt and the extracellular signal-regulated kinase 1/2 (ERK1/2). Furthermore, the protection of Rg1 on H2O2-injured PC12 cells was attenuated by pretreatment with two NF-kappa B pathway inhibitors (JSH-23 or BOT-64). In conclusion, our results suggest that Rg1 could rescue the cell injury by H2O2 via down-regulation NF-kappa B signaling pathway as well as Akt and ERK1/2 activation, which put new evidence on the neuroprotective mechanism of Rg1 against the oxidative stress and the regulatory role of H2O2 in NF-kappa B pathway in PC12 cells. (C) 2010 Elsevier Ltd. All rights reserved.