Plumbagin protects against hydrogen peroxide-induced neurotoxicity by modulating NF-κB and Nrf-2.

Introduction: Redox signaling initiates pathogenesis of neuronal degeneration. Plumbagin is a potential antioxidant with anti-inflammatory, anti-cancer and radio sensitizing properties. In the present study, we aimed to determine the protective role of plumbagin against HO-induced neurotoxicity in PC12 cells by determining nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (Nrf-2) pathways.

Material And Methods: We analyzed oxidative stress by determining reactive oxygen species (ROS) and nitrite levels, and antioxidant enzyme activities. Nrf-2 and NF-κB p65 nuclear localization was determined through immunofluorescence. Further, nuclear levels of p-Nrf-2 and downstream expression of NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase-1 (HO-1) and glutathione-s-transferase (GST) were determined by western blot. Anti-inflammatory activity was analyzed by evaluating NF-κB p65, cyclooxygenase-2 (COX-2) and interleukin (IL-6, IL-8, and MCP-1) expression.

Results: The results showed that plumbagin increased ( < 0.01) the cell viability against HO-induced cell death in PC12 cells. Plumbagin effectively ameliorated HO-induced oxidative stress through reducing oxidative stress ( < 0.01) and activating p-Nrf-2 levels. Further, plumbagin up-regulated antioxidant enzyme activities ( < 0.01) against HO-induced oxidative stress. Plumbagin showed anti-inflammatory effect by suppressing NF-κB p65 activation and down-regulating NF-κB p65 and COX-2 expression. In addition, plumbagin modulated ( < 0.01) inflammatory cytokine expression against HO-induced neurotoxic effects.

Conclusions: Together, our results show that plumbagin modulated NF-κB and Nrf-2 signaling. Thus, plumbagin might be an effective compound in preventing HO-induced neurotoxicity and its associated inflammatory responses.