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

Together, our results show that plumbagin modulated NF-κB and Nrf-2 signaling. Thus, plumbagin might be an effective compound in preventing H2O2-induced neurotoxicity and its associated inflammatory responses.

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.

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.

The results showed that plumbagin increased (p < 0.01) the cell viability against H2O2-induced cell death in PC12 cells. Plumbagin effectively ameliorated H2O2-induced oxidative stress through reducing oxidative stress (p < 0.01) and activating p-Nrf-2 levels. Further, plumbagin up-regulated antioxidant enzyme activities (p < 0.01) against H2O2-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 (p < 0.01) inflammatory cytokine expression against H2O2-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 H2O2-induced neurotoxicity and its associated inflammatory responses.