BASIC RESEARCH
Plumbagin protects against hydrogen peroxide-induced neurotoxicity by modulating NF-κB and Nrf-2
 
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Submission date: 2016-04-16
Final revision date: 2016-08-07
Acceptance date: 2016-08-23
Online publication date: 2016-12-20
Publication date: 2018-08-07
 
Arch Med Sci 2018;14(5):1112–1118
 
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ABSTRACT
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 H2O2-induced neurotoxicity in PC12 cells by determining nuclear factor B (NF-B) 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-B 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-B p65, cyclooxygenase-2 (COX-2) and interleukin (IL-6, IL-8, and MCP-1) expression.

Results:
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-B p65 activation and down-regulating NF-B 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-B and Nrf-2 signaling. Thus, plumbagin might be an effective compound in preventing H2O2-induced neurotoxicity and its associated inflammatory responses.

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ISSN:1734-1922