LAUSR

&bgr;-Amyloid (A&bgr;) species probably exert neurotoxic effects in Alzheimer’s disease. In the present study, the effect of antioxidant plumbagin was tested against A&bgr;25–35-induced neurotoxicity in the SH-SY5Y cell line. Cell viability was determined using an MTT assay. Antioxidant status was analyzed through antioxidant enzyme activities, nuclear factor erythroid 2-related factor 2 (Nrf-2), and its downstream protein expressions. Inflammatory response was determined through nuclear factor-&kgr;B (NF-&kgr;B) pathway and cytokine expressions. A&bgr;25–35 showed a decrease in cell viability in a concentration-dependent manner. The IC50 value was found to be 17 µM. Pretreatment with plumbagin prevented A&bgr;25–35-induced toxicity by improving the cell viability up to 96%. Plumbagin inhibited A&bgr;25–35-induced oxidative stress by decreasing reactive oxygen species and lipid peroxidation. A&bgr;25–35-induced redox imbalance caused decreased Nrf-2 expression, with downregulation Nrf-2 target proteins heme oxygenase 1 and NAD(P)H dehydrogenase (quinone 1) during A&bgr;25–35 treatment. However, plumbagin improved the antioxidant defense system by increasing Nrf-2 expression with concomitant upregulation in heme oxygenase 1 and NAD(P)H dehydrogenase (quinone 1). A&bgr;25–35 induced inflammatory response through upregulated NF-&kgr;B, cyclooxygenase-2, and inducible nitric oxide synthase levels. Plumbagin exerted anti-inflammatory effects by decreasing NF-&kgr;B, cyclooxygenase-2, and inducible nitric oxide synthase levels. A&bgr;25–35-induced increases in proinflammatory cytokine (interleukin-8, interleukin-6, and monocyte chemoattractant protein-1) expressions were suppressed by plumbagin pretreatment. Altogether, the present study indicates that plumbagin prevents redox status and inflammatory activation during A&bgr;25–35-induced toxicity by modulating the antioxidant defense system and Nrf-2 signaling.