Abstract
Plumbagin, one of the constituents responsible for the various biological activities of Plumbago zeylanica has been demonstrated to possess antioxidant activity, which may inhibit lipid peroxidation in a dose- and time-dependent manner. In the present study, we aimed to examine the protective effects of plumbagin as well as the underlying mechansim through which plumbagin attenuates hydrogen peroxide (H2O2)-induced oxidative stress in nucleus pulposus cells (NPCs). For this purpose, the NPCs were incubated with fresh medium containing H2O2 (200 µM) at 37˚C in a humidified 5% CO2 atmosphere for 6 h, and cultured with various concentrations of plumbagin (0, 0.5, 1, 2, 5, 10 and 20 µM). Treatment with plumbagin significantly increased the viability of the H2O2-exposed NPCs in a dose‑dependent manner. Moreover, plumbagin significantly reduced the generation of reactive oxygen species, lipid peroxidation, as well as the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in the H2O2‑exposed NPCs. Glutathione (GSH) content, as well as the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxdiase (GSH-Px) were increased. We found that the administration of plumbagin significantly inhibited the activity of caspase-9 and -3, and downregulated NF-κB expression and upregulated Nrf-2 expression in the H2O2-exposed NPCs. Taken together, these findings suggest that plumbagin exerts neuroprotective effects in NPCs by attenuating H2O2‑induced oxidative stress, inflammation and apoptosis through mediating the expression of NF-κB and Nrf-2.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Apoptosis / drug effects
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Catalase / genetics
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Catalase / metabolism
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Chondrocytes / drug effects*
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Chondrocytes / metabolism
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Chondrocytes / pathology
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Dose-Response Relationship, Drug
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Gene Expression Regulation
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Glutathione / metabolism
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Glutathione Peroxidase / genetics
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Glutathione Peroxidase / metabolism
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Hydrogen Peroxide / antagonists & inhibitors*
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Hydrogen Peroxide / pharmacology
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Inflammation
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Male
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NF-E2-Related Factor 2 / agonists*
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NF-E2-Related Factor 2 / genetics
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NF-E2-Related Factor 2 / metabolism
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NF-kappa B / agonists*
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Naphthoquinones / pharmacology*
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Nucleus Pulposus / drug effects
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Nucleus Pulposus / metabolism
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Nucleus Pulposus / pathology
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Osteoblasts / drug effects*
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Osteoblasts / metabolism
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Osteoblasts / pathology
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Oxidative Stress
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Primary Cell Culture
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species / antagonists & inhibitors
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Reactive Oxygen Species / metabolism
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Signal Transduction
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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NF-E2-Related Factor 2
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NF-kappa B
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Naphthoquinones
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Nfe2l2 protein, rat
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Phosphoinositide-3 Kinase Inhibitors
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Reactive Oxygen Species
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Hydrogen Peroxide
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Catalase
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Glutathione Peroxidase
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Superoxide Dismutase
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Proto-Oncogene Proteins c-akt
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Glutathione
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plumbagin