title: Plumbagin exerts protective effects in nucleus pulposus cells by attenuating hydrogen peroxide-induced oxidative stress, inflammation and apoptosis through NF-κB and Nrf-2.
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.
authors.affiliation: Department of Orthopedics, The 100th Hospital of Chinese People's Liberation Army, Suzhou, Jiangsu 215007, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Orthopedics, The 100th Hospital of Chinese People's Liberation Army, Suzhou, Jiangsu 215007, P.R. China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, The 100th Hospital of Chinese People's Liberation Army, Suzhou, Jiangsu 215007, P.R. China.
authors.forename: Ding
authors.initials: D
authors.lastname: Ren
authors.affiliation: Department of Orthopedics, The 100th Hospital of Chinese People's Liberation Army, Suzhou, Jiangsu 215007, P.R. China.
authors.forename: Kejun
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, The 100th Hospital of Chinese People's Liberation Army, Suzhou, Jiangsu 215007, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007249:Inflammation; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D000070614:Nucleus Pulposus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002374:Catalase; D005978:Glutathione; D005979:Glutathione Peroxidase; D006861:Hydrogen Peroxide; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D009285:Naphthoquinones; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; C495637:Nfe2l2 protein, rat; C014758:plumbagin