PMID- 27082014 OWN - NLM STAT- MEDLINE DCOM- 20170228 LR - 20191210 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 37 IP - 6 DP - 2016 Jun TI - Plumbagin exerts protective effects in nucleus pulposus cells by attenuating hydrogen peroxide-induced oxidative stress, inflammation and apoptosis through NF-kappaB and Nrf-2. PG - 1669-76 LID - 10.3892/ijmm.2016.2564 [doi] AB - 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 microM) 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 microM). 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-alpha (TNF-alpha), interleukin (IL)-1beta 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-kappaB 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-kappaB and Nrf-2. FAU - Chu, Hui AU - Chu H AD - Department of Orthopedics, The 100th Hospital of Chinese People's Liberation Army, Suzhou, Jiangsu 215007, P.R. China. FAU - Yu, Hang AU - Yu H AD - Department of Orthopedics, The 100th Hospital of Chinese People's Liberation Army, Suzhou, Jiangsu 215007, P.R. China. FAU - Ren, Ding AU - Ren D AD - Department of Orthopedics, The 100th Hospital of Chinese People's Liberation Army, Suzhou, Jiangsu 215007, P.R. China. FAU - Zhu, Kejun AU - Zhu K AD - Department of Orthopedics, The 100th Hospital of Chinese People's Liberation Army, Suzhou, Jiangsu 215007, P.R. China. FAU - Huang, Hong AU - Huang H AD - Department of Orthopedics, The 100th Hospital of Chinese People's Liberation Army, Suzhou, Jiangsu 215007, P.R. China. LA - eng PT - Journal Article DEP - 20160414 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (Naphthoquinones) RN - 0 (Nfe2l2 protein, rat) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Reactive Oxygen Species) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.11.1.6 (Catalase) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - GAN16C9B8O (Glutathione) RN - YAS4TBQ4OQ (plumbagin) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Apoptosis/drug effects MH - Catalase/genetics/metabolism MH - Chondrocytes/*drug effects/metabolism/pathology MH - Dose-Response Relationship, Drug MH - Gene Expression Regulation MH - Glutathione/metabolism MH - Glutathione Peroxidase/genetics/metabolism MH - Hydrogen Peroxide/*antagonists & inhibitors/pharmacology MH - Inflammation MH - Male MH - NF-E2-Related Factor 2/*agonists/genetics/metabolism MH - NF-kappa B/*agonists/genetics/metabolism MH - Naphthoquinones/*pharmacology MH - Nucleus Pulposus/drug effects/metabolism/pathology MH - Osteoblasts/*drug effects/metabolism/pathology MH - Oxidative Stress MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Primary Cell Culture MH - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/antagonists & inhibitors/metabolism MH - Signal Transduction MH - Superoxide Dismutase/genetics/metabolism EDAT- 2016/04/16 06:00 MHDA- 2017/03/01 06:00 CRDT- 2016/04/16 06:00 PHST- 2015/04/20 00:00 [received] PHST- 2016/04/01 00:00 [accepted] PHST- 2016/04/16 06:00 [entrez] PHST- 2016/04/16 06:00 [pubmed] PHST- 2017/03/01 06:00 [medline] AID - 10.3892/ijmm.2016.2564 [doi] PST - ppublish SO - Int J Mol Med. 2016 Jun;37(6):1669-76. doi: 10.3892/ijmm.2016.2564. Epub 2016 Apr 14.