title: Plumbagin prevents osteoarthritis in human chondrocytes through Nrf-2 activation.
abstract: Osteoarthritis (OA) is an inflammatory disorder dealing with the focal degradation of articular cartilage. Oxidative stress and inflammation are the major events in OA. The present study aimed at identifying the mechanism of the potent antioxidant, plumbagin, in protecting against hydrogen peroxide (H2O2)‑induced chondrocyte oxidative stress and inflammatory signaling. Oxidative stress was determined by measuring reactive oxygen species, lipid peroxidation, non‑enzymic (glutathione; GSH) and enzymic antioxidant activities (GSH, glutathione S‑transferase, glutathione peroxidase, superoxide dismutase, catalase). Expression levels of nuclear factor (erythroid‑derived 2)‑like 2 (Nrf‑2), heme oxygenase 1 (HO‑1), NAD(P)H:quinone oxidoreductase 1 (NQO‑1), nuclear factor‑κB (NF‑κB), cyclooxygenase‑2 (COX‑2) and inducible NO synthase (iNOS) were determined by western blot analysis. Pro‑inflammatory cytokine expression levels were assessed using ELISA. Results from reactive oxygen species generation, lipid peroxidation content and antioxidant enzyme activities demonstrated that plumbagin significantly inhibited oxidative stress status in H2O2‑induced chondrocytes. In addition, plumbagin modulated transcription factors involved in redox and inflammation regulation, including NF‑κB and Nrf‑2, by nuclear expression. plumbagin enhanced antioxidant status by increasing the expression levels of Nrf‑2 target genes, including HO‑1 and NQO‑1. An anti‑inflammatory effect against chondrocyte‑induced inflammation was demonstrated by downregulating COX‑2, iNOS and pro‑inflammatory cytokine expression levels (tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑8). The present study identified strong evidence for a protective role of plumbagin against H2O2-induced oxidative stress and inflammation in chondrocytes by modulating redox signaling transcription factors.
authors.affiliation: Department of Orthopedics, The Second People's Hospital of Liaocheng, Affiliated Hospital of Taishan Medical University, Linqing, Shandong 252600, P.R. China.
authors.forename: Yong-Xian
authors.initials: YX
authors.lastname: Guo
authors.affiliation: Department II of Orthopedics, Linzi District People's Hospital, Zibo, Shandong 255400, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Linqing City People's Hospital, Linqing, Shandong 252600, P.R. China.
authors.forename: Dong-Zhan
authors.initials: DZ
authors.lastname: Yan
authors.affiliation: Department of Orthopedics, The Third People's Hospital of Chongqing, Chongqing 400014, P.R. China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Guo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D006861:Hydrogen Peroxide / Q000276:immunology; D051267:NF-E2-Related Factor 2 / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D009285:Naphthoquinones / Q000494:pharmacology*; D010003:Osteoarthritis / Q000276:immunology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D009285:Naphthoquinones; D006861:Hydrogen Peroxide; C014758:plumbagin