title: β-Elemene induces apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes via reactive oxygen species-dependent activation of p38 mitogen-activated protein kinase.
abstract: BACKGROUND
  β-Elemene is a natural anticancer compound extracted from the Chinese medicinal herb Curcuma Wenyujin. This study was done to determine the effect of β-elemene on the apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and associated molecular mechanisms.
  
  
  METHODS
  RA-FLS were treated for 72h with β-elemene at 10-200μg/ml and cell viability and apoptotic changes were examined. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) was checked.
  
  
  RESULTS
  We found that β-elemene significantly inhibited the viability and promoted apoptosis of RA-FLS in a concentration-dependent fashion. β-Elemene-treated FLS showed a significant decline in mitochondrial membrane potential, an accumulation of cytochrome c in the cytosol, and increased activities of caspase-9 and caspase-3. β-Elemene treatment caused an enhancement of p38 MAPK phosphorylation and ROS production. The pro-apoptotic activity of β-elemene was significantly reversed by pretreatment with the p38 inhibitor SB203580 or ROS inhibitor N-acetyl-l-cysteine.
  
  
  CONCLUSIONS
  Taken together, β-elemene is effective in inducing mitochondrial apoptosis of RA-FLS, which is mediated through induction of ROS formation and p38 MAPK activation. β-Elemene may thus have therapeutic benefits for RA.
authors.affiliation: Department of Burn and Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Zou
authors.affiliation: Department of Burn and Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Changyin
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Burn and Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: zhengjuncui2006@163.com.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Department of Burn and Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Burn and Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Qingnan
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Burn and Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Burn and Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Burn and Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Gaoyuan
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Burn and Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Han
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D013583:Synovial Membrane / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C445979:beta-elemene; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; Oxidative stress; Rheumatoid arthritis; β-Elemene