title: The effects of arctigenin on human rheumatoid arthritis fibroblast-like synoviocytes.
abstract: BACKGROUND
  Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) play an important role in the initiation and progression of RA, which are resistant to apoptosis and proliferate in an anchorage-independent manner.
  
  
  OBJECTIVE
  The effects of arctigenin on the proliferation and apoptosis of RAFLSs were explored.
  
  
  METHODS
  Arctigenin (0-160 µM) was used to treat RAFLSs for 48 h. Cell viability and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining. Western blot analysis was performed to detect the changes in apoptosis-related genes.
  
  
  CONCLUSIONS
  Arctigenin decreased cell viability by 23, 30, and 38% at the dose of 10, 20, and 30 µM, respectively. The half maximal inhibitory concentration (IC50) of arctignein on RAFLSs was about 38 µM. Moreover, 9, 15, and 21% of RAFLSs are induced apoptosis by 10, 20, and 30 µM of arctigenin. The apoptotic response was due to the loss of mitochondrial membrane potential, coupled with the release of cytochrome C into cytoplasm, the up-regulation of pro-apoptotic protein, Bax, and down-regulation of antiapoptotic protein, B cell lymphoma 2 (Bcl-2). The activation of mitochondrial pathway in arctigenin-treated RAFLSs induced the cleavage of caspase-9, caspase-3, and poly (ADP-ribose) polymerase (PARP). Additionally, arctigenin inhibited the nuclear translocation of p65, decreased the degradation of inhibitor of kappa B alpha (IκBα), and attenuated the phosphorylation of Akt.
  
  
  CONCLUSIONS
  Our results reveal that arctigenin inhibits cell proliferation and induces mitochondrial apoptosis of RAFLSs, which is associated with the modulation of NF-κB and Akt signaling pathways.
authors.affiliation: Department of Orthopedics, The 97th Hospital of People's Liberation Army , Xuzhou, Jiangsu , China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Cai
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology*; D005663:Furans / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000166:cytology* / Q000187:drug effects*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects
chemical_list: D005663:Furans; D017705:Lignans; C071942:arctigenin
keywords: Akt; mitochondrial signaling pathway; nuclear factor kappa B; proliferation