title: Kirenol upregulates nuclear annexin-1 which interacts with NF-κB to attenuate synovial inflammation of collagen-induced arthritis in rats.
abstract: BACKGROUND
  Kirenol is a diterpenoid compound purified from the Chinese Herba Siegesbeckiae. Siegesbeckiae has been employed for the treatment of arthritis for centuries, its safety and efficacy are documented through a long history of human use.
  
  
  OBJECTIVE
  To investigate the effects on collagen-induced arthritis (CIA) and anti-inflammatory mechanism of kirenol.
  
  
  METHODS
  Kirenol was administrated intragastrically in rats after the onset of CIA. Pathological changes were evaluated by paw swelling and histopathology. Concentration of IL-1β in synovial fluid and adrenal corticotropin (ACTH) in plasma were determined by Elisa. Western blot was performed to detect the expression of annexin-1 and glucocorticoid receptor alpha (GRα) in synovium. NF-κB DNA binding activity was assessed by electrophoretic mobility shift assays (EMSA).
  
  
  RESULTS
  Kirenol (1, 2, and 4 mg/kg) and prednisolone depressed paw swelling and reduced IL-1β of synovial fluid in the CIA rats (p<0.05 or p<0.01). Kirenol and prednisolone upregulated nuclear annexin-1 and inhibited NF-κB activity in synovium of CIA. The inhibitory effect of kirenol and prednisolone on NF-κB activity was enhanced by anti-annexin-1 Ab. Prednisolone, but not kirenol, downregulated plasma ACTH and GRα expression significantly (p<0.01).
  
  
  CONCLUSIONS
  Kirenol and prednisolone can upregulate nuclear annexin-1 which interacts with NF-κB to inhibit NF-κB activity, reduce cytokines expression and thereby attenuate inflammation of CIA joints. Kirenol does not lead to ACTH or GR downregulation, which is in contrast to classic glucocorticoid prednisolone. Kirenol shares with GCs similar anti-inflammatory mechanism but bypass the considerable limitation of GCs treatment.
authors: Department of Integrated Chinese Traditional with Western Medicine, Peking University Health Science Center, Beijing 100191, PR China. wangzheming@bjmu.edu.cn
authors: Zhe-Ming
authors: ZM
authors: Wang
authors: Shi-Gong
authors: SG
authors: Zhu
authors: Zai-Wang
authors: ZW
authors: Wu
authors: Yue
authors: Y
authors: Lu
authors: Hong-Zheng
authors: HZ
authors: Fu
authors: Rui-Qin
authors: RQ
authors: Qian
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001665:Binding Sites; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D024043:Collagen Type II; D004247:DNA / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D004224:Diterpenes; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C560087:kirenol; D000324:Adrenocorticotropic Hormone; D004247:DNA; D011239:Prednisolone