title: Protective effects of total flavonoids of Astragalus against adjuvant-induced arthritis in rats by regulating OPG/RANKL/NF-κB pathway.
abstract: BACKGROUND
  Astragalus membranaceus Bunge is one of the oldest and most frequently used crude herbs in traditional Chinese medicine. The total flavonoids of Astragalus (TFA) are the main active components isolated from Astragalus membranaceus Bunge. Our recent study has shown its potential immunomodulatory and anti-inflammatory effects in vivo and in vitro. However, its anti-arthritic effects and mechanisms of action involved have not been elucidated. The aim of this study was to evaluate the protective effects and possible mechanisms of TFA on Freund's complete adjuvant (FCA)-induced arthritis in rats.
  
  
  METHODS
  Wistar rats were intradermally injected FCA into the right hind metatarsal footpads to establish adjuvant-arthritic model. The rats were intragastrically administered daily with TFA at 25, 50 and 100mg/kg for 28days after FCA induction. Body weight, primary paw swelling, arthritis index, thymus and spleen indices were measured. The levels of serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, prostaglandin (PG)E2, osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were determined using ELISA. Histopathological changes and scores in joint tissues were examined using hematoxylin and eosin (H&E). The expression of nuclear factor (NF)-κB p65 in synovial tissues was assayed using immunohistochemical method.
  
  
  RESULTS
  TFA significantly increased body weight, attenuated primary paw swelling and arthritis index, decreased thymus and spleen indices of rats induced by FCA. Furthermore, TFA significantly inhibited serum TNF-α, IL-1β, PGE2and RANKL production, and promoted serum OPG production and OPG/RANKL ratio of rats induced by FCA. Histopathological examination indicated that TFA significantly attenuated inflammatory cell infiltration, synovial hyperplasia, pannus formation, and bone and cartilage damage. Immunohistochemical assay indicated that TFA inhibited NF-κB p65 expression in synovial tissues of rats induced by FCA.
  
  
  CONCLUSIONS
  These results suggest that TFA exerts potential protective effects against FCA-induced arthritis in rats by regulating OPG/RANKL/NF-κB pathway.
authors.affiliation: Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.affiliation: Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China.
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Li
authors.affiliation: Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China.
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China. Electronic address: zhangxm@ybu.edu.cn.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D027883:Astragalus Plant / Q000276:immunology*; D015232:Dinoprostone / Q000097:blood; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D008516:Medicine, Chinese Traditional; D016328:NF-kappa B / Q000378:metabolism; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D053583:Interleukin-1beta; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone
keywords: Adjuvant arthritis; OPG/RANKL/NF-κB pathway; Rats; Total flavonoids of Astragalus (TFA)