title: Sulfuretin, a major flavonoid isolated from Rhus verniciflua, ameliorates experimental arthritis in mice.
abstract: OBJECTIVE
  Sulfuretin, a major flavonoid isolated from Rhus verniciflua, is known to have anti-inflammatory effects. However, the mechanisms underlying the anti-inflammatory effect of sulfuretin on rheumatoid arthritis have not been elucidated. In this study we investigated whether sulfuretin treatment modulates the severity of arthritis in an experimental model.
  
  
  METHODS
  We evaluated the effects of sulfuretin on tumor necrosis factor-α (TNF-α)-treated human rheumatoid fibroblast-like synoviocytes (FLS) in vitro and on collagen-induced arthritis (CIA) mice in vivo.
  
  
  RESULTS
  In vitro experiments demonstrated that sulfuretin suppressed the chemokine production, matrix metalloproteinase secretion, and cell proliferation induced by tumor necrosis factor-α in rheumatoid FLS. In addition, sulfuretin inhibited the osteoclast differentiation induced by macrophage colony-stimulating factor and receptor activator of NF-κB ligand in bone marrow macrophages. In mice with CIA, early intervention with sulfuretin prevented joint destruction, as evidenced by a lower cumulative disease incidence and an absence of diverse disease features based on hind paw thickness, radiologic and histopathologic findings, and inflammatory cytokine levels. In mice with established arthritis, sulfuretin treatment significantly reduced synovial inflammation and joint destruction. The in vitro and in vivo protective effects of sulfuretin were mediated by inhibition of the NF-κB signaling pathway.
  
  
  CONCLUSIONS
  These results suggest that using sulfuretin to block the NF-κB pathway in rheumatoid joints reduces both inflammatory responses and joint destruction. Therefore, sulfuretin may have therapeutic value in preventing or delaying the progression of rheumatoid arthritis.
authors.affiliation: Department of Oral Biochmistry, Wonkwang University School of Dentistry, 460 Iksan-daero, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Hwang
authors.forename: Hyoung-Won
authors.initials: HW
authors.lastname: Koh
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Ju Hong
authors.initials: JH
authors.lastname: Lee
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
mesh_terms: D000818:Animals; D000963:Antimetabolites; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001572:Benzofurans / Q000494:pharmacology*; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D003094:Collagen; D016207:Cytokines / Q000096:biosynthesis; D024202:Electrophoretic Mobility Shift Assay; D005419:Flavonoids / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects; D029045:Rhus / Q000737:chemistry*; D013583:Synovial Membrane / Q000166:cytology; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000963:Antimetabolites; D001572:Benzofurans; D018925:Chemokines; D016207:Cytokines; D005419:Flavonoids; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D020782:Matrix Metalloproteinases; D001973:Bromodeoxyuridine; C054989:sulfuretin