title: Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated human fibroblast-like synoviocytes in vitro and in mice with collagen-induced arthritis.
abstract: OBJECTIVE
  Hyperoside is a flavonol glycoside mainly found in plants of the genera Hypericum and Crataegus, which has shown anti-oxidant, anti-cancer and anti-inflammatory activities. In this study, we investigated the effects of hyperoside on human rheumatoid fibroblast-like synoviocytes (FLSs) in vitro and on mouse collagen-induced arthritis (CIA) in vivo.
  
  
  METHODS
  FLSs were isolated from primary synovial tissues obtained from rheumatoid arthritis (RA) patients and exposed to LPS (1 μg/mL). Cell viability and proliferation were measured with MTT and BrdU assay. Cell migration was assessed using wound-healing assay and Transwell assay. DNA binding of NF-κB was measured using a TransAM-NFkappaB kit. The localization of p65 subunit was detected with immunocytochemistry. CIA was induced in mice by primary immunization with Bovine Type II collagen (CII) emulsified in CFA, followed by a booster injection 3 weeks later. The arthritic mice were treated with hyperoside (25, 50 mg·kg(-1)·d(-1), ip) for 3 weeks, and the joint tissues were harvested for histological analysis.
  
  
  RESULTS
  Hyperoside (10, 50, 100 μmol/L) dose-dependently inhibited LPS-induced proliferation and migration of human RA FLSs in vitro. Furthermore, hyperoside decreased LPS-stimulated production of TNF-α, IL-6, IL-1 and MMP-9 in the cells. Moreover, hyperoside inhibited LPS-induced phosphorylation of p65 and IκBα, and suppressed LPS-induced nuclear translocation of p65 and DNA biding of NF-κB in the cells. Three-week administration of hyperoside significantly decreased the clinical scores, and alleviated synovial hyperplasia, inflammatory cell infiltration and cartilage damage in mice with CIA.
  
  
  CONCLUSIONS
  Hyperoside inhibits LPS-induced proliferation, migration and inflammatory responses in human RA FLSs in vitro by suppressing activation of the NF-κB signaling pathway, which contributes to the therapeutic effects observed in mice with CIA.
authors.affiliation: Department of Rheumatoid Immunity, the First Affiliated Hospital.
authors.forename: Xiang-Nan
authors.initials: XN
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: En-Zhi
authors.initials: EZ
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Han-Ming
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Hai-Juan
authors.initials: HJ
authors.lastname: Sui
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Rheumatoid Immunity, the First Affiliated Hospital.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008811:Mice, Inbred DBA; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000070918:Synoviocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000072000:NF-KappaB Inhibitor alpha; C021304:hyperoside; D003094:Collagen; D011794:Quercetin