title: SND-117, a sinomenine bivalent alleviates type II collagen-induced arthritis in mice.
abstract: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that affects about 1% of the population worldwide. RA is mainly manifested by persistent synovitis and progressive joint destruction. The aim of the present study was to examine the anti-arthritis effects of SND-117, a sinomenine bivalent that is obtained from the structure modification of a clinically available anti-RA drug, sinomenine. The arthritis model (CIA) was established by immunizing DBA/1 mice with type II collagen, and the arthritis scores including inflammation, joint destruction and bone erosion were assessed after booster immunization for 3weeks. The levels of cytokines such as IL-1β, IL-6 and TNF-α were analyzed by quantitative PCR and ELISA. The TNF-α induced NF-κB activation in fibroblast-like synovial cells (FLSCs) was analyzed by Western blot. SND-117 significantly relieved the inflammatory symptoms of collagen-induced arthritis, reduced bone erosion and joint destruction in CIA mice. The serum levels of IL-1β, IL-6 and TNF-α of CIA mice were markedly decreased by SND-117. SND-117 also strongly inhibited the phosphorylation and nuclear translocation of NF-κB p65 in FLSCs upon TNF-α stimulation. These data demonstrated that SND-117 could effectively block the pathogenesis of collagen-induced arthritis in CIA mice via inhibition of NF-κB signaling, and might provide potential clinic benefits in rheumatoid arthritis management.
authors.affiliation: Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors.forename: Yu-Ren
authors.initials: YR
authors.lastname: Zhou
authors.affiliation: Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors.forename: Bei-Hua
authors.initials: BH
authors.lastname: Bao
authors.affiliation: Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. Electronic address: lijxnju@nju.edu.cn.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Li
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D007117:Immunization, Secondary; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009019:Morphinans / Q000008:administration & dosage* / Q000737:chemistry; D016328:NF-kappa B / Q000378:metabolism; D032841:Sinomenium; D013585:Synovitis / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D018501:Antirheumatic Agents; D024043:Collagen Type II; D016207:Cytokines; D018836:Inflammation Mediators; D009019:Morphinans; D016328:NF-kappa B; C009271:sinomenine
keywords: Collagen-induced arthritis; Cytokines; Fibroblast like synovial cells; NF-κB; SND-117; Sinomenine bivalent