Cordycepin inhibits IL-1beta-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts

Rheumatology (Oxford). 2009 Jan;48(1):45-8. doi: 10.1093/rheumatology/ken417.


Objective: MMP is a key enzyme in the degradation of extracellular matrices, and its expression plays important roles in inflammatory diseases. Cordycepin (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has been shown to exhibit many pharmacological activities, such as anti-cancer, anti-inflammatory and anti-infection activities. In this study, we aimed at the inhibitory effect of cordycepin on IL-1beta-induced MMP-1 and MMP-3 expression as well as the molecular basis using RA synovial fibroblasts (RASFs).

Methods: RASFs were isolated from synovial tissue obtained from 12 patients with RA and cultured in monolayer. Expression of MMP-1 and MMP-3 was evaluated using western blotting and real-time PCR. Chemokines were analysed by ELISA. The phosphorylation of mitogen-activated protein kinase was measured by western blotting. Electrophoretic mobility shift assay was performed to evaluate binding activities of DNA to nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1).

Results: Cordycepin inhibited IL-1beta-induced MMP-1 and MMP-3 expressions in RASFs in a dose-dependent manner. Among various chemokines [such as monocyte chemoattractant protein-1 (MCP-1), GRO-alpha, regulated upon activation, normal T-cell expressed and presumably secreted (RANTES) and epithelial neutrophil activating peptide 78 (ENA-78)], cordycepin specifically blocked IL-1beta-induced ENA-78 production in RASF. Moreover, cordycepin significantly inhibited IL-1beta-induced p38/JNK and AP-1 activation, but not extracellular signal-regulated kinase (ERK) and NF-kappaB activation.

Conclusions: Cordycepin is a potent inhibitor of IL-1beta-induced chemokine production and MMP expression and strongly blocks the p38/JNK/AP-1 signalling pathway in RASFs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / pharmacology*
  • Arthritis, Rheumatoid / enzymology*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemokines / biosynthesis
  • DNA-Binding Proteins / metabolism
  • Deoxyadenosines / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Fibroblasts / pathology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Interleukin-1beta / antagonists & inhibitors*
  • Interleukin-1beta / pharmacology
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 3 / biosynthesis*
  • Matrix Metalloproteinase 3 / genetics
  • NF-kappa B / metabolism
  • Synovial Membrane / drug effects
  • Synovial Membrane / enzymology
  • Synovial Membrane / pathology
  • Transcription Factor AP-1 / metabolism
  • Up-Regulation / drug effects


  • Antirheumatic Agents
  • Chemokines
  • DNA-Binding Proteins
  • Deoxyadenosines
  • Interleukin-1beta
  • NF-kappa B
  • Transcription Factor AP-1
  • Matrix Metalloproteinase 3
  • MMP1 protein, human
  • Matrix Metalloproteinase 1
  • cordycepin