Ethyl acetate fraction from Cudrania tricuspidata inhibits IL-1β-induced rheumatoid synovial fibroblast proliferation and MMPs, COX-2 and PGE2 production

Biol Res. 2010;43(2):225-31. Epub 2010 Sep 24.

Abstract

Objectives: The objective of this study is to determine the effects of Ethyl acetate fraction from Cudrania tricuspidata (EACT) on the interleukin-1b (IL-1b)-induced proliferation of rheumatoid synovial fibroblasts (RASFs) and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) and prostaglandin E2 (PGE2) by RASFs.

Materials and methods: The proliferation of RASFs was evaluated with CCK-8 reagent in the presence of IL-1b with/without EACT. The expression of MMPs, TIMP-1, COXs, PGE2 and intracellular MAPK signalings, including p-ERK, p-p38, p-JNK and NF-kB were examined by immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and ELISA in conditions as described above.

Results: EACT inhibits IL-1β-induced proliferation of RASFs and MMP-1, 3, COX-2 mRNA and protein expression, PGE2 production induced with IL-1b. EACT also inhibits the phosphorylation of ERK-1/2, p38, JNK and activation of NF-kB by IL-1b.

Conclusions: These results suggest that EACT might be involved in synovial fibroblast proliferation and MMPs, COX-2, and PGE2 production, which are involved in joint destruction in rheumatoid arthritis (RA), indicating that this might be a new therapeutic modality for management of rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology*
  • Arthritis, Rheumatoid / pathology*
  • Cell Proliferation / drug effects
  • Cyclooxygenase 2 / biosynthesis
  • Dinoprostone / biosynthesis
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / drug effects*
  • Fibroblasts / pathology
  • Humans
  • Interleukin-1beta / antagonists & inhibitors*
  • Interleukin-1beta / pharmacology
  • Matrix Metalloproteinases / biosynthesis
  • Moraceae / chemistry*
  • Polymerase Chain Reaction

Substances

  • Acetates
  • Interleukin-1beta
  • ethyl acetate
  • Cyclooxygenase 2
  • Matrix Metalloproteinases
  • Dinoprostone