Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes

Int Immunopharmacol. 2013 Feb;15(2):400-5. doi: 10.1016/j.intimp.2013.01.003. Epub 2013 Jan 22.


Background: It has recently been reported that the polyphenol curcumin has pronounced anti-carcinogenic, anti-inflammatory and pro-apoptotic properties. This study investigated possible anti-inflammatory and apoptotic effects of curcumin on the human synovial fibroblast cell line MH7A, and on fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis (RA).

Methods: MH7A cells and RA-FLS were stimulated either with interleukin (IL)-1β or phorbol 12-myristate 13 acetate (PMA), and treated simultaneously or sequentially with increasing concentrations of curcumin. Release of interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A was quantified by enzyme-linked immunosorbent assays (ELISAs). In MH7A cells, modulation of the transcription factor nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs) such as p38 and extracellular-signal regulated kinase (ERK1/2) were analysed by a reporter gene assay and Western blot, respectively. Pro-apoptotic events were monitored by Annexin-V/7-AAD based assay. Cleavage of pro-caspase-3 and -7 was checked with specific antibodies.

Results: Curcumin effectively blocked IL-1β and PMA-induced IL-6 expression both in MH7A cells and RA-FLS. VEGF-A expression could only be detected in RA-FLS and was induced by PMA, but not by IL-1β. Furthermore, curcumin inhibited activation of NF-κB and induced dephosphorylation of ERK1/2. Treatment of FLS with high concentrations of curcumin was associated with a decrease in cell viability and induction of apoptosis.

Conclusion: The natural compound curcumin represents strong anti-inflammatory properties and induces apoptosis in FLS. This study provides an insight into possible molecular mechanisms of this substance and suggests it as a natural remedy for the treatment of chronic inflammatory diseases like RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Apoptosis / drug effects
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Cell Line
  • Curcumin / administration & dosage*
  • Curcumin / adverse effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibroblasts / drug effects*
  • Fibroblasts / pathology
  • Humans
  • Interleukin-1beta / immunology
  • Interleukin-6 / metabolism
  • NF-kappa B / metabolism
  • Polyphenols / administration & dosage*
  • Polyphenols / adverse effects
  • Synovial Membrane / pathology
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / immunology
  • Vascular Endothelial Growth Factor A / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Polyphenols
  • Vascular Endothelial Growth Factor A
  • 4-O-methyl-12-O-tetradecanoylphorbol 13-acetate
  • Extracellular Signal-Regulated MAP Kinases
  • Curcumin
  • Tetradecanoylphorbol Acetate