Curcumin inhibits protease-activated receptor-2 and -4-mediated mast cell activation

Clin Chim Acta. 2003 Dec;338(1-2):135-41. doi: 10.1016/j.cccn.2003.08.015.


Background: Curcumin, a major yellow pigment and active component of turmeric powder extracted from Curcuma longa L. (Gingiberaceae), has been shown to possess anti-inflammatory and anti-cancer activities. Protease-activated receptors (PARs) play a role in inflammation, and human leukemic mast cells (HMC-1) co-express PAR2 and PAR4. In the present study, the effect of curcumin on PAR2- and PAR4-mediated HMC-1 activation was examined.

Methods: HMC-1 cells were stimulated with trypsin (100 nmol/l, PAR2 and PAR4 agonist), SLIGKV-NH(2) (100 microM, PAR2-activating peptide) or GYPGQV-NH(2) (100 micromol/l PAR4-activating peptide) in the presence or absence of curcumin (1, 10, and 100 micromol/l). TNF-alpha secretion was measured by enzyme-linked immunosorbent assay (ELISA). TNF-alpha and tryptase mRNA were measured by reverse-transcription PCR (RT-PCR). Mitogen-activated protein kinase (MAPK) activation was assessed by Western blot analysis. Trypsin activity was measured using the substrate Bz-DL-Arg-p-nitroanilide (BAPNA).

Results: Curcumin (10 and 100 micromol/l) inhibited TNF-alpha secretion from trypsin or activating peptide-stimulated HMC-1. Curcumin (10 and 100 micromol/l) also inhibited TNF-alpha and tryptase mRNA expression in trypsin-stimulated HMC-1. Furthermore, curcumin inhibited trypsin-induced extracellular signal-regulated kinase (ERK) phosphorylation. However, curcumin did not affect the trypsin activity even at 100 micromol/l.

Conclusion: Curcumin inhibits PAR2- and PAR4-mediated human mast cell activation, not by inhibition of trypsin activity but by block of ERK pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Curcumin / pharmacology*
  • Humans
  • Mast Cells / cytology
  • Mast Cells / drug effects*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Proteinase-Activated / antagonists & inhibitors*
  • Receptors, Proteinase-Activated / metabolism
  • Serine Endopeptidases / genetics
  • Trypsin / metabolism
  • Tryptases
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • RNA, Messenger
  • Receptors, Proteinase-Activated
  • Tumor Necrosis Factor-alpha
  • Mitogen-Activated Protein Kinases
  • Serine Endopeptidases
  • Trypsin
  • Tryptases
  • Curcumin