Anti-inflammatory effect of curcumin involves downregulation of MMP-9 in blood mononuclear cells

Curcumin (1, 7-bis(4-hydroxyl-3-methoxyphenyl)-1, 6 heptadiene-3, 5-dione) is a potent natural anti oxidant and anti-inflammatory agent, which mediates its effects mainly by inhibiting the activity of enzymes like cyclooxygenase, lipooxygenases and phospholipase A2. Here we examined the possibility of curcurnin affecting the production of matrix metalloproteinases (MMPs) by peripheral blood mononuclear cells (PBMCs), which play an important role in inflammation. Zymographic analysis and ELISA showed that curcumin significantly inhibited the activity and level of MMPs produced by PBMCs isolated from human and inflammation-induced rabbit in a concentration dependent manner. The administration of curcurnin to inflammation-induced rabbits also caused downregulation of MMP-9. Kinetic analysis showed that the effect of curcurnin was a delayed one indicating inhibition of de novo protein synthesis. RT-PCR and immunoblot analysis showed inhibition of the production of MMP-9 mRNA and protein respectively by human PBMCs, which were activated in vitro by Artocarpus Lakoocha agglutinin (ALA) lectin. EMSA and super shift showed activation of classical NF kappa B in in vitro activated PBMCs and treatment with curcumin inhibited activation of NFKB. Immunoblot analysis suggested that ALA-induced activation of NF kappa B leading to the upregulation of MMP-9 was due to the degradation of I kappa B-alpha. Curcumin inhibited the degradation of I kappa B-alpha, which inhibited the ALA mediated activation of NFKB and upiegulation of NIMP-9. These results indicated that antiinflammatory effect of curcumin also involves inhibition of the production of MMP-9 in PBMCs. (c) 2007 Elsevier B.V. All rights reserved.