Novel Curcumin Derivatives Suppress Inflammatory Mediators in Periodontally-relevant Cells

Objectives: To determine the effect of a newer generation of chemically modified curcumin (CMC-2.24) on the production of cytokines and MMPs by cultured human mononuclear cells treated with endotoxin (lipopolysaccharide, LPS) produced by P. gingivalis, a periodontally-relevant cell culture model.

Methods: Human monocytes were isolated by density gradient centrifugation. In separate experiments, monocytes were cultured in serum containing medium for 7 days to allow for maturation. Cells were cultured in serum-free media for 18 hours in the absence or presence of LPS (50 ng/ml). Cells were treated with 2μm or 5μm CMC-2.24. Cell viability was determined using MTS. The conditioned media was analyzed for cytokine levels with ELISA and MMP-9 levels were measured using gelatin zymography.

Results: Excessive MMP-9 induced by LPS was reduced by 5 μM CMC-2.24 more than by 2 μM CMC-2.24. In monocytes, IL-1β levels were reduced by 45% and 79% after treatment with 2 or 5 μM CMC-2.24 respectively. Similarly, TNF- α levels were reduced by 67% and 37% with 2 or 5 μM CMC-2.24, and IL-6 levels by 9% with 5 μM CMC-2.24. IL-1β levels secreted by macrophages were reduced by 45% and 51% with 2 or 5 μM CMC-2.24.

Conclusions: Our lab has developed novel curcumin compounds with anti-inflammatory properties. The first generation included CMC-2.5, a compound with significant inhibitory effect on inflammatory cytokines and MMP-9 but was poorly soluble. The newer generation, CMC-2.24, is a derivative of CMC-2.5 with potent anti-inflammatory properties, solubility and greater efficacy in vivo. CMC-2.24 demonstrated greater therapeutic potential and may reduce tissue damage and bone loss in patients with periodontal disease or other inflammatory diseases.

Supported by NYSTAR grant #A43273 from CAT, SBU, Chem-Master Intl., Inc., and SB-Summer-Research-Fellowship-Program.