Curcumin is a plant-derived dietary spice ascribed various biological activities. Curcumin therapeutic applications have been studied in a variety of conditions, but not on periodontal disease. Periodontal disease is a chronic inflammatory condition initiated by an immune response to microorganisms of the dental biofilm. Experimental periodontal disease was induced in rats by injecting LPS in the gingival tissues on the palatal aspect of upper first molars (30 ug LPS, 3 times/week for 2 weeks). Curcumin was administered to rats daily via oral gavage at 30 and 100 mg/Kg. RT-qPCR and ELISA were used to determine the expression of IL-6, TNF-α and PGE2 synthase on the gingival tissues. The inflammatory status was evaluated by stereometric and descriptive analysis on H&E-stained sections, whereas modulation of p38 MAPK and NK-κB signaling was assessed by Western blot. Curcumin effectively inhibited cytokine gene expression at mRNA and protein levels, but NF-kB was inhibited only with the lower dose of curcumin, whereas p38 MAPK activation was not affected. Curcumin produced a significant reduction on the inflammatory infiltrate and increased collagen content and fibroblastic cell numbers. Curcumin potently inhibits innate immune responses associated with periodontal disease, suggesting a therapeutic potential in this chronic inflammatory condition.

Regulation of gene expression results from the activation of signaling pathways initiated by receptor-ligand binding of external antigens and also of cytokines produced by the host immune system. Understanding the signaling pathways relevant for a given condition may provide information useful for novel therapeutic approaches.

Curcumin is the active compound in the extract of Curcuma longa rhizomes with anti-inflammatory properties mediated by inhibition of intracellular signalling. SOCS and MAPKinases are involved in the signalling events controlling the expression of IL-6, TNF-α and PGE2, which have important roles on chronic inflammatory diseases. The aim was to assess if these pathways are involved in curcumin-mediated effects on LPS-induced expression of these cytokines in macrophages. RAW 264.7 murine macrophages were stimulated with Escherichia coli LPS in the presence and absence of non-cytotoxic concentrations of curcumin. Curcumin potently inhibited LPS-induced expression of IL-6, TNF-α and COX-2 mRNA and prevented LPS-induced inhibition of SOCS-1 and -3 expression and the inhibition of the activation of p38 MAPKinase by modulation of its nuclear translocation. In conclusion, curcumin potently inhibits expression of LPS-induced inflammatory cytokines in macrophages via mechanisms that involve modulation of expression and activity of SOCS-1 and SOCS-3 and of p38 MAPK.