Therapeutic effect of curcumin, a plant polyphenol extracted from curcuma longae, in fibroblasts from patients with graves’ orbitopathy

PURPOSE. We examined the therapeutic effect of nontoxic concentrations of curcumin, a plant polyphenol extracted from Curcuma longae, in primary cultures of orbital fibroblasts from Graves’ orbitopathy (GO). METHODS. The effect of curcumin on interleukin (IL)-1b induced–proinflammatory cytokine production was determined using quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis. Adipogenic differentiation was identified using Oil-Red O staining, and levels of peroxisome proliferator activator c (PPARc) and CCAATenhancer-binding proteins (C/EBP) a/b were determined by Western blot analyses. Antioxidant activity was measured using an oxidant-sensitive fluorescent probe to detect intracellular reactive oxygen species (ROS) generated in response to hydrogen peroxide (H₂O₂) and cigarette smoke extract (CSE). RESULTS. Treatment with curcumin resulted in a dose- and time-dependent decrease in IL-1b–induced synthesis of inflammatory cytokines, including IL-6, IL-8, MCP-1, and ICAM-1 at both mRNA and protein levels. Decrease in lipid droplets and expression of PPARc and c/EBPa/b were noted in fibroblasts treated with curcumin during adipose differentiation. CSE- or H₂O₂induced ROS synthesis was significantly lower in curcumin-treated fibroblasts in comparison with the control. Curcumin significantly suppressed IL-1b–induced phosphorylated extracellular signal-regulated kinase, Akt, c-Jun NH(2)-terminal kinase, and nuclear factor j-light-chain-enhancer of activated B cells, p65 proteins and stimulated b-catenin translocation into nucleus during adipogenesis. CONCLUSIONS. Curcumin inhibits proinflammatory cytokine production, ROS synthesis, and adipogenesis in orbital fibroblasts of GO patients in vitro possibly related to multiple proinflammatory signaling molecules and b-catenin pathway. The results of the study support potential use of the curcumin in the treatment of GO.