Curcumin is not a ligand for peroxisome proliferator-activated receptor-γ

Curcumin, a compound found in the spice turmeric, has been shown to possess a number of beneficial biological activities exerted through a variety of different mechanisms. Some curcumin effects have been reported to involve activation of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma), but the concept that curcumin might be a PPAR-gamma ligand remains controversial. Results reported here demonstrate that, in contrast to the PPAR-gamma ligands ciglitazone and rosiglitazone, curcumin is inactive in five different reporter or DNA-binding assays, does not displace [H-3] rosiglitazone from the PPAR-gamma ligand-binding site, and does not induce PPAR-gamma-dependent differentiation of preadipocytes, while its ability to inhibit fibroblast-to-myofibroblast differentiation is not affected by any of four PPAR-gamma antagonists. These multiple lines of evidence conclusively demonstrate that curcumin is not a PPAR-gamma ligand and indicate the need for further investigation of the mechanisms through which the compound acts.