Peroxisome proliferator-activated receptor (PPAR)γ transcription factor has been implicated in anti-inflammatory response. Of the compounds tested, apigenin, chrysin, and kaempferol significantly stimulated PPARγ transcriptional activity in a transient reporter assay. In addition, these three flavonoids strongly enhanced the inhibition of inducible cyclooxygenase and inducible nitric oxide synthase promoter activities in lipopolysaccharide-activated macrophages which contain the PPARγ expression plasmids. However, these three flavonoids exhibited weak PPARγ agonist activities in an in vitro competitive binding assay. Limited protease digestion of PPARγ suggested these three flavonoids produced a conformational change in PPARγ and the conformation differs in the receptor bound to BRL49653 versus these three flavonoids. These results suggested that these three flavonoids might act as allosteric effectors and were able to bind to PPARγ and activate it, but its binding site might be different from the natural ligand BRL49653.
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