The anti-inflammatory activities of a prepared isoegomaketone 3a and its derivatives 3b-3f were evaluated in RAW 264.7 cells. Among these, the compound 3d was displayed the most potent inhibitory activities against production of nitric oxide, monocyte chemoattractant protein-1 and interleukin-6. Based on these results, the abilities of compounds 3a-3f to modulate NF-${kappa}B$ and AP-1-mediated gene transcription using a luciferase reporter assay were investigated. The transcriptional activities of NF-${kappa}B$ and AP-1 decreased when pretreated with 3a-3f. Interestingly, at $10{mu}M$, compound 3d markedly suppressed the lipopolysaccharide-induced NF-${kappa}B$ and activator protein-1 DNA binding activities. Some preliminary structure-activity relationships were proposed that may provide a direction for further study.