Anti-inflammatory Effects of a P-coumaric Acid and Kojic Acid Derivative in LPS-stimulated RAW264.7 Macrophage Cells

Numerous derivatives of natural substances have been synthesized to improve their functionality while avoiding the risk of side effects. Both kojic acid and pcoumaric acid are natural products with known antiinflammatory properties. In this study, we synthesized an ester derivative of kojic acid and p-coumaric acid, 5- Hydroxy-4-oxo-4H-pyran-2-yl-methyl (E)-3-(3-hydroxyphenyl) acrylate (compound 3), and evaluated its synergistic anti-inflammatory effects. To determine the anti-inflammatory activity of compound 3 in lipopolysaccharide (LPS)- stimulated RAW264.7 macrophage cells, the degree of inhibition of nitric oxide (NO) production, a typical inflammatory mediator, was measured. Kojic acid and pcoumaric acid individually showed no inhibition at 100 μM, whereas compound 3 showed 60% inhibition at the same concentration. Furthermore, we investigated the change in activity of NF-κB, a key transcription factor in inflammatory response, using RAW264.7 Gaussia luciferase reporter cells. Compound 3 suppressed the activation of NF-κB by approximately 32% at 25 μM. However, 200 μM of kojic acid and p-coumaric acid inhibited NF-κB activation by 20% and 15%, respectively. Taken together, our data suggest that the anti-inflammatory effect of compound 3 is due, at least in part, to the inhibition of NF-κB activation.