Cinnamaldehyde inhibits the tumor necrosis factor‐£\‐induced expression of adhesion molecules in endothelial cells by suppressing NF‐£eB activation

The production of adhesion molecules and subsequent attachment of leukocytes to endothelial cells (ECs) are critical early events in atherogenesis. In this study, we have examined the effect of cinnamaldehyde on cytokine‐induced monocyte/ECs interactions. We find that these compounds inhibit the adhesion of TNFα‐induced monocytes to endothelial cells and suppress the expression of the adhesion molecules. In TNFα‐treated ECs, NF‐κB was also abolished. Interestingly, cinnamaldehyde exerts its anti‐inflammatory effects by blocking the degradation of the inhibitory protein IκB‐α, but only in short term pretreatments, whereas it does so via the induction of Nrf2‐related genes, including heme‐oxygenase‐1 (HO‐1), over long term pretreatments. Treating ECs with zinc protoporphyrin, HO‐1 inhibitor, partially blocks the anti‐inflammatory effects of cinnamaldehyde. We also found that cinnamaldehyde can upregulate Nrf2 in nuclear extracts, and can increase ARE‐luciferase activity. Moreover, cinnamaldehyde increases cellular GSH levels after 9 hours exposure. Hence, our present findings indicate that cinnamaldehyde suppresses TNF‐induced singling pathways via distinct mechanisms that are activated by different pretreatment periods.