Propenone 유도체의 NF-kB 활성 억제 및 IL-8 유도에 의한 단핵구의 장 상피세포 부착 억제 효과

Inhibitory Effects of Propenone Derivatives on NF-kB activity and IL-8-Induced Monocyte Adhesion to Colon Epithelial Cells

In this study, we examined the inhibitory effects of propenone derivatives, 1,3-diphenyl-propenone (DPhP), 3- phenyl-1-thiophen-2-yl-propenone (PhT2P), 3-phenyl-1-thiophen-3-yl-propenone (PhT3P) and 1-furan-2-yl-3-phenyl-propenone (FPhP), on TNF-α-induced nuclear factor (NF)-κB activity and interleukin (IL)-8-induced monocyte adhesion to colon epithelial cells. 1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) that is previously reported as a NF-κB inhibitor suppressed TNF-α-induced monocyte-epithelial cell adhesion in a concentration-dependent manner. The propenone derivatives, DPhP, PhT2P, PhT3P, FPhP, also inhibited TNF-α-induced NF-κB activation in a similar degree to FPP-3. In a DPPH radical scavenging assay, none of the compounds showed DPPH radical scavenging activity, indicating that the inhibitory actions of the propenone derivatives on redox-sensitive NF-κB activity is not due to a simple free radical scavenging activity. In addition, the propenone derivatives also suppressed the IL-8-induced monocyte adhesion to colon epithelial cells. Furthermore, the effective concentrations of the propenone derivatives on both NF-κB activation as well as IL-8 induced monocyte-epithelial cell adhesion were 1000 times lower than 5-aminosalicylic acid (5-ASA), a clinically used drug for inflammatory bowel disease. These results suggest that the propenone derivatives may be a potential lead having a strong inhibitory activity against inflammatory cytokine-induced epithelial inflammation.