Propenone derivatives inhibit TNF‐α‐ and TNBS‐induced intestinal inflammation in vitro and in vivo

Abstract

In inflammatory bowel disease (IBD), colon epithelial cells increased the expression of a variety of inflammatory mediators, cell adhesion molecules and chemokines. In this study, we examined the effect of novel 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 inflammatory cytokine‐induced responses in HT‐29 human colon epithelial cells. We found that DPhP most effectively blocked TNF‐α‐induced adhesion of U937 monocytes to HT‐29 cells, which is an initial step of colon inflammation. DPhP inhibited the expression of IL‐8, MCP‐1 and ICAM‐1 in a concentration‐dependent manner. When HT‐29 cells were transfected with NF‐κB‐Luc plasmid, DPhP significantly inhibited TNF‐α‐induced luciferase activity. In trinitrobenzene sulfonic acid (TNBS)‐induced rat colitis model, DPhP dose‐dependently protected from the TNBS‐induced weight loss, myeloperoxidase activity increase. At the same time, DPhP suppressed the TNBS‐induced mRNA expression of IL‐8, IL‐6 and MCP‐1. Taken together, the results suggest that DPhP may be a potential candidate to suppress the colon inflammation via inhibition of major pro‐inflammatory cytokines involved in intestinal inflammation.