Cinnamyl Sulfonamide Hydroxamate Derivatives Inhibited LPS-Stimulated NF-kB Expression in RAW 264.7 Cells in In Vitro and Mitigated Experimental Colitis in Wistar Rats in In Vivo

BACKGROUND: Histone deacetylase (HDAC) inhibition has been found to be effective in the treatment of inflammatory bowel disease. Previous studies reported that Cinnamyl sulfonamide hydroxamate derivatives possessed nonselective HDAC inhibition. OBJECTIVE: The present study was designed to screen three selected Cinnamyl sulfonamide hydroxamate derivatives, NMJ1, NMJ-2 and NMJ3 for in vitro anti-inflammatory response by assessing the expression of pNF-κB in lipopolysaccharide (LPS)-induced inflammatory changes on RAW 264.7 cells and in vivo anti-inflammatory response in acetic acid (AA) and 2.4-dinitrochlorobenzene (DNCB)-induced colitis models in Wistar rats. METHOD: AA-induced colitis was produced in Wistar rats by intra-colonic administration of 1 ml AA. DNCB-induced colitis was produced by spraying 250 µL DNCB in acetone (20g/L) on the nape of the rats for 14 days followed by the intracolonic administration on day 15. Drugs were administered for three days after the induction of colitis. RESULTS: In vitro anti-inflammatory effect observed by NMJ1 and NMJ2 by a significant decrease in pNF-κB overexpression-induced by LPS. Similar effect was observed in anti-colitis responses by NMJ2 in both models by reversing the colitis-induced changes in length, weight, antioxidant profile and histopathology of the colon. CONCLUSION: NMJ2 was found to be most effective among the tested compounds as an anti-inflammatory agent in both in vitro and in vivo inflammatory studies.