Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 26, Issue 38, Pages 4934-4943Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612826666200625101442
Keywords
Inflammatory bowel disease; cinnamyl sulfonamide hydroxamate derivatives; Sulphasalazine; 2,4-Dinitrochlorobenzene-induced colitis; acetic acid-induced colitis; HDAC inhibitors; anti-oxidant; NF-kappa B
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Funding
- Science and Engineering Research Board (SERB) Government of India [SR/SO/HS-0282/2012]
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Background: Histone deacetylase (HDAC) inhibition has been found to be effective in the treatment of inflammatory bowel disease. Previous studies have reported that Cinnamyl sulfonamide hydroxamate derivatives possess non-selective HDAC inhibition. Objective: The present study was designed to screen three selected Cinnamyl sulfonamide hydroxamate derivatives, NMJ-1, NMJ-2, and NMJ3, for in vitro anti-inflammatory response by assessing the expression of pNF-kappa B 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 mu L 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 was observed by NMJ1 and NMJ2 through a significant decrease in pNF-kappa B overexpression-induced by LPS. Similar effect was observed in anti-colitis response by NMJ2 in both models by reversing the colitis-induced changes in length, weight, anti-oxidant 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.
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