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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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General Research Article

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

Author(s): Mit Joshi, Neetinkumar D. Reddy, Nitesh Kumar*, Suhani Sumalatha and Mallikarjuna Rao Chamallamudi*

Volume 26, Issue 38, 2020

Page: [4934 - 4943] Pages: 10

DOI: 10.2174/1381612826666200625101442

Price: $65

Abstract

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-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. DNCBinduced 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 was observed by NMJ1 and NMJ2 through a significant decrease in pNF-κB 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.

Keywords: Inflammatory bowel disease, cinnamyl sulfonamide hydroxamate derivatives, Sulphasalazine, 2, 4-Dinitrochlorobenzene-induced colitis, acetic acid-induced colitis, HDAC inhibitors, anti-oxidant, NF-κB.

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