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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.

« Previous Next »
[1]
Jess T, Riis L, Vind I, et al. Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population-based study from Copenhagen, Denmark. Inflamm Bowel Dis 2007; 13(4): 481-9.
[http://dx.doi.org/10.1002/ibd.20036 ] [PMID: 17206705]
[2]
M’Koma AE. Inflammatory bowel disease: an expanding global health problem. Clin Med Insights Gastroenterol 2013; 6: 33-47.
[http://dx.doi.org/10.4137/CGast.S12731 ] [PMID: 24833941]
[3]
Fiocchi C. Inflammatory bowel disease pathogenesis: where are we? J Gastroenterol Hepatol 2015; 30(Suppl. 1): 12-8.
[http://dx.doi.org/10.1111/jgh.12751 ] [PMID: 25827798]
[4]
Felice C, Lewis A, Armuzzi A, Lindsay JO, Silver A. Review article: selective histone deacetylase isoforms as potential therapeutic targets in inflammatory bowel diseases. Aliment Pharmacol Ther 2015; 41(1): 26-38.
[http://dx.doi.org/10.1111/apt.13008 ] [PMID: 25367825]
[5]
Lu P-D, Zhao Y-H. Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines. Chin Med 2020; 15(1): 15.
[http://dx.doi.org/10.1186/s13020-020-0296-z ] [PMID: 32063999]
[6]
Glauben R, Batra A, Stroh T, et al. Histone deacetylases: novel targets for prevention of colitis-associated cancer in mice. Gut 2008; 57(5): 613-22.
[http://dx.doi.org/10.1136/gut.2007.134650 ] [PMID: 18194985]
[7]
Lee JW, Lee SM, Chun J. Novel Histone Deacetylase 6 Inhibitor CKD-506 inhibits NF-kappaB signaling in intestinal epithelial cells and macrophages and ameliorates acute and chronic murine Colitis. Inflamm Bowel Dis 2020; 26(6)
[8]
Reddy ND, Shoja MH, Biswas S, Nayak PG, Kumar N, Rao CM. An appraisal of cinnamyl sulfonamide hydroxamate derivatives (HDAC inhibitors) for anti-cancer, anti-angiogenic and anti-metastatic activities in human cancer cells. Chem Biol Interact 2016; 253: 112-24.
[http://dx.doi.org/10.1016/j.cbi.2016.05.008 ] [PMID: 27163855]
[9]
Reddy ND, Shoja MH, Jayashree BS, et al. In vitro and in vivo evaluation of novel cinnamyl sulfonamide hydroxamate derivative against colon adenocarcinoma. Chem Biol Interact 2015; 233: 81-94.
[http://dx.doi.org/10.1016/j.cbi.2015.03.015 ] [PMID: 25824412]
[10]
Figueiredo R D A, Ortega A C, Gonzalez Maldonado L A, et al. Perillyl alcohol has antibacterial effects and reduces ROS production in macrophages 2020.
[11]
Mathew G, Jacob A, Durgashivaprasad E, Reddy ND, Unnikrishnan MK. 6b,11b-Dihydroxy-6b,11b-dihydro-7H-indeno[1,2-b]naphtho[2,1-d]furan-7-one (DHFO), a small molecule targeting NF-κB, demonstrates therapeutic potential in immunopathogenic chronic inflammatory conditions. Int Immunopharmacol 2013; 15(1): 182-9.
[http://dx.doi.org/10.1016/j.intimp.2012.10.028 ] [PMID: 23159605]
[12]
Kondamudi P K, Kovelamudi H, Mathew G, Nayak P G, Rao C M, Shenoy R R. 2013.
[13]
Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-6.
[http://dx.doi.org/10.1016/S0076-6879(84)05016-3 ] [PMID: 6727660]
[14]
Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247(10): 3170-5.
[15]
Rai A, Gill M, Kinra M, et al. Catechin ameliorates depressive symptoms in Sprague Dawley rats subjected to chronic unpredictable mild stress by decreasing oxidative stress. Biomed Rep 2019; 11(2): 79-84.
[http://dx.doi.org/10.3892/br.2019.1226 ] [PMID: 31338194]
[16]
Hu M-L. Measurement of protein thiol groups and glutathione in plasma. Methods Enzymol 1994; 233: 380-5.
[http://dx.doi.org/10.1016/S0076-6879(94)33044-1 ] [PMID: 8015473]
[17]
Bryan NS, Grisham MB. Methods to detect nitric oxide and its metabolites in biological samples. Free Radic Biol Med 2007; 43(5): 645-57.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.04.026 ] [PMID: 17664129]
[18]
Shakespear MR, Halili MA, Irvine KM, Fairlie DP, Sweet MJ. Histone deacetylases as regulators of inflammation and immunity. Trends Immunol 2011; 32(7): 335-43.
[http://dx.doi.org/10.1016/j.it.2011.04.001 ] [PMID: 21570914]
[19]
Viatour P, Merville MP, Bours V, Chariot A. Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem Sci 2005; 30(1): 43-52.
[http://dx.doi.org/10.1016/j.tibs.2004.11.009 ] [PMID: 15653325]
[20]
Baldwin AS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 1996; 14: 649-83.
[http://dx.doi.org/10.1146/annurev.immunol.14.1.649 ] [PMID: 8717528]
[21]
aGuttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin AS Jr. 1999.; bKarin M, Cao Y, Greten FR, Li ZW. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2002; 2(4): 301-10.
[http://dx.doi.org/10.1038/nrc780 ] [PMID: 12001991]
[22]
de Souza HS, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol 2016; 13(1): 13-27.
[http://dx.doi.org/10.1038/nrgastro.2015.186 ] [PMID: 26627550]
[23]
Jiang X-L, Cui H-F. A new chronic ulcerative colitis model produced by combined methods in rats. World J Gastroenterol 2000; 6(5): 742-6.
[http://dx.doi.org/10.3748/wjg.v6.i5.742 ] [PMID: 11819686]
[24]
MacPherson BR, Pfeiffer CJ. Experimental production of diffuse colitis in rats. Digestion 1978; 17(2): 135-50.
[http://dx.doi.org/10.1159/000198104 ] [PMID: 627326]
[25]
Kiernan R, Brès V, Ng RW, et al. Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65. J Biol Chem 2003; 278(4): 2758-66.
[http://dx.doi.org/10.1074/jbc.M209572200 ] [PMID: 12419806]
[26]
Venkataranganna MV, Rafiq M, Gopumadhavan S, Peer G, Babu UV, Mitra SK. NCB-02 (standardized Curcumin preparation) protects dinitrochlorobenzene- induced colitis through down-regulation of NFkappa-B and iNOS. World J Gastroenterol 2007; 13(7): 1103-7.
[http://dx.doi.org/10.3748/wjg.v13.i7.1103 ] [PMID: 17373747]
[27]
de Zoeten EF, Wang L, Sai H, Dillmann WH, Hancock WW. Inhibition of HDAC9 increases T regulatory cell function and prevents colitis in mice. Gastroenterology 2010; 138(2): 583-94.
[http://dx.doi.org/10.1053/j.gastro.2009.10.037 ] [PMID: 19879272]
[28]
McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 1969; 244(22): 6049-55.
[29]
Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 2009; 30(1-2): 1-12.
[http://dx.doi.org/10.1016/j.mam.2008.08.006 ] [PMID: 18796312]
[30]
Kondamudi PK, Kovelamudi H, Nayak PG, Rao MC, Shenoy RR. Curcumin half analog modulates interleukin-6 and tumor necrosis factor-alpha in inflammatory bowel disease. Pharmacogn Mag 2015; 11(Suppl. 2): S296-302.
[http://dx.doi.org/10.4103/0973-1296.165991 ] [PMID: 26664018]
[31]
Dugani A, Dakhil B, Treesh S. Protective effect of the methanolic extract of malva parviflora l. leaves on acetic acid-induced ulcerative colitis in rats. Saudi J Gastroenterol 2016; 22(3): 226-33.
[http://dx.doi.org/10.4103/1319-3767.182459 ] [PMID: 27184642]

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