ABC> Vol.3 No.6, December 2013
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Molecular basis of the anti-inflammatory potential of a diarylheptanoid in murine macrophage RAW 264.7 cells

DownloadDownload as PDF (Size:912KB) PP. 541-548   DOI: 10.4236/abc.2013.36061

ABSTRACT

Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory disorders. In this study, we examined the molecular basis of the anti-inflammatory potential of a diarylheptonoid (DAH) isolated from Alpinia officinarum hexane extract (AOHE) with special emphasis on their ability to modulate the nuclear factor-κB (NF-кB) signaling involved in the inflammatory response. Measurement of Nitrite by Griess reaction which revealed the effect of DAH in RAW 264.7 macrophages showed an inhibition in the nitric oxide production through the suppression of inducible nitric oxide synthase (iNOS) gene level expression. NF-кB reporter gene assay suggests inhibition of NF-кB transcriptional activity, thus inhibiting LPS-induced phosphorylation and degradation of IкBα and a downregulation of NF-кB protein expression confirms the immunomodulatory effect of DAH. Furthermore, downregulation in the gene level expression of NF-кB signaling markers such as IL-1β, TNF-α and COX-2 suggests the anti-inflammatory potential of DAH via inhibition of NF-кB activation.

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Cite this paper

Rajaganapathy, B. , Thirugnanam, K. , Shanmuganathan, M. , Singaravelu, A. and Subadhra, L. (2013) Molecular basis of the anti-inflammatory potential of a diarylheptanoid in murine macrophage RAW 264.7 cells. Advances in Biological Chemistry, 3, 541-548. doi: 10.4236/abc.2013.36061.

References

[1] Shin, K.M., Kim, Y.H., Park, W.S., Kang, I., Ha, J., Choi, J.W., Park, H.J. and Lee, K.T. (2004) Inhibition of methanol extract from the fruits of Kochiascoparia on lipopolysaccharide-induced nitric oxide, prostaglandin E2, and tumor necrosis factor-alpha production from murine macrophage RAW 264.7 cells. Biological & Pharmaceutical Bulletin, 27, 538-543.
http://dx.doi.org/10.1248/bpb.27.538
[2] Kroncke, K.D., Fehsel, K. and Kolb-Bachofen, V. (1998) Inducible nitric oxide synthase in human diseases. Clinical & Experimental Immunology, 113, 147-156.
http://dx.doi.org/10.1046/j.1365-2249.1998.00648.x
[3] Laskin, D.L. and Pendino, K.J. (1995) Macrophages and inflammatory mediators in tissue injury. Annual Review of Pharmacology and Toxicology, 35, 655-677.
http://dx.doi.org/10.1146/annurev.pa.35.040195.003255
[4] Baeuerle, P.A. (1998) IκB-NF-κB structures: At the interface of inflammation control. Cell, 95, 729-731.
http://dx.doi.org/10.1016/S0092-8674(00)81694-3
[5] Brown, K., Gerberger, S., Carlson, L., Franzoso, G. and Siebenlist, U. (1995) Control of IκB-alpha proteolysis by site-specific, signal-induced phosphorylation. Science, 267, 1485-1488. http://dx.doi.org/10.1126/science.7878466
[6] Didonato, J., Mercurio, F., Rosette, C., Wu, L.I., Suyang, H., Ghosh, S. and Karin, M. (1996) Mapping of the inducible IκB phosphorylation sites that signal its ubiquitination and degradation. Molecular and Cellular Biology, 4, 1295-1304.
[7] Bonizzi, G. and Karin, M. (2004) The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends in Immunology, 25, 280-288.
http://dx.doi.org/10.1016/j.it.2004.03.008
[8] Jirik, F.R., Podor, T.J., Hirano, T., Kishimoto, T., Loskutoff, D.J., Carson, D.A. and Lotz, M. (1989) Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. Journal of Immunology, 142, 144-147.
[9] Giuliano, F. and Warner, T.D. (2002) Origins of prostaglandin E2: Involvements of cyclooxygenase (COX)-1 and COX-2 in human and rat systems. Journal of Pharmacology and Experimental Therapeutics, 303, 1001-1006. http://dx.doi.org/10.1124/jpet.102.041244
[10] Tak, P.P. and Firestein, G.S. (2001) NF-κB: A key role in inflammatory diseases. The Journal of Clinical Investigation, 107, 7-11. http://dx.doi.org/10.1172/JCI11830
[11] Guha, M. and Mackman, N. (2001) LPS induction of gene expression in human monocytes. Cell Signal, 13, 85-94. http://dx.doi.org/10.1016/S0898-6568(00)00149-2
[12] Subramanian, K., Selvakkumar, C., Vinaykumar, K.S., Goswami, N., Meenakshisundaram, S., Balakrishnan, A. and Lakshmi, B.S. (2009) Tackling multiple antibiotic resistance in enteropathogenic Escherichia coli (EPEC) clinical isolates: A diarylheptanoid from Alpiniaofficinarum shows promising antibacterial and immunomodulatory activity against EPEC and its lipopolysaccharide-induced inflammation. International Journal of Antimicrobial Agents, 33, 244-250.
http://dx.doi.org/10.1016/j.ijantimicag.2008.08.032
[13] Gayathri, B., Manjula, N., Vinaykumar, K.S., Lakshmi, B.S. and Balakrishnan, A. (2007) Pure compound from Boswelliaserrata extractexhibits anti-inflammatory property in human PBMCs and mousemacrophages through inhibition of TNF-α, IL-1α, NO and MAP kinases. International Immunopharmacology, 7, 473-482.
http://dx.doi.org/10.1016/j.intimp.2006.12.003
[14] Kim, J.Y., Jung, K.S. and Jeong, H.G. (2004) Suppressive effects of the kahweol and cafestolon cyclooxygenase-2 expression in macrophages. FEBS Letters, 569, 321-326. http://dx.doi.org/10.1016/j.febslet.2004.05.070
[15] Rosalbasacca, C., Cuff, A. and Nancy, H.R. (1997) Mediators of inflammation. Current Opinion in Immunology, 9, 851-857.
[16] Karin, M. and Ben Neriah, Y. (2000) Phosphorylation meets ubiquitination: the control of NF-κB activity. Annual Review of Immunology, 18, 621-663.
http://dx.doi.org/10.1146/annurev.immunol.18.1.621
[17] Epinat, J.C. and Gilmore, T.D. (1999) Diverse agents act at multiple levels to inhibit the Rel/NF-κB signal transduction pathway. Oncogene, 18, 6896-6909.
http://dx.doi.org/10.1038/sj.onc.1203218
[18] Madhavan, P.N., Supriya, M., Jessica, L.R., Ravikumar, A., Harikrishnan, N., Stanley, A.S. and Chithan, K. (2006) The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-κB System. Clinical and Vaccine Immunology, 13, 319-328.
http://dx.doi.org/10.1128/CVI.13.3.319-328.2006
[19] Jobin, C. (1999) Curcumin blocks cytokine-mediated NF-κB activation and proinflammatory gene expression by inhibiting inhibitory factor IκB kinase activity. Journal of Immunology, 163, 3474-3483.
[20] Korhonen, R., Lahti, A., Kankaanranta, H. and Moilanen, E. (2005) Nitric oxide production and signaling in inflammation. Current Drug Targets: Inflammation & Allergy, 4, 471-479. http://dx.doi.org/10.2174/1568010054526359
[21] Haefner, B. (2002) NF-κB: Arresting a major culprit in cancer. Drug Discovery Today, 7, 653-663.
http://dx.doi.org/10.1016/S1359-6446(02)02309-7
[22] Sizemore, N., Lerner, N., Dombrowski, N., Sakurai, H. and Stark, G.R. (2002) Distinct roles of the IkB kinase α and β subunits in liberating nuclear factor kB (NF-kB) from IkB and in phosphorylating the p65 subunit of NF-kB. Journal of Biological Chemistry, 277, 3863-3869.
http://dx.doi.org/10.1074/jbc.M110572200
[23] Gayathri, B., Lakshmi, J., Arun, B. and Baddireddi Subhadra, L. (2010) Molecular basis of the anti-inflammatory property exhibited by Cyclo-Pentano Phenanthrenol isolated from Lippianodiflora. Immunological Investigations, 39, 713-739.
http://dx.doi.org/10.3109/08820139.2010.493190
[24] Angela, S., Sumikotanaka, T., Hidetakamiyoshi, T., Masaki, S., Keisuke, K. and Takahisa, S. (1997) Pathophysiological role of nitric oxide in rat experimental colitis. International Journal of Immunopharmacology, 19, 669-676.
[25] Tak, P.P. and Firestein, G.S. (2001) NF-κB: A key role in inflammatory diseases. Journal of Clinical Investigation, 107, 7-11. http://dx.doi.org/10.1172/JCI11830
[26] Dixon, D.A. (2004) Dysregulated post-transcriptional control of COX-2 gene expression in cancer. Current Pharmaceutical Design, 10, 635-646.
http://dx.doi.org/10.2174/1381612043453171

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