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Inhibition of LPS Induced iNOS, COX-2 and Cytokines Expression by $Genistein-4 through the $NF-{\kappa}B$ Inactivation in RAW 264.7 Cells  

Park, Seung-Jae (Department of pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University)
Kim, Ji-Yeon (Department of pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University)
Jang, Young-Pyo (Department of pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University)
Cho, Young-Wuk (Department of Physiology, College of Medicin,e Kyung-Hee University)
Ahn, Eun-Mi (Department of Herbal Food Science, Daegu Haany University)
Baek, Nam-In (Department of Life Science, Kyung-Hee University)
Lee, Kyung-Tae (Department of pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University)
Publication Information
Korean Journal of Pharmacognosy / v.38, no.4, 2007 , pp. 339-348 More about this Journal
Abstract
This study were designed to evaluate the anti-inflammatory effects of $genistein-4 (GRG) isolated from Sophora japonica (Leguminosae) on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin ($PGE_2$) production by RAW 264.7 cell line. GRG significantly inhibited the LPS-induced NO and $PGE_2$ production. Consistent with these observations, GRG reduced the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner. In addition, the release and the mRNA expression levels of tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ and interleukin-6 (IL-6) were also reduced by GRG. Moreover, GRG attenuated the LPS-induced activation of nuclear factor-kappa B ($NF-{\kappa}B$), a transcription factor necessary for pro-inflammatory mediators, iNOS, COX-2, $TNF-{\alpha}$ and IL-6 expression. These results suggest that the down regulation of iNOS, COX-2, $TNF-{\alpha}$, and IL-6 expression by GRG are achieved by the downregulation of $NF-{\kappa}B$ activity, and that is also responsible for its anti-inflammatory effects.
Keywords
$genistein-4; $NF-{\kappa}B$; LPS; Anti-inflammation; Sophora japonica;
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1 Willoughby, D. A. (1975) Human arthritis applied to animal models. Towards a better therapy. Ann. Rheum. Dis., 34: 471-478   DOI   ScienceOn
2 Lee, E. S., Ju, H. K., Moon, T. C., Lee, E., Jahng, Y., Lee S. H., Son, J. K., Baek, S. H. and Chang, H. W. (2004) Inhibition of nitric oxide and tumor necrosis factor$\alpha$ (TNF-$\alpha$) production by propenone compound through blockade of nuclear factor (NF)-$\kappa B$ activation in cultured murine macrophage. Biol. Pharm. Bull. 27: 617-620   DOI   ScienceOn
3 Funk, C. D., Frunk, L. B., Kennedy, M. E., Pong, A. S. and Fitzgerald, G. A. (1991) Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. FASEB J. 5: 2304-2312   DOI
4 Willeaume, V., Kruys, V., Mijatovic, T. and Huez, G. (1995) Tumor necrosis factor-alpha production induced by viruses and by lipopolysaccharides in macrophages: similarities and differences. J. Inflamm. 46: 1-12
5 Liu, S.F. and Malik, A.B. (2005) NF-$_KB$ activation as a pathological mechanism of septic shock and inflammation. Am. J. Physiol. Lung Cell Mol. Physiol. 290: L622-L645   DOI   ScienceOn
6 Harborne, J. B. and Wiliam, C. A. (2000) Advances in flavonoid research since 1992. Phytochemistry. 55: 481-504   DOI   ScienceOn
7 Seibert, K., Zhang, Y., Leahy, K., Hauser, S., Masferrer, J., Perkins, W., Lee, L. and Ksakson, P. (1994) Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc. Natl. Acad. Sci. U.S.A. 91: 12013-12017
8 Kim, H. J., Kim, M. K., Shim, J. G., Yeom, S. H., Kwon, S. H. and Lee, M. W. (2004) Anti-oxidative phenolic compounds from Sophorae fructus. Nat. Prod. Sci. 10: 330-334
9 Moncada, S., Palmer, R. M. and Higgs, E. A. (1991) Nitric oxide:physiology. Pathophysiology, and pharmacology. Pharmacol. Rev. 43: 109-142
10 Scott, M. G. and Hancock, R. E. (2000) Cationic antimicrobial peptides and their multifunctional role in the immune system. Crit. Rev. Immunol. 20: 407-431
11 Wenzel, U., Kuntz, S., Brendel, M. D. and Daniel, H. (2000) Dietary flavone is a potent apoptosis inducer in human colon carcinoma cells. Cancer Res. 60: 3823-3831
12 Weisz, A., Cicatiello, I. and Esumi, H. (1996) Regulation of the mouse inducible-type nitric oxide synthase gene promoter by interferon-gamma, bacterical lipopolysaccharide and NG-monomethyl-L-arginene. Biochem. J. 316: 209-215   DOI
13 Michael, E. E. (1986) Manual of cultivated broad-leaved tress & shrubs. Volume, Timber Press, Protland, Oregon. pp. 325-327
14 Iontcheva, I., Amar, S., Zawawi, K.H., Kantarci, A. and Van Dyke, T.E. (2004) Role for moesin in lipopolysaccharidestimulated signal transduction. Infect Immun. 72: 2312-2320   DOI
15 O'Neill, G. and Hutchinson, A.F. (1993) Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett. 330: 156-160
16 Iontcheva, I., Amar, S., Zawawi, K.H., Kantarci, A. and Van Dyke, T.E. (2004). Role for moesin in lipopolysaccharidestimulated signal transduction. Infect Immun. 72: 2312-2320   DOI
17 MukIS, N., Ishikawa, Y., Ikeda, N., Fujioka, N., Watanabe, S. and Kuno, K. (1996) Novel insight into molecular mechanism of endotoxin shock; biochemical analysis of LPS receptor signaling in a cell-free system targeting NF-kapperB and regulation of cytokine production/action through beta2 integrin in vivo. J. Leukoc. Biol. 59: 145-151   DOI
18 Vane, J. A. (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat. New. Biol. 23: 232-235
19 McCartney-Francis, N., Allen, J. B., Mizel, D. E., Albina, J. E., Xie, Q. W., Nathan, C. F. and Wahl, S. M. (1993) Suppression of arthritis by an inhibitor of nitic oxide synthase. J. Exp. Med. 178: 749-754   DOI   ScienceOn
20 Van Snick, J. (1990) IL-6: an overview. Annu. Rev. Immunol. 8: 253-278   DOI   ScienceOn
21 Feldmann, M., Brennan, F. M. and Maini, R. N. (1996) Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 14: 397-440   DOI   ScienceOn
22 Surh, Y.J., Chun, K.S., Cha, H.H., Han, S.S., Keum, Y.S., Park, K.K. and Lee, S.S. (2001) Molecular mechanism underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat. Res. 480-481: 243-268   DOI
23 Axtelle, T. and Pribble, J. (2001) IC14, a CD14 specific monoclonal antibody is a potential treatment for patients with severe sepsis. J. Endotoxin. Res. 7: 310-314   DOI
24 Nathan, C. (1992) Nitric oxide as a secretory product of mammalian cells. FASEB J. 6: 3051-3064   DOI
25 Stuehr, H. H. J., Kwon, N. S., Weise, M. and Nathan, C. (1991) Purification of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN- containing flavoprotein. Proc. Natl. Sci. USA. 88: 7773-7777
26 Nature, and Medicine study association of Korea, Life-Chinese Medicine Folk Medicine. DongBu-MunHwaSa. pp. 21 (1985)
27 Karin, M. and Ben-Neriah, Y. (2000) Phosphorylation meets ubiquitination: the control of NF-B activity. Annu. Rev. Immunol. 18: 621-663   DOI   ScienceOn
28 Masferrer, J., Zweifel B. S., Manning, P. T., Hauser, S. D., Leahy, K. M., Smith, W. G., Isacson, P. C. and Seibert, K. (1994) Selective inhibition of inducible cyclooxygenase 2 in vivo is anti-inflammatory and nonulcerogenic. Proc. Natl. Acad. Sci. U.S.A. 91: 3228-3232
29 Lazarov, S., Balutsov, M. and lanev, E. (2000) The role of bacterial endotoxins, receptors and cytokines in the pathogenisis of septic(endotoxin) shock. Vutr. Boles. 32: 33-40
30 Jun, M. R., Hong, J. G., Jeong, W. S. and Ho, C. T. (2005) Suppression of arachidonic acid metabolism and nitric oxide formation by kudzu isoflavones in murine macrophages. Mol. Nutr. Food res. 49: 1154-1159   DOI   ScienceOn
31 Gomez, P.F., Pillinger, M.H., Attur, M., Marjanovic, N., Dave, M., Park, J., Bingham, C.O., Al-Mussawir, H. and Abramson, S.B. (2005). Resolution of inflammation: prostaglandin $E_2$ dissociates nuclear trafficking of individual NFkappa B subunits (p65, p50) in stimulated rheumatoid synovial fibroblasts. J. Immunol. 175: 6924-6930   DOI
32 Verdrengh, M., Jonsson, I. M., Holmdahl, R. and Tarkowski, A. (2003) genistein as an anti-inflammatory agent. Inflamm. Res. 52: 341-346   DOI