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Inhibition of LPS induced iNOS, COX-2 and cytokines expression by kaempferol-3-O-${\beta}$-D-sophoroside through the $NF{-\kappa}B$ inactivation in RAW 264.7 cells  

Park, Seung-Jae (Department of pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University)
Shin, Ji-Sun (Department of pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University)
Cho, Woong (Department of pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University)
Cho, Young-Wuk (Department of physiology, College of Medicine, 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.39, no.2, 2008 , pp. 95-103 More about this Journal
Abstract
In the present study, we investigated the anti-inflammatory effects by kaempferol-3-O-${\beta}$-D-sophoroside (KS) isolated from Sophora japonica (Leguminosae) on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin ($PGE_2$) production by RAW 264.7 cell line compared with kaempferol. KS significantly inhibited the LPS-induced NO and $PGE_2$ production. Consistent with these observations, KS 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 KS. Moreover, KS 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 KS are achieved by the downregulation of $NF{-\kappa}B$ activity, and that is also responsible for its anti-inflammatory effects.
Keywords
Kaempferol-3-O-${\beta}$-D-sophoroside$NF{-\kappa}B$; 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 Liu, S.F. and Malik, A.B. (2005) $NF-_{\kappa}B$ activation as a pathological mechanism of septic shock and inflammation. Am. J. Physiol. Lung Cell Mol. Physiol. 290: L622-L645   DOI   ScienceOn
3 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
4 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
5 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
6 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
7 Du, J., He, Z. D., Jiang, R. W., Ye, W. C., Xu, H. X., and But, P. P. (2003) Antiviral flavonoids from the root bark of Morus alba L. Phytochemistry. 62: 1235-1238   DOI   ScienceOn
8 Garcia-Mediabilla, V., Crespo, I., Collado, P. S., Esteller, A., Sanchez-Campos, S., Tunon, M. J., and Gonzalez-Gallego, J. (2007) The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and downregulation of the nuclear factor kappaB pathway in Chang Liver cells. Eur. J. Pharmacol. 28: 221-229
9 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
10 Nature, and Medicine study association of Korea, Life-Chinese Medicine 'Folk Medicine. DongBu-MunHwaSa. pp. 21 (1985)
11 Song, E. K., Hur, H., and Han, M. K. (2003) Epigallocatechin gallate prevents autoimmune diabetes induced by multiple low doses of streptozotocin in mice. Arch. Pharm. Res. 26: 559-563   DOI   ScienceOn
12 Kashiwada, Y., Nonada, G., Nishioka, I., Chang, J. J., and Lee, K. H. (1992) Antitumor agents, 129. tannins and related compounds as selective cytotoxic agents. J. Nat. Prod. 55: 1033-1043   DOI
13 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
14 Shen. S. C., Ko, C. H., Hsu, K. C., and Chen, Y. C. (2004) 3-OH flavone inhibition of epidermal growth factor-induced proliferation through blocking prostaglandin E2 production. Int. J. Cancer. 108: 502-510   DOI   ScienceOn
15 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
16 Theoharides, T. C., Alexandrakis, M., Kempuraj, D., and Lytinas, M. (2001) Anti-inflammatory actions of flavonoids and structural requirements for new design. Int. J. Immunopathol. Pharmacol. 14: 119-127
17 Kowalski, J., Samojedny, A., Paul, M., Pietsz, G., and Wilczok, T. (2005) Effect of apigenin, kaempferol and resveratrol on the expression of interleukin-1beta and tumor necrosis factor-alpha genes in J774.2 macrophages. Pharmacol. Rep. 57: 390-394
18 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
19 Waffo-Teguo, P., Hawthorne, M. E., Cuendet, M., Merillon, J. M., Kinghorn, A. D., Pezzuto, J. M., and Mehta, R. G. (2001) Potential cancer chemopreventive activities of wine stilbenoids and flavans extracted from grape (Vitis vinifera) cell cultures. Nutr. Cancer. 40: 173-179   DOI   ScienceOn
20 Michael, E. E. (1986) Manual of cultivated broad-leaved tress & shrubs. Volume, Timber Press, Protland, Oregon. pp. 325-327
21 Karin, M. and Ben-Neriah, Y. (2000) Phosphorylation meets ubiquitination: the control of NF-B activity. Annu. Rev. Immunol. 18: 621-663   DOI   ScienceOn
22 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-a (TNF-a) production by propenone compound through blockade of nuclear factor (NF)-eB activation in cultured murine macrophage. Biol. Pharm. Bull. 27: 617-620   DOI   ScienceOn
23 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
24 Yu, H. N., Yin, J. J., and Shen, S. R. (2004) Growth inhibition of prostate cancer cells by epigallocatechin gallate in the presence of $Cu^{++}$. J. Agric. Food Chem. 52: 462-466   DOI   ScienceOn
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 Feldmann, M., Brennan, F. M. and Maini, R. N. (1996) Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 14: 397-440   DOI   ScienceOn
27 Kashiwada, Y., Nonada, G., Nishioka, I., Ballas, L. M., Jiang, J. B., Janzeng, W. P., and Lee, K. H. (1992) Tannins as selective inhibitors of protein kinase C. Bioorg. Med. Chem. Letters. 2: 239-244   DOI   ScienceOn
28 Harborne, J. B. and Wiliam, C. A. (2000) Advances in flavonoid research since 1992. Phytochemistry. 55: 481-504   DOI   ScienceOn
29 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
30 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
31 Park, S. J., Kim, J. Y., Jang, Y. P., Cho, Y. W., Ahn, E. M., Beek, N. I., Lee, K. T. (2007) Inhibition of LPS induced iNOS, COX-2 and cytokines expression by $genistein-4 through the $NF-_{\kappa}B$ inactication in RAW 264.7 cells. Kor. J. Pharmacogn. 38: 339-348   과학기술학회마을
32 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