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http://dx.doi.org/10.4110/in.2012.12.5.181

Immunomodulatory Effects of Dioscoreae Rhizome Against Inflammation through Suppressed Production of Cytokines Via Inhibition of the NF-${\kappa}B$ Pathway  

Kim, Seulah (College of Pharmacy, Sahmyook University)
Shin, Seulmee (College of Pharmacy, Sahmyook University)
Hyun, Bobae (College of Pharmacy, Sahmyook University)
Kong, Hyunseok (College of Pharmacy, Sahmyook University)
Han, Shinha (College of Pharmacy, Sahmyook University)
Lee, Aeri (College of Pharmacy, Sahmyook University)
Lee, Seungjeong (College of Pharmacy, Chungbuk University)
Kim, Kyungjae (College of Pharmacy, Sahmyook University)
Publication Information
IMMUNE NETWORK / v.12, no.5, 2012 , pp. 181-188 More about this Journal
Abstract
Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-${\kappa}B$, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-${\kappa}B$-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.
Keywords
Dioscoreae Rhizoma; Anti-inflammatory; Inflammatory cytokines; Immunomodulatory agent;
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1 Lee, G. I., J. Y. Ha, K. R. Min, H. Nakagawa, S. Tsurufuji, I. M. Chang, and Y. Kim. 1995. Inhibitory effects of oriental herbal medicines on IL-8 induction in lipopolysaccharideactivated rat macrophages. Planta. Med. 61: 26-30.
2 Laskin, D. L. and K. J. Pendino. 1995. Macrophages and inflammatory mediators in tissue injury. Annu. Rev. Pharmacol. Toxicol. 35: 655-677.
3 Furchgott, R., P. Cherry, J. Zawadzki, and D. Jothianandan. 1984. Endothelial cells as mediators of vasodilation of arteries. J. Cardiovasc. Pharmacol. 6: S336-343.
4 Wei, X., I. Charles, A. Smith, J. Ure, G. Feng, and H. Huang. 1995. Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375: 408-4011.
5 Ahmad, N., L. C. Chen, M. A. Gordon, J. D. Laskin, and D. L. Laskin. 2002. Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia. J. Leukoc. Biol. 71: 1005-1011.
6 Li, Q. and I. M. Verma. 2002. NFkappa B regulation in the immune system. Nat. Rev. Immunol. 2: 725-734.
7 Richmond, A. 2002. NF-kappa B, chemokine gene transcription and tumour growth. Nat. Rev. Immunol. 2: 664-674.
8 Lee, S., S. Shin, H. Kim, S. Han, K. Kim, J. Kwon, J. H. Kwak, C. K. Lee, N. J. Ha, D. Yim, and K. Kim. 2011. Antipinflammatory function of arctiin by inhibiting COX-2 expression via NF-kappaB pathways. Inflammation 8: 16.
9 Karin, M. and Y. Ben-Neriah. 2000. Phosphorylation meets ubiquitination: The control of NF-kappa B activity. Annu. Rev. Immunol. 18: 621-663.
10 Stuehr, D. J. and C. F. Nathan. 1989. Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J. Exp. Med. 169: 1543-1555.
11 Duncan, B. B., M. I. Schmidt, J. S. Pankow, C. M. Ballantyne, D. Couper, A. Vigo, R. Hoogeveen, A. R. Folsom, and G. Heiss; Atherosclerosis Risk in Communities Study. 2003. Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes 52: 1799-1805.
12 Jacobs, M., M. M. van Greevenbroek, C. J. van der Kallen, I. Ferreira, E. E. Blaak, E. J. Feskens, E. H. Jansen, C. G. Schalkwijk, and C. D. Stehouwer. 2009. Low-grade inflammation can partly explain the association between the metabolic syndrome and either coronary artery disease or severity of peripheral arterial disease: the CODAM study. Eur. J. Clin. Invest. 39: 437-444.
13 Vane, J. R., J. A. Mitchell, I. Appleton, A. Tomlinson, D. Bishop-Bailey, J. Croxtall, and D. A. Willoughby. 1994. Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation. Proc. Natl. Acad. Sci. USA 91: 2046-2050.
14 Lee, T. H., H. B. Kwak, H. H. Kim, Z. H. Lee, D. K. Chung, N. I. Baek, and J. Kim. 2007. Methanol extracts of Stewartia koreana inhibit cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) gene expression by blocking NF-kappaB transactivation in LPS-activated RAW 264.7 cells. Mol. Cells 23: 398-404.
15 Nathan, C. 1997. Inducible nitric oxide synthase: what difference does it make? J. Clin. Invest. 100: 2417-2423.
16 Bogdan, C. 2001. Nitric oxide and the immune response. Nat. Immunol. 2: 907-916.
17 Vila-del Sol, V. and M. Fresno. 2005. Involvement of TNF and NF-kappa B in the transcriptional control of cyclooxygenase- 2 expression by IFN-gamma in macrophages. J. Immunol. 174: 2825-2833.
18 Lind, L. 2003. Circulating markers of inflammation and atherosclerosis. Atherosclerosis 169: 203-214.
19 Tilg, H., A. Wilmer, W. Vogel, M. Herold, B. Nölchen, G. Judmaier, and C. Huber. 1992. Serum levels of cytokines in chronic liver diseases. Gastroenterology. 103: 264-274.
20 Coker, R. K. and G. J. Laurent. 1998. Pulmonary fibrosis: cytokines in the balance. Eur. Respir. J. 11: 1218-1221.
21 Zhong, X., E. Nishino, and N, Okagami. 2002. Temperature dependence of seedling establishment of a perennial, Dioscorea tokoro. J. Plant. Res. 115: 55-57.
22 Siebenlist, U., G. Franzoso, and K. Brown. 1994. Structure, regulation and function of NF-kappa B. Annu. Rev. Cell. Biol. 10: 405-455.
23 Renard, P. and M. Raes. 1999. The proinflammatory transcription factor NFkappaB: a potential target for novel therapeutical strategies. Cell. Biol. Toxicol. 15: 341-344.
24 Tian, B. and A. R. Brasier. 2003. Identification of a nuclear factor kappa B-dependent gene network. Recent. Prog. Horm. Res. 58: 95-130.
25 Lee, S. C., C. C. Tsai, J. C. Chen, C. C. Lin, M. L. Hu, and S. Lu. 2002. The evaluation of reno- and hepatoprotective effects of huai-shan-yao (Rhizome Dioscoreae). Am. J. Chin. Med. 30: 609-616.
26 Tewtrakul, S. and A. Itharat. 2007. Nitric oxide inhibitory substances from the rhizomes of Dioscorea membranacea. J. Ethnopharmacol. 109: 412-416.