Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
권호 표지

Wild Ginseng Exerts Anti-inflammatory Effects via $NF-{\kappa}B$ inactivation in RAW 264.7 Cells

장뇌산삼의 $NF-{\kappa}B$ 억제를 통한 RAW 264.7 세포에서의 항염증 효과

  • Ahn, Sang-Hyun (Department of Anatomy, Department of Physiology, Oriental Medicine College) ;
  • Kim, Jin-Tack (Department of Anatomy, Department of Physiology, Oriental Medicine College) ;
  • Shin, Heung-Mook (Department of Physiology, Oriental Medicine College, Oriental Medical Bio-Renovatio Institute, Dongguk University)
  • 안상현 (동국대학교 한의과대학 해부학교실, 생리학교실) ;
  • 김진택 (동국대학교 한의과대학 해부학교실, 생리학교실) ;
  • 신흥묵 (생리학교실, 동국대학교 한의바이오혁신사업단)
  • Published : 2007.04.25
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Abstract

Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are important inflammatory mediators that have been implicated in pathogenesis of inflammation and certain types of human cancers. The present study was designed in order to determine whether Wild ginseng (Panax ginseng C. A. Mayer) could modulate $I{\kappa}B$-kinase (IKK), iNOS and COX-2 gene expression and its immune responses in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS, 1 ${\mu}/m{\ell}$). Wild ginseng extract dose-dependantly (*0.5 - 2 ${\mu}/m{\ell}$) decreased the LPS-induced IKK, iNOS and COX-2 mRNA expression and its immune responses. Moreover, it inhibited unclear factor (NF)-${\kappa}B$ immune response by LPS. These data be likely to indicate that Wild ginseng may acts as inflammatory regulator and may be possible to develope a useful agent for inflammatory diseases.

Keywords

References

  1. 徐樹柟, 朱兵占. 神農本草經. 河北, 河北科學技術出版社. p 10, 1996
  2. Lee, H.C., Hwang, S.G., Lee, Y.G., Sohn, H.O., Lee, D.W., Hwang, S.Y., Kwak, Y.S., Wee, J.J., Joo, W.H., Cho, Y.K., Moon, J.Y. In vivo effects of Panax ginseng extracts on the cytochrome P450-dependent monooxygenase system in the liver of 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed guinea pig. Life Sci. 71(7):759-769, 2002 https://doi.org/10.1016/S0024-3205(02)01742-3
  3. 성금수, 전철, 권용훈, 김경현, 장재철. 홍삼추출물 투여가 생쥐 간에서 항산화 효소 활성과 지질과산화에 미치는 효과. J Ginseng Res. 24(1):29-34, 2000
  4. 김정선, 김규원, 최강주, 곽영규, 임광식, 이경희, 정해영. 홍삼 사포닌의 항산화활성 성분 Screening. Korean J Ginseng sci. 20(2):173-178, 1996
  5. Park, Y.C., Lee, C.H., Kang, H.S., Kim, K.W., Chung, H.T., Kim, H.D. Ginsenoside-Rh1 and Rh2 inhibit the induction of nitric oxide synthesis murine peritoneal macrophage. Biochem. Mol. Biol. Int. 40: 751-757, 1996
  6. Oh, G.S., Pae, H.O., Choi, B.M., Seo, E.A., Kim, D.H., Shin, M.K., Kim, J.D., Kim, J.B., Chung, H.T. 20(S)-protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear $factor-{\kappa}B$ in RAW264.7 macrophages stimulated with lipopolysaccharide. Cancer Letters. 205: 23-29, 2004 https://doi.org/10.1016/j.canlet.2003.09.037
  7. Jung, C.H., Seog, H.M., Choi, I.W., Choi, H.D., Cho, H.Y. Antioxidant activities of cultivated and wild korean ginseng leaves. Food Chemistry. 92: 535-540, 2005a https://doi.org/10.1016/j.foodchem.2004.08.021
  8. Jung, C.H., Seog, H.M., Choi, I.W., Choi, H.D., Cho, H.Y. Effects of wild ginseng (Panax ginseng C.A. Meyer) leaves on lipid peroxidation levels and antioxidant enzyme activities in streptozotocin diabetic rats. J Ethnopharmacol. 98(3):245-250, 2005b https://doi.org/10.1016/j.jep.2004.12.030
  9. 안상현, 조성준, 윤창환, 조민경, 김진택, 신흥묵. 장뇌산삼이 Benzopyrene으로 유도된 간조직의 $TNF-{\alpha}$와 COX-2의 면역조직학적 분포에 미치는 영향. 동의생리병리학회지 19(6): 1568-1572, 2005
  10. 곡경승, 이선구, 권기록. pH 및 전해질 조절 산양산삼 증류약침의 apoptosis에 관한 실험적 연구. 대한침구학회지 21(6):1-17, 2004
  11. Lee, H.J. Studies on the comparison of bioactive compounds and cell cultures of panax ginseng C.A. Meyer and moumtain ginseng. MS Thesis, Ajou University, Korea. 2000
  12. Yoo, B.S., Lee, H.J., Byun, S.Y. Differences in phenolic compoundsd between korean ginseng and moumtain ginseng. Korean J. Biotechnology and Bioengineering. 15: 120-124, 2000
  13. Lee, H.J, Yoo, B.S., Byun, S.Y. Differences in free amino acids between korean ginseng and mountain ginseng. Korean J. Biotechnology and Bioengineering. 15: 133-328, 2000
  14. Lowenstein, C.J, Alley, E.W, Raval, P., Snowman, A.M, Snyder S.H, Russell S.W, Murphy W.J. Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc Natl Acad Sci USA. 11. Stuehr DJ, Marletta MA. Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc Natl Acad Sci USA. 82(22):7738-7742, 1985
  15. Belvisi, M., Barnes, P.J., Larkin, S., Yacoub, M., Tadjkarimi, S., Williams, T.J., Mitchell, J.A. Nitric oxide synthase activity is elevated in inflammatory lung disease in humans. Eur J Pharmacol. 283(1-3):255-258, 1995 https://doi.org/10.1016/0014-2999(95)00421-G
  16. RothkOtter, H.J., Pabst, R., Bailey, M. Lymphocyte migration in the intestinal mucosa : entry, transit and emigration of lymphoid cells and the influence of antigen. Vetrinary Immuno immunopath. 72: 157-165, 1999 https://doi.org/10.1016/S0165-2427(99)00128-2
  17. Tsujii, M., Kawano, S., Tsuji, S., Sawaoka, H., Hori, M., DuBois, R.N. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93(5):705-716, 1998 https://doi.org/10.1016/S0092-8674(00)81433-6
  18. Je, J.H., Lee, J.Y., Jung, K.J., Sung, B., Go, E.K., Yu, B.P., Chung, H.Y. NF-kappaB activation mechanism of 4-hydroxyhexenal via NIK/IKK and p38 MAPK pathway. FEBS Lett. 566(1-3):183-189, 2004 https://doi.org/10.1016/j.febslet.2004.04.037
  19. Chandrasekar, B., Marelli-Berg, F.M., Tone, M., Bysani, S., Prabhu, S.D., Murray, D.R. Beta-adrenergic stimulation induces interleukin-18 expression via beta2-AR, PI3K, Akt, IKK, and NF-kappaB. Biochem Biophys Res Commun. 319(2):304-311, 2004 https://doi.org/10.1016/j.bbrc.2004.04.185
  20. Bozinovski, S., Jones, J.E., Vlahos, R., Hamilton, J.A., Anderson, G.P. Granulocyte/대식세포-colony-stimulating factor (GM-CSF) regulates lung innate immunity to lipopolysaccharide through Akt/Erk activation of NFkappa B and AP-1 in vivo. J Biol Chem. 277(45):42808-42814, 2002 https://doi.org/10.1074/jbc.M207840200
  21. Agarwal, A., Das, K., Lerner, N., Sathe, S., Cicek, M., Casey, G., Sizemore, N. The AKT/I kappa B kinase pathway promotes angiogenic/metastatic gene expression in colorectal cancer by activating nuclear factor-kappa B and beta-catenin. Oncogene. 24(6):1021-1031, 2005 https://doi.org/10.1038/sj.onc.1208296
  22. Lowenstein, C.J., Alley, E.W., Raval, P., Snowman, A.M., Snyder, S.H., Russell, S.W., Murphy, W.J. Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc Natl Acad Sci USA. 90(20):9730-9734, 1993
  23. Xie, Q.W, Kashiwabara, Y., Nathan, C. Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J Biol Chem. 269(7):4705-4708, 1994
  24. Baeuerle, P.A. $I{\kappa}B-NF-{\kappa}B$ structure: at the interface of inflammation control. Cell. 95: 729-731, 1998 https://doi.org/10.1016/S0092-8674(00)81694-3
  25. Hu, Y., Baud, V., Delhase, M., Zhang, P., Deerinck, T., Ellisman, M., Johnson, R. Karin Abnomal morphogenesis but intact IKK activation in mice lacking the $IKK{\alpha}$ subunit of IkB kinase. Science. 284: 316-320, 1999 https://doi.org/10.1126/science.284.5412.316
  26. Takeda, K., Takeuchi, O,, Tsujimura, T., Itami, S., Adachi, O., Kawai, T., Sanjo, H., Yoshikawa, K., Terada, N., Akira, S. Limb and skin abnomalities in mice lacking IKK ${\alpha}$. Science. 284: 313-316, 1999 https://doi.org/10.1126/science.284.5412.313
  27. LiQ, Van Antwerp D., Mercurio F., Lee K.F., Verma IM. Severe liver degeneration in mice lacking the $I{\kappa}B$ kinase 2 gene. Science. 284; 321-325, 1999 https://doi.org/10.1126/science.284.5412.321
  28. Pan, M.H, Yn, S., Lin-shiau, Lin, J.K. Comparative Studies on the suppression of nitric oxide synthase by curcumin and Its Hydrogenated metabolites through down-regulation of $I{\kappa}B$ kinase and $NF-{\kappa}B$ activation in macrophages. Biochem. Pharmacol. 60: 1665-1676, 2000 https://doi.org/10.1016/S0006-2952(00)00489-5
  29. Lo, A.H., Liang, Y.C, Shoei-Yn Lin-Shiau, Ho, C.T., Lin, J.K. Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating $NF-{\kappa}B$ in mouse macrophages. Carcinogenesis. 23(6):983-991, 2002 https://doi.org/10.1093/carcin/23.6.983
  30. Seo, W.G., Pae, H.O., Oh, G.S., Chai, K.Y., Yun, Y.G., Kwon, T.O., Chung, H.T. Inhibitory effect of ethyl acetate fraction from Cudrania tricuspidata on the expression of nitric oxide synthase gene in RAW 264.7 macrophages stimulated with interferon-and lipopolysaccharide. Gen Pharmacol. 35: 21-28, 2000 https://doi.org/10.1016/S0306-3623(01)00086-6
  31. Seo, W.G., Pae, H.O., Oh, G.S., Chai, K.Y., Kwon ,T.O., Yun, Y.G., Kim, N.Y., Chung, H.T. Inhibitory effects of methanol extracts of Cyrerus rotundus rhizomes on nitric oxide and superoxide production by murine macrophages cell line, RAW 264.7 cells. J Ethnopharmacol. 76: 59-64, 2001 https://doi.org/10.1016/S0378-8741(01)00221-5
  32. Lee, B.G., Kim, S.H., Zee, O.P., Lee, K.R., Lee, H.Y., Han, J.W., Lee, H.W. Suppression of inducible nitric oxide synthase expression in RAW 264.7 macrophages by two-carboline alkaloids extractes from Melia azedarach. Eur. J. Pharmacol. 406: 301-309, 2000 https://doi.org/10.1016/S0014-2999(00)00680-4
  33. 이동언, 이재령, 김영우, 권영규, 변성희, 신상우, 서성일, 권택규, 변준석, 김상찬. 금은화 및 금은화전초가 RAW 264.7 cell에서 LPS로 유도된 NO의 생성, iNOS, COX-2 및 cytokine에 미치는 영향. 동의생리병리학회지 19(2):481-489, 2005
  34. 변성희, 양재하, 김상찬. 현삼메탄올 추출물이 LPS로 유도된 Raw 264.7 cell에서의 $TNF-{\alpha},\;IL-1{\beta},$ IL-6 및 nitric oxide 생성에 미치는 영향. 대한본초학회지 20(2):7-16, 2005
  35. Tan, C.M., Xenoyannis, S., Feldman, R.D. Oxidant stress enhances adenyl cyclaseactivation. Circ Res. 77(4):710-717, 1995 https://doi.org/10.1161/01.RES.77.4.710