Protective Effect of Cordyceps sinensis Extract on Cytokine-induced Cytotoxicity of Pancreatic ${\beta}-cells$

싸이토카인에 의한 췌장 ${\beta}$세포 독성에 대한 동충하초(冬蟲夏草) 추출물의 보호 효과

  • Song, Je-Ho (Division of Beauty Design & Institute for Better Living, Wonkwang University) ;
  • Park, Byung-Hyun (Department of Biochemistry, Medical School and Institute for Medical Sciences, Chonbuk National University) ;
  • Ryu, Do-Gon (Department of Physiology, College of Oriental Medicine, Wonkwang University) ;
  • Kwon, Kang-Beom (Department of Physiology, College of Oriental Medicine, Wonkwang University)
  • 송제호 (원광대학교 생활과학대학 뷰티디자인학부 생활자원개발연구소) ;
  • 박병현 (전북대학교 의학전문대학원 생화학교실 의과학연구소) ;
  • 류도곤 (원광대학교 한의과대학 한방생리학교실) ;
  • 권강범 (원광대학교 한의과대학 한방생리학교실)
  • Published : 2008.08.25

Abstract

In the present study, Cordyceps sinensis extract (CSE) was evaluated to determine if it could protect pancreatic ${\beta}$ cells against cytokine-induced cytotoxicity of RINm5F cells. Treatment of cells with cytokines resulted in a decrease of viability, which was caused by increase of nitric oxide (NO) production. CSE protected cytokine-mediated viability reduction in a concentration-dependent manner. Incubation with CSE also induced a significant suppression of cytokine-induced inducible nitric oxide synthase (iNOS) protein and NO production. The molecular mechanism by which CSE inhibited iNOS protein expression appeared to involve the inhibition of $NF-{\kappa}B$ activation. The cytokine-stimulated RIN cells showed increases in $NF-{\kappa}B$ binding activity compared to unstimulated cells. However, pretreatment with CSE inhibited cytokines-induced $NF-{\kappa}B$ activation in RINm5F cells.

Keywords

References

  1. 辛民敎. 원색 임상본초학. 영림사, p 270, 1986
  2. 錢伯文. 抗癌中藥的臨床效果. 上海飜譯出版公司, pp 106-107, 1987
  3. Foulis, A.K., Liddle, C.N., Farquharson, M.A., Richmond, J.A., Weir, R.S. The histopathology of the pancreas in type 1 (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom. Diabetologia 29: 267-274, 1986 https://doi.org/10.1007/BF00452061
  4. Eizirik, D.L., Flodstrom, M., Karlsen, A.E., Welsh, N. The harmony of the spheres: inducible nitric oxide synthase and related genes in pancreatic ${\beta}$ cells. Diabetologia 39: 875-890, 1996
  5. Mandrup-Poulsen, T. The role of interleukin-$1{\beta}$ in the pathogenesis of IDDM. Diabetologia 39: 1005-1029, 1996 https://doi.org/10.1007/BF00400649
  6. Southern, C., Schulster, D., Green, I.C. Inhibition of insulin secretion by interleukin-$1{\beta}$ and tumour necrosis factor-${\alpha}$ via an L-arginine-dependent nitric oxide generating mechanism. FEBS Letters 276: 42-44, 1990 https://doi.org/10.1016/0014-5793(90)80502-A
  7. Eizirik, D.L., Sandler, S., Welsh, N., Cetkovic-Cvrlje, M., Nieman, A., Geller, D.A., Pipeleers, D.G., Bendtzen, K., Hellerstrom, C. Cytokines suppress human islet function irrespective of their effects on nitric oxide generation. Journal of Clinical Investigation 93: 1968-1974, 1994 https://doi.org/10.1172/JCI117188
  8. Kwon, K.B., Kim, J.H., Lee, Y.R., Lee, H.Y., Jeong, Y.J., Rho, H.W., Ryu, D.G., Park, J.W., Park, B.H. Amomum xanthoides extract prevents cytokine-induced cell death of RINm5F cells through the inhibition of nitric oxide formation. Life Sci 73: 181-191, 2003 https://doi.org/10.1016/S0024-3205(03)00267-4
  9. Kim, E.K., Kwon, K.B., Han, M.J., Song, M.Y., Lee, J.H., Lv, N., Ka, S.O., Yeom, S.R., Kwon, Y.D., Ryu, D.G., Kim, K.S., Park, J.W., Park, R., Park, B.H. Coptidis rhizoma extract protects against cytokine-induced death of pancreatic $\beta$-cells through suppression of NF-${\kappa}B$ activation. Experimental and Molecular Medicine, 39(2):149-159, 2007 https://doi.org/10.1038/emm.2007.17
  10. Kim, E.K., Kwon, K.B., Han, M.J., Song, M.Y., Lee, J.H., Lv, N., Choi, K.B., Ryu, D.G., Kim, K.S., Park, J.W., Park, B.H. Inhibitory effect of Artemisia capillaris extract on cytokine-induced nitric oxide formation and cytotoxicity of RINm5F cells. International Journal of Molecular Medicine. 19: 535-540, 2007
  11. 박성호, 서운교, 정지천. 冬蟲夏草의 抗突然變異 活性에 관한 硏究. 대한한방내과학회지 21(2):309-318, 2000
  12. 민건우, 박종혁, 윤철호, 정지천, 신억섭, 한영환. 冬蟲夏草가 Hydrocortisone을 투여한 흰쥐의 Nitric Oxide Synthase 활성 및 Testosterone 함량에 미치는 영향. 대한한방내과학회지 21(3):389-398, 2000
  13. 정희선, 이종록, 김상찬. 冬蟲夏草추출물이 Ovalbumin으로 유도된 喘息의 Cytokine에 미치는 영향. 동의생리병리학회지 20(4):973-979, 2006
  14. Xie, Q.W., Cho, H.J., Calaycay, J., Mumford, R.A., Swiderek, K.M., Lee, T.D., Ding, A., Troso, T., Nathan, C. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256: 225-228, 1992 https://doi.org/10.1126/science.1373522
  15. Jeong, J.Y., Jue, D.M. Chloroquine inhibits processing of tumor necrosis factor in lipopolysaccharide-stimulated RAW 264.7 macrophages. Journal of Immunology 158: 4901-4907, 1997
  16. Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analysis Biochemistry 72: 248-254, 1976 https://doi.org/10.1016/0003-2697(76)90527-3
  17. Cetkovic-Cvrlje, M., Eizirik, D.L. TNF-${\alpha}$ and IFN-${\gamma}$ potentiate the deleterious effects of IL-$1{\beta}$ on mouse pancreatic islets mainly via generation of nitric oxide. Cytokine 6: 399-406, 1994 https://doi.org/10.1016/1043-4666(94)90064-7
  18. Heitmeier, M.R., Scarim, A.L., Corbett, J.A. Interferon-$\gamma$ increases the sensitivity of islets of Langerhans for inducible nitric-oxide synthase expression induced by interleukin 1. Journal of Biological Chemistry 272: 13697-13704, 1997 https://doi.org/10.1074/jbc.272.21.13697
  19. Lortz, S., Tiedge, M., Nachtwey, T., Karlsen, A.E., Nerup, J., Lenzen, S. Protection of insulin-producing RINm5F cells against cytokine-mediated toxicity through overexpression of antioxidant enzymes. Diabetes 49: 1123-1130, 2000 https://doi.org/10.2337/diabetes.49.7.1123
  20. Kwon, K.B., Kim, E.K., Lim, J.G., Shin, B.C., Han, S.C., Song, B.K., Kim, K.S., Seo, E.A., Ryu, D.G. Protective effect of Coptidis Rhizoma on S-nitroso-N-acetylpenicillamine (SNAP)-induced apoptosis and necrosis in pancreatic RINm5F cells. Life Sciences 76: 917-929, 2005 https://doi.org/10.1016/j.lfs.2004.10.008
  21. Baeuerle, P.A., Henkel, T. Function and activation of NF-${\kappa}B$ in the immune system. Annual Review of Immunology 12: 141-179, 1994 https://doi.org/10.1146/annurev.iy.12.040194.001041
  22. Baldwin, A.S. Jr. The NF-${\kappa}B$ and I${\kappa}B$ proteins: new discoveries and insights. Annual Review of Immunology 14: 649-683, 1996 https://doi.org/10.1146/annurev.immunol.14.1.649
  23. Sorli, C.H., Zhang, H.J., Armstrong, M.B., Rajotte, R.V., Maclouf, J., Robertson, R.P. Basal expression of cyclooxygenase-2 and nuclear factor-interleukin 6 are dominant and coordinately regulated by interleukin 1 in the pancreatic islet. Proc Natl Acad Sci USA 95: 1788-1793, 1998