IMMUNE NETWORK

  • 제6권1호
  • /
  • Pages.27-32
  • /
  • 2006
  • /
  • 1598-2629(pISSN)
  • /
  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
권호 표지

오미자 활성성분 DDB의 NF-${\kappa}B$ 신호 전달 및 염증물질 발현 조절

Regulation of Inflammatory Repertoires and NF-${\kappa}B$ Signal Transduction by DDB, an Active Compound from Schizandra Chinensis Baillon

  • 주성수 (중앙대학교 약학대학 면역학교실) ;
  • 유영민 (상지대학교 한의과대학 병리학교실) ;
  • 원태준 (중앙대학교 약학대학 면역학교실) ;
  • 김민정 (중앙대학교 약학대학 면역학교실) ;
  • 이선구 (상지대학교 한의과대학 병리학교실) ;
  • 황광우 (중앙대학교 약학대학 면역학교실) ;
  • 이도익 (중앙대학교 약학대학 면역학교실)
  • Joo, Seong-Soo (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Yoo, Yeong-Min (Department of Oriental Pathology, College of Oriental Medicine, Sangji University) ;
  • Won, Tae-Joon (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Kim, Min-Jung (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Lee, Seon-Goo (Department of Oriental Pathology, College of Oriental Medicine, Sangji University) ;
  • Hwang, Kwang-Woo (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Lee, Do-Ik (Department of Immunology, College of Pharmacy, Chung-Ang University)
  • 발행 : 2006.03.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: Chronic inflammation in the brain has known to be associated with the development of a various neurological diseases including dementia. In general, the characteristic of neuro-inflammation is the activated microglia over the brain where the pathogenesis occurs. Pro-inflammatory repertoires, interleukin-1${\beta}$ (IL-1${\beta}$) and nitric oxide (NO), are the main causes of neuro-degenerative disease, particularly in Alzheimer's disease (AD) which is caused by neuronal destruction. Those pro-inflammatory repertoires may lead the brain to chronic inflammatory status, and thus we hypothesized that chronic inflammation would be inhibited when pro-inflammatory repertoires are to be well controlled by inactivating the signal transduction associated with inflammation. Methods: In the present study, we examined whether biphenyl dimethyl dicarboxylate (DDB), an active compound from Schizandra chinensis Baillon, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS) and IL-1${\beta}$. Western blots were also used for the analysis of NF-${\kappa}B$ and I${\kappa}B$. Results: In the study, we found that DDB effectively inhibited IL-1${\beta}$ as well as NO production in BV-2 microglial cell, and the translocation of NF-${\kappa}B$ was comparably inhibited in the presence of DDB comparing those to the positive control, lipopolysaccharide. Conclusion: The data suggested that the DDB from Schizandra chinensis Baillon may play an effective role in inhibiting the pro-inflammatory repertoires which may cause neurodegeneration and the results imply that the compound suppresses a cue signal of the microglial activation which can induce the brain pathogenesis such as Alzheimer's disease.

키워드

참고문헌

  1. Zhu M, Lin KF, Yeung RY, Li RC: Evaluation of the protective effects of Schizandra chinensis of phase I drug metabolism using a $CCl_4$ intoxication model. J Ethnopharmacol 67; 61-68, 1999 https://doi.org/10.1016/S0378-8741(98)00210-4
  2. Molokovskii DS, Davydov VV, Tiulenev VV: The action of adaptogenic plant preparations in experimental alloxan diabetes. Probl Endokrinol 35;82-87, 1987
  3. Jung GT, Ju IO, Choi JS, Hong JS: The antioxidative, antimicrobial and nitrite scavenging effects of Schizandra chinensis RUPRECHT (Omija) seed. Korean J Food Sci Technol 32;928-935, 2000
  4. Kim OC, Jang HJ: Volatile components of Schizandra chinenesis Bullion. Agric Chem Biotechnol 37;30-36, 1994
  5. Shoji K, Yasufumi O: Effect of gomicin A on liver generation. Planta Med 58;489-482, 1992 https://doi.org/10.1055/s-2006-961532
  6. Shoe HJ, Lee MY, Hwang GS: The effect of Scizandra fructus extract on blood constituents of alloxan-induced diabetes rabbits. J Korean Soc Food Nutr 24;658-662, 1995
  7. Jang EH, Pyo YH, Ahn MS: Antioxidant effect of Omija extracts. Korean J Soc Food Sci 12;372-376, 1996
  8. Kang KW, Kim YG, Kim CW, Kim SG: The anti-fibrogenic effect of a pharmaceutical composition of [5-(2-pyrazinyl)-4-methyl- 1,2-bithiol-3-thione] (oltipraz) and dimethyl-4,4'-dime thoxy-5, 6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB). Arch Pharm Res 25;655-663, 2002 https://doi.org/10.1007/BF02976940
  9. Lowenstein CJ, Dinerman JL, Snyder SH: Nitric oxide: a physiologic messenger. Ann Intern Med 120;227-237, 1994 https://doi.org/10.7326/0003-4819-120-3-199402010-00009
  10. Tsoulfas G, Geller DA: NF-kappaB in transplantation: friend or foe. Transpl Infect Dis 3;212-219, 2001 https://doi.org/10.1034/j.1399-3062.2001.30405.x
  11. Hobbs AJ, Higgs A, Moncada S: Inhibition of nitric oxide synthase as a potential therapeutic target. Annu Rev Pharmacol Toxicol 39;191-220, 1999 https://doi.org/10.1146/annurev.pharmtox.39.1.191
  12. Shin HM, Kim MH, Kim BH, Jung SH, Kim YS, Park HJ, Hong JT, Min KR, Kim Y: Inhibitory action of novel aromatic diamine compound on lipopolysaccharide-induced nuclear translocation of NF-kappaB without affecting IkappaB degradation. FEBS Lett 571;50-54, 2004 https://doi.org/10.1016/j.febslet.2004.06.056
  13. Yamamoto Y, Gaynor RB: IkappaB kinases: key regulators of the NF-kappaB pathway. Trends Biochem Sci 29;72-79, 2004 https://doi.org/10.1016/j.tibs.2003.12.003
  14. Kreutzberg GW: Microglia a sensor for pathological events in the CNS. Trends Neurosci 19;312-318, 1996 https://doi.org/10.1016/0166-2236(96)10049-7
  15. Kim HS, Whang SY, Woo MS, Park JS, Kim WK, Han IO: Sodium butyrate suppresses interferon-gamma, but not lipopolysaccharide- mediated induction of nitric oxide and tumor necrosis factor-alpha in microglia. J Neuroimmunol 151;85-93, 2004 https://doi.org/10.1016/j.jneuroim.2004.02.006
  16. Meda L, Cassatella MA, Szendrei GI, Otvos LJr, Baron P, Villalba M, Ferrari D, Rossi F: Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature 374; 647-650, 1995 https://doi.org/10.1038/374647a0
  17. Selkoe DJ: Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 81;741-766, 2001 https://doi.org/10.1152/physrev.2001.81.2.741
  18. Kim WK, Jang PG, Woo MS, Han IO, Piao HZ, Lee K, Lee H, Joh TH, Kim HS: A new anti-inflammatory agent KL-1037 represses proinflammatory cytokine and inducible nitric oxide synthase (iNOS) gene expression in activated microglia. Neuropharmacology 47;243-252, 2004 https://doi.org/10.1016/j.neuropharm.2004.03.019
  19. Kang KW, Kim YG, Kim CW, Kim SG. The anti-fibrogenic effect of a pharmaceutical composition of [5-(2-pyrazinyl)-4- methyl-1,2-dithiol-3-thione] (oltipraz) and dimethyl-4,4'-demethoxy- 5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB). Arch Pharm Res 25;655-663, 2004 https://doi.org/10.1007/BF02976940
  20. Blasi E, Barluzzi R, Bocchini V, Mazzolla R, Bistoni F: Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus. J Neuroimmunol 27;229-237, 1990 https://doi.org/10.1016/0165-5728(90)90073-V
  21. Bocchini V, Mazzolla R, Barluzzi R, Blasi E, Sick P, Kettenmann H: An immortalized cell line expresses properties of activated microglial cells. J Neurosci Res 31;616-621, 1992 https://doi.org/10.1002/jnr.490310405
  22. Petrova TV, Akama KT, Van Eldik LJ: Selective modulation of BV-2 microglial activation by prostaglandin E (2). Differential effects on endotoxin-stimulated cytokine induction. J Biol Chem 274;28823-288237, 1999 https://doi.org/10.1074/jbc.274.40.28823
  23. Kim WK, Jang PG, Woo MS, Han IO, Piao HZ, Lee K, Lee H, Joh TH, Kim HS: A new anti-inflammatory agent KL-1037 represses proinflammatory cytokine and inducible nitric oxide synthase (iNOS) gene expression in activated microglia. Neuropharmacology 47;243-52, 2004 https://doi.org/10.1016/j.neuropharm.2004.03.019
  24. Min KJ, Pyo HK, Yang MS, Ji KA, Jou I, Joe EH: Gangliosides activate microglia via protein kinase C and NADPH oxidase. Glia 1548;197-206, 2004
  25. Furge LL, Fields PR, Goode WE, Konwinski RR, Tressler MC, Stevens-Truss R: Oltipraz inhibits inducible nitric oxide synthase in vitro and inhibits nitric oxide production in activated microglial cells. Arch. Biochem Biophys 424;163-170, 2004 https://doi.org/10.1016/j.abb.2004.02.018
  26. Joo SS, Won TJ, Lee DI: Potential role of ursodeoxycholic acid in suppression of nuclear factor kappa B in microglial cell line (BV-2). Arch Pharm Res 27;954-960, 2004 https://doi.org/10.1007/BF02975850