Coptis chinensis Extract Inhibits the Production of Inflammatory Mediators and Delayed Type Hypersensitivity in Mice

  • Lee, Yeon-Ah (Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyung Hee University) ;
  • Hong, Seung-Jae (Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyung Hee University) ;
  • Lee, Sang-Hoon (Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyung Hee University) ;
  • Kim, Kyoung-Soo (East-West Bone & Joint Research Center, Kyung Hee University East-West Neo Medical Center) ;
  • Park, Eun-Kyung (East-West Bone & Joint Research Center, Kyung Hee University East-West Neo Medical Center) ;
  • Jung, Ki-Won (Life Science Research Center, SK Chemicals) ;
  • Han, Chung-Soo (Department of Orthopedic Surgery, College of Medicine, Kyung Hee University) ;
  • Yoo, Myung-Chul (Department of Orthopedic Surgery, College of Medicine, Kyung Hee University) ;
  • Yang, Hyung-In (Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyung Hee University)
  • 발행 : 2008.03.30

초록

Background: Coptis chinensis rhizome has been used as a medicinal herb in traditional Oriental medicine. We investigated the effects of Coptis chinensis extract on inflammatory mediators and delayed type hypersensitivity in mice. Methods: The inhibitory effect of ethanolic extract of Coptis chinensis (CCE) on cell proliferation was evaluated using MTS assay. The lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the Con A-activated mouse splenocytes were cultured with various concentrations of CCE. Total nitric oxide (NO) production was determined by Griess reaction. The amounts of secreted prostaglandine E2 ($PGE_2$), interleukin (IL)-2 and IFN-${\gamma}$ were measured by ELISA. To investigate the in vivo anti-inflammatory effect of CCE, oxazolone-induced delayed type hypersensitivity (DTH) model was used. Results: The CCE at $100{\mu}g/ml$ significantly blocked the LPS-induced production of pro-inflammatory mediators (NO and PGE) in RAW264.7 macrophages. Also, it significantly inhibited cell proliferation and cytokine (IL-2 and IFN-${\gamma}$) production in splenocytes. Furthermore, when splenocytes from CCE fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and cytokine production were significantly inhibited. In addition, CCE decreased in vivo inflammation in oxazolone-induced DTH model mice. Conclusion: We suggest that Coptis chinensis can be used as an anti-inflammatory drug by exerting an inhibitory effect in inflammatory mediator- and cell-mediated inflammation.

키워드

참고문헌

  1. Wu MJ, Wang L, Ding HY, Weng CY, Yen JH. Glossogyne tenuifolia acts to inhibit inflammatory mediator production in a macrophage cell line by downregulating LPS-induced NF-Kb. J Biomed Sci 11:186-199, 2004
  2. Dinarello CA. Interleukin-1, interleukin-1 receptors and interlekin-1 receptor antagonist. Int Rev Immunol 16:457-499, 1998 https://doi.org/10.3109/08830189809043005
  3. Nathan C. Natural resistance and nitric oxide. Cell 82:873-876, 1995 https://doi.org/10.1016/0092-8674(95)90019-5
  4. Fenton MJ, Golenbock DT. LPS-binding proteins and receptors. J Leukoc Biol 64:25-32, 1998 https://doi.org/10.1002/jlb.64.1.25
  5. Glauser MP. The inflammatory cytokines. New developments in the pathophysiology and treatment of septic shock. Drugs 52(suppl):9-17, 1996
  6. Duan H, Zhang Y, Xu J, Qiao J, Suo Z, Hu G, Mu X. Effect of anemonin on NO, ET-1 and ICAM-1 production in rat intestinal microvascular endothelial cells. Journal of Ethnopharmacology 104:362-366, 2006 https://doi.org/10.1016/j.jep.2005.09.034
  7. Lefkowith JB. Cyclooxygenase-2 specificity and its clinical implications. American Journal of Medicine 106:43S-50S, 1999 https://doi.org/10.1016/S0002-9343(99)00003-0
  8. Solomon SD. Cyclooxygenase-2 inhibitors and cardiovascular risk. Curr Opin Cardiol 21:613-617, 2006
  9. Ikram M. A review on the chemical and pharmacological aspects of genus Berberis. Planta Med 28:353-358, 1975 https://doi.org/10.1055/s-0028-1097869
  10. Schmeller T, Latz-Bruning B, Wink M. Biochemical activities of berberine, palmaltine and sanguinarine mediating chemical defense against microorganisms and herbivores. Phytochemistry 44:257-266, 1997 https://doi.org/10.1016/S0031-9422(96)00545-6
  11. Kettmann V, Kosfalova D, Jantova S, Cernakova M, Drimal J. In vitro cytotoxicity of berberine against HeLa and L1210 cancer cell lines. Pharmazie 59:548-551, 2004
  12. Kuo CL, Chi CW, Liu TY. The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett 20:127-137, 2004
  13. Pathak N, Khandelwal S. Oxidative stress and apoptotic changes in murine splenocytes exposed to cadmium. Toxicology 220:26-36, 2006 https://doi.org/10.1016/j.tox.2005.11.027
  14. Blaylock BL, Newsom KK, Holladay SD, Shipp BK, Bartow TA, Mehendale HM. Topical exposure to chlordane reduces the contact hypersensitivity response to oxazolone in BALB/c mice. Toxicology Letters 81:205-211, 1995 https://doi.org/10.1016/0378-4274(95)03436-6
  15. Mayer B, Hemmens B. Biosynthesis and action of nitric oxide in mammalian cells. Trends Biochem Sci 22:477-481, 1997 https://doi.org/10.1016/S0968-0004(97)01147-X
  16. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J 6:3051-3064, 1992 https://doi.org/10.1096/fasebj.6.12.1381691
  17. Akarasereenont P, Bakhle YS, Thiemermann C, Vane JR. Cytokine-mediated induction of cyclo-oxygenase 2 by activation of tyrosine kinase in bovine endothelial cells stimulated by bacterial lipopolysaccharide. Br J Pharmacol 115:401-408, 1994
  18. Rothenberg EV, Diamond RA, Pepper KA, Yang JA. IL-2 gene inducibility in T cells before T cell receptor expression. Changes in signaling pathways and gene expression requirements during intrathymic maturation. The Journal of Immunology 144:1614-1624, 1990
  19. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100:655-669, 2000 https://doi.org/10.1016/S0092-8674(00)80702-3
  20. Mullen AC, High FA, Hutchins AS. Role of T-bet in commitment of Th1 cells before IL-12-depedent selection. Science 292:1907-1910, 2001 https://doi.org/10.1126/science.1059835
  21. Schwartz RH. Natural regulatory T cells and self-tolerance. Nature Immunology 6:327-330, 2005 https://doi.org/10.1038/ni1184
  22. Verdrngh M, Jonsson IM, Holmdahl R, Tarkowski A. Genistein as an anti-inflammatory agent. Inflammation Research 52:341-346, 2003 https://doi.org/10.1007/s00011-003-1182-8
  23. Yasukawa K, Takido M, Ikekawa T, Shimada F, Takeuchi M, Nakagawa S. Relative inhibitory activity of berberine- type alkaloids against 12-O-tetra decanoylphorbol-13-acetate-induced inflammation in mice. Chem Pharm Bull 39:1462-1465, 1991 https://doi.org/10.1248/cpb.39.1462
  24. Fukuda K, Hibiya Y, Mutoh M, Koshiji M, Akao S, Fujiwara H. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol 66:227-233, 1999 https://doi.org/10.1016/S0378-8741(98)00162-7
  25. Lee DU, Kang YJ, Park MK, Lee YS, Seo HG, Kim TS, Kim CH, Chang KC. Effects of 13-alkylsubstituted berberine alkaloids on the expression of COX-II, TNF-a, iNOS, and IL-12 production in LPS stimulated macrophages. Life Sci 73:1401-1412, 2003 https://doi.org/10.1016/S0024-3205(03)00435-1
  26. Li B, Shang JC, Zhou QX. Study of total alkaloids from Rhizoma Coptis Chinensis on experimental gastric ulcers. Chin J Integr Med 11:217-221, 2005 https://doi.org/10.1007/BF02836508
  27. Liang KW, Ting CT, Yin SC, Chen YT, Lin SJ, Liao JK, Hsu SL. Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury. Biochem Pharmacol 71:806-817, 2006