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NO와 Pro-Inflammatory Cytokine의 억제를 통한 호라복(胡蘿蔔)의 항염증효과

Roots of Daucus carota sativa abrogates acute phase of Inflammation by the Inhibition of NO and Pro-Inflammatory Cytokine Production

  • 이동진 (대구한의대학교 안이비인후피부과학교실) ;
  • 박상미 (대구한의대학교 방제학교실) ;
  • 황보민 (대구한의대학교 안이비인후피부과학교실) ;
  • 정태영 (대구한의대학교 진단학교실) ;
  • 김상찬 (대구한의대학교 방제학교실) ;
  • 지선영 (대구한의대학교 안이비인후피부과학교실)
  • Lee, Dong-Jin (Department of opthalmology and otolaryngology and dermatology, College of Korean Medicine, Daegu Haany University) ;
  • Park, Sang-Mi (College of Korean Medicine, Daegu Haany University) ;
  • Hwangbo, Min (Department of opthalmology and otolaryngology and dermatology, College of Korean Medicine, Daegu Haany University) ;
  • Jung, Tae-Young (College of Korean Medicine, Daegu Haany University) ;
  • Kim, Sang-Chan (College of Korean Medicine, Daegu Haany University) ;
  • Jee, Seon-Young (Department of opthalmology and otolaryngology and dermatology, College of Korean Medicine, Daegu Haany University)
  • 투고 : 2013.04.11
  • 심사 : 2013.05.10
  • 발행 : 2013.05.25

초록

Objectives : Daucus carota sativa has been frequently used as food supplements in many of the Asian countries, and a nutritional medical drug in traditional medicine. This research investigated the effects of Daucus carota sativa extract (DCE) on acute phases of inflammation in Raw 264.7 cells treated with lipopolysaccharide (LPS) in terms of the inhibition of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines production. Methods : NO, $PGE_2$, tumor necrosis factor (TNF)-${\alpha}$, interleukin-$1{\beta}$ and interleukin-6 contents were assayed by ELISA, and expressions of inflammation-related proteins such as inducible NO synthase (iNOS) were determined by immunoblot analyses. Results : DCE treatment attenuated the LPS ability to increase the productions of NO and $PGE_2$ as well as the protein level of iNOS in a concentration-dependent manner. Consistently, treatment of the cells with DCE suppressed the production of TNF-${\alpha}$, interleukin-$1{\beta}$ and interleukin-6. DCE also caused decreases of inhibitor of ${\kappa}B{\alpha}$ phosphorylation induced by LPS in the cells, which means DCE inhibition of NF-${\kappa}B$ activity. Furthermore, DCE blocked LPS-induced phosphorylation of p38 and SAPK/JNK. Conclusion : This study showing here may be of help to understand the action mechanism of DCE, and provide the information for the medical use of Daucus carota sativa for the inflammatory disease.

키워드

참고문헌

  1. Kim CM, Shin MG, Ahn DG, Lee GS, Kang BS, Kang SS. The Chinese Herbal Dictionary. Seoul:Jeongdam. 1997;6124-6.
  2. Kim TJ. Wild Flowers and Resources Plants in Korea (3). Seoul:SNU Press. 2008;451.
  3. Roh SR, Kim DH. Anti-tumor Effect of Carrot(Docus carota L.) Extracts in the Human Lung Cancer Cell Line NCI-H1299. J East Asian Soc Dietary Life. 2002;12:289-98.
  4. Han EJ, Roh SB, Bae SJ. Cytotoxicity of Daucus Carota L. on Various Cancer Cells. J Korean Soc Food Sci Nutr. 2000;29:153-60.
  5. Jeon EJ, Kim JS, Park YK, Kim TS, Kang MH. Protective Effect of Yellow-Green Vegetable Juices on DNA Damage in Chinese Hamster Lung Cell Using Comet Assay. The Korean Nutrition Society. 2003;36:24-31.
  6. Kim M, Kim M, Shin D, Song C, Lee H. Growth-inhibiting effects of vegetable extracts on Beneficial and Harmful Human Intestinal Bacteria. Agric Chem Biotechnol. 2001;44: 65-70.
  7. Gilani AH, Shaheen F, Saeed SA. Cardiovascular Actions of Daucus carota. Arch Pharm Res. 1994;17:150-3. https://doi.org/10.1007/BF02974250
  8. Ha JL, Bae JS, Park MK, Kim YU, Ha SH, Bae JM, et al. Quantitative Analysis of Carotenoids in Carrot Cultivars Produced in Korea. Journal of the Environmental Sciences. 2009;18:1135-41. https://doi.org/10.5322/JES.2009.18.10.1135
  9. Lee YS, Kim HS, Kim SK, Kim SD. IL-6 mRNA Expression in Mouse Peritoneal Macrophages and NIH3T3 Fibroblasts in Response to Candida albicans. J Microbiol Biotechnol. 2000;10:8-15.
  10. Higuchi M, Higashi N, Taki H, Osawa T. Cytolytic mechanism of activated macrophages. Tumor necrosis factor and L-arginine-dependent mechanism acts as synergistically as the major cytolytic mechanism of activated macrophages. J Immunol. 1990;144:1425-31.
  11. McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JA. Cytokines and nitric oxides in islet inflammation and diabetes. Proc Soc Exp Biol Med. 1996;211:24-32. https://doi.org/10.3181/00379727-211-43950D
  12. Corbett JA, Mac Daniel ML. Intraislet release of interleukin-1 inhibits beta cell function by inducing beta cell expression of inducible nitric oxide syntheses. J Exp Med. 1995; 181:559-68. https://doi.org/10.1084/jem.181.2.559
  13. Cetkovic-Cvrlje M, Eizirik DL. TNF and $IFN{\gamma}$ potentiate the deleterious effects of IL-$1{\beta}$ on mouse pancreatic islets mainly via generation of nitric oxide. Cytokine. 1994; 6:399-406. https://doi.org/10.1016/1043-4666(94)90064-7
  14. Kook YB. Effect of Hwangryunhaedok-tang on Blood Pressure and Renal Functions in Spontaneously Hypertensive Rats. J of Herbal Prescription. 2002;10:113-29.
  15. Aeberli D, Oertle S, Mauron H, Reichenbach S, Jordi B, Villiger PM. Inhibition of the TNF-pathway: use of infliximab and etanercept as remission-inducing agents in cases of therapy-resistant chronic inflammatory disorders. Swiss Med Wkly. 2002;132:414-22.
  16. Delgado AV, McManus AT, Chambers JP. Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance. P Neuropeptides. 2003;37:355-61. https://doi.org/10.1016/j.npep.2003.09.005
  17. The Korean Society of Pathologists. Pathology. Seoul:KMS. 2007;76-108.
  18. Chen F, Castranova V, Shi X. New insights into the role of nuclear factor-kappaB in cell growth regulation. Am J Pathol. 2001; 159:387-97. https://doi.org/10.1016/S0002-9440(10)61708-7
  19. Jirik FR, Podor TJ, Hirano T, Kishimoto T, Loskutoff DJ, Carson DA, et al. Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol. 1989;142:144-7.
  20. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992;6:3051-64.
  21. Grosch S, Maier TJ, Schiffmann S, Geisslinger G. Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst. 2006;98:736-47. https://doi.org/10.1093/jnci/djj206
  22. Sohn GH, Kim SH. Antitumor Activity of Bupleuri Radix and Artemisiae capillaris Herba and Synergistic Effect with Anticancer Drugs. KOMS. 1995;16:414-32.
  23. Dong C, Davis RJ, Flavell RA. MAP kinases in the immune response. Annu Rev Immunol. 2002;20:55-72. https://doi.org/10.1146/annurev.immunol.20.091301.131133
  24. Mori M. Regulation of nitric oxide synthesis and apoptosis by arginase and arginine recycling. J Nutr. 2007;137:1616S-20S.
  25. Posadas I, Terencio MC, Guillen I, Ferrandiz ML, Coloma J, Paya M, et al. Co-regulation between cyclo-oxygenase-2 and inducible nitric oxide synthase expression in the time-course of murine inflammation. Naunyn Schmiedebergs Arch Pharmacol. 2000;361: 98-106. https://doi.org/10.1007/s002109900150
  26. Yun HY, Dawson VL, Dawson TM. Neurobiology of nitric oxide. Crit Rev Neurobiol. 1996;10:291-316. https://doi.org/10.1615/CritRevNeurobiol.v10.i3-4.20
  27. Weisz A, Cicatiello I, Esumi H. Regulation of the mouse inducible-type nitric oxide synthase gene promoter by interferon-gamma, bacterical lipopolysaccharide and NG- monomethyl- L-arginene. Biochem J. 1996;316:209-15. https://doi.org/10.1042/bj3160209
  28. McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie QW, Nathan CF, et al. Suppression of arthritis by an inhibitor of nitic oxide synthase. J Exp Med. 1993; 178:749-54. https://doi.org/10.1084/jem.178.2.749
  29. Seo WG, Pae HO, Oh GS, Chai KY, Yun YG, Kwon TO, et al. Inhibitory effects 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. 2000;35:21-8. https://doi.org/10.1016/S0306-3623(01)00086-6
  30. Chiou WF, Chou CJ, Chen CF. Camptothecinsuppresses nitric oxide biosynthesis in RAW264.7 macrophages. Life Sci. 2001;69:625-35. https://doi.org/10.1016/S0024-3205(01)01154-7
  31. Lee BG, Kim SH, Zee OP, Lee KR, Lee HY, Han JW, et al. Suppression of inducible nitric oxide synthase expression in RAW 264.7 macrophages by two-carboline alkaloids extracted from Melia azedarach. Eur J Pharmacol. 2000;406:301-9. https://doi.org/10.1016/S0014-2999(00)00680-4
  32. Seo WG, Pae HO, Oh GS, Kim NY, Kwon TO, Shin MK, et al. The aqueous extract of Rhodiola sachalinensis root enhances the expression of inducible nitric oxide synthase gene in RAW 264.7 macrophages. J Ethnopharmacol. 2001;76:119-23. https://doi.org/10.1016/S0378-8741(01)00220-3
  33. Kawamata H, Ochiai H, Mantani N, Terasawa K. Enhanced expression of inducible nitric oxide synthase by Juzen-taiho-to in LPS-activated RAW 264.7 cells, a murine macrophage cell line. Am J Chin Med. 2000;28:217-26. https://doi.org/10.1142/S0192415X0000026X
  34. Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cell Signal. 2001;13:85-94. https://doi.org/10.1016/S0898-6568(00)00149-2
  35. Wogensen L, Jensen M, Svensson P, Worsaae H, Welinder B, Nerup J. Pancreatic beta-cell function and interleukin-$1{\beta}$ in plasma during the acute phase response in patients with major burn injuries. Eur J Clin Invest. 1993;23:311-9. https://doi.org/10.1111/j.1365-2362.1993.tb00780.x
  36. Takabayashi T, Shimizu S, Clark BD, Beinborn M, Burke JF, Gelfand JA. Interleukin-1 upregulates anaphylatoxin receptors on mononuclear cells. Surgery. 2004;135:544-54. https://doi.org/10.1016/j.surg.2003.09.010
  37. Noh MS, Ha JY, Lee CH, Lee WY, Lee SH, Lee JJ. Inhibitory activities of natural products on lipopolysaccharide induced prostaglandin production in mouse macrophages. Yakhak Hoeji. 1998;42:558-66.
  38. Surh YJ. Role of Cyclooxygenase-2 in Carcimogenesis and Its Selective Inhibition for Cancer Chemoprevention. Molecules and cells. 2001;13:8-17.
  39. Lee AK, Sung SH, Kim YC, Kim SG. Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-$\alpha$ and COX-2 expression by sauchinone effects on I-${\kappa}B{\alpha}$ phosphorylation, C/EBP and AP-1 activation. Brit J Pharmacol. 2003;139:11-20. https://doi.org/10.1038/sj.bjp.0705231
  40. Palombella VJ, Rando OJ, Goldberg AL, Maniatis T. The ubiquitinproteasome pathway is required for processing the NF-${\kappa}B1$ precursor protein and the activation of NF-${\kappa}B$. Cell. 1996;78:773-85.

피인용 문헌

  1. 죽엽 열수추출물의 염증억제 효과 vol.24, pp.4, 2013, https://doi.org/10.14374/hfs.2016.24.4.259