대한본초학회지 (The Korea Journal of Herbology)

  • 제25권4호
  • /
  • Pages.103-112
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  • 2010
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  • 1229-1765(pISSN)
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  • 2288-7199(eISSN)
대한본초학회 (The Korea Association of Herbology)
권호 표지
DOI QR코드

DOI QR Code

마우스 대식세포에서 도기탕 (導氣湯) 메탄올 추출물의 항산화 및 항염증 효과

Anti-oxidative and anti-inflammatory effect of Do-Ki-Tang methanol extract in mouse macrophage cells

  • 김동완 (동국대학교 한의과대학 방제학교실) ;
  • 윤현정 (동국대학교 한의과대학 방제학교실) ;
  • 허준영 (동국대학교 한의과대학 방제학교실) ;
  • 김태훈 (동국대학교 한의과대학 방제학교실) ;
  • 조현진 (동국대학교 한의과대학 방제학교실) ;
  • 박선동 (동국대학교 한의과대학 방제학교실)
  • Kim, Dong-Wan (Department of Prescriptionology, Collage of Oriental Medicine, Dongguk University) ;
  • Yun, Hyun-Jeong (Department of Prescriptionology, Collage of Oriental Medicine, Dongguk University) ;
  • Heo, Jun-Young (Department of Prescriptionology, Collage of Oriental Medicine, Dongguk University) ;
  • Kim, Tae-Hoon (Department of Prescriptionology, Collage of Oriental Medicine, Dongguk University) ;
  • Cho, Hyun-Jin (Department of Prescriptionology, Collage of Oriental Medicine, Dongguk University) ;
  • Park, Sun-Dong (Department of Prescriptionology, Collage of Oriental Medicine, Dongguk University)
  • 투고 : 2010.11.11
  • 심사 : 2010.12.15
  • 발행 : 2010.12.30
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초록

Objective : The aim of this study was to determine whether methanol extract of Do-Ki-Tang (DKT) inhibit free radical generation and production of nitrite an index of NO, $PGE_2$, iNOS, COX-2 and pro-inflammatory cytokines such as TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods : Cytotoxic activity of extract on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. The expression level of inflammatory response-related proteins was confirmed by western blot. The production of proinflammatory cytokines was measured by ELISA. Results : Our results indicated that DKT scavenged DPPH radical and nitric oxide in vitro. Moreover, DKT significantly inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 formation in macrophages. Furthermore, DKT treatment also blocked LPS-induced intracellular ROS production and the activation of NF-${\kappa}B$ and MAPKs. Conclusion : Our data suggest that the anti-inflammatory effect of DKT is mediated through down-modulation of pro-inflammatory mediators and cytokines by blocking the signaling pathways of NF-${\kappa}B$ and MAPKs. These inhibitory effects by DKT represent a potential therapeutic approach to the treatment of inflammatory diseases.

키워드

참고문헌

  1. 金相贊 外. 方劑學. 서울 : 영림사. 2003 : 389-90.
  2. Park SN. Skin aging and antioxidants. J Korean Soc Cosmetic Chem. 1997 ; 23 : 75-132.
  3. Bunn HF, Poyton RO. Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev. 1996 ; 76(3) : 839-85.
  4. Bhattacharyya A, Pathak S, Kundu M, Basu J. Mitogen-activated protein kinases regulate Mycobacterium avium-induced tumor necrosis factor-alpha release from macrophages. FEMS Immunol Med Microbiol. 2002 ; 34(1) : 73-80.
  5. Kaplanski G, Marin V, Montero-Julian F, Mantovani A, Farnarier C. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol. 2003 ; 24(1) : 25-9. https://doi.org/10.1016/S1471-4906(02)00013-3
  6. Feng GJ, Goodridge HS, Harnett MM, Wei XQ, Nikolaev AV, Higson AP, Liew FY. Extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases differentially regulate the lipopolysaccharide -mediated induction of inducible nitric oxide synthase and IL-12 in macrophages: Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase. J Immunol. 1999 ; 163(12) : 6403-12.
  7. Zhang B, Wang ZF, Tang MZ, Shi YL. Growth inhibition and apoptosis-induced effect on human cancer cells of toosendanin, a triterpenoid derivative from chinese traditional medicine. Invest New Drugs. 2005 ; 23(6) : 547-53. https://doi.org/10.1007/s10637-005-0909-5
  8. Xie F, Zhang M, Zhang CF, Wang ZT, Yu BY, Kou JP. Anti-inflammatory and analgesic activities of ethanolic extract and two limonoids from Melia toosendan fruit. J Ethnopharmacol. 2008 ; 117(3) : 463-6. https://doi.org/10.1016/j.jep.2008.02.025
  9. Zhang Y, Qi X, Gong L, Li Y, Liu L, Xue X, Xiao Y, Wu X, Ren J. Roles of reactive oxygen species and MAP kinases in the primary rat hepatocytes death induced by toosendanin. Toxicology. 2008 ; 249(1) : 62-8. https://doi.org/10.1016/j.tox.2008.04.005
  10. Yuen MF, Tam S, Fung J, Wong DK, Wong BC, Lai CL. Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: a 1-year prospective study. Aliment Pharmacol Ther. 2006 ; 24(8) : 1179-86. https://doi.org/10.1111/j.1365-2036.2006.03111.x
  11. Gokhale AB, Damre AS, Kulkami KR, Saraf MN. Preliminary evaluation of anti-inflammatory and anti-arthritic activity of S. lappa, A. speciosa and A. aspera. Phytomedicine. 2002 ; 9(5) : 433-7. https://doi.org/10.1078/09447110260571689
  12. Zhao F, Xu H, He EQ, Jiang YT, Liu K. Inhibitory effects of sesquiterpenes from Saussurea lappa on the overproduction of nitric oxide and TNF-alpha release in LPS-activated macrophages. J Asian Nat Prod Res. 2008 ; 10(11-12) : 1045-53. https://doi.org/10.1080/10286020802274037
  13. Ko SG, Kim HP, Jin DH, Bae HS, Kim SH, Park CH, Lee JW. Saussurea lappa induces G2-growth arrest and apoptosis in AGS gastric cancer cells. Cancer Lett. 2005 ; 220(1) : 11-9. https://doi.org/10.1016/j.canlet.2004.06.026
  14. Chen HC, Chou CK, Lee SD, Wang JC, Yeh SF. Active compounds from Saussurea lappa Clarks that suppress hepatitis B virus surface antigen gene expression in human hepatoma cells. Antiviral Res. 1995 ; 27(1-2) : 99-109. https://doi.org/10.1016/0166-3542(94)00083-K
  15. Jeong GS, Pae HO, Jeong SO, Kim YC, Kwon TO, Lee HS, Kim NS, Park SD, Chung HT. The alpha-methylene-gamma-butyrolactone moiety in dehydrocostus lactone is responsible for cytoprotective heme oxygenase-1 expression through activation of the nuclear factor E2-related factor 2 in HepG2 cells. Eur J Pharmacol. 2007 ; 565(1-3) : 37-44. https://doi.org/10.1016/j.ejphar.2007.02.053
  16. Yu HH, Lee JS, Lee KH, Kim KY, You YO. Saussurea lappa inhibits the growth, acid production, adhesion, and water-insoluble glucan synthesis of Streptococcus mutans. J Ethnopharmacol. 2007 ; 111(2) : 413-7. https://doi.org/10.1016/j.jep.2006.12.008
  17. Oberg F, Haseeb A, Ahnfelt M, Ponten F, Westermark B, El-Obeid A. Herbal melanin activates TLR4/NF-kappaB signaling pathway. Phytomedicine. 2009 ; 16(5) : 477-84. https://doi.org/10.1016/j.phymed.2008.10.008
  18. Cemek M, Enginar H, Karaca T, Unak P. In vivo radioprotective effects of Nigella sativa L oil and reduced glutathione against irradiation-induced oxidative injury and number of peripheral blood lymphocytes in rats. Photochem Photobiol. 2006 ; 82(6) : 1691-6. https://doi.org/10.1111/j.1751-1097.2006.tb09832.x
  19. Koka PS, Mondal D, Schultz M, Abdel-Mageed AB, Agrawal KC. Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells: role of reactive oxygen species. Exp Biol Med. 2010 ; 235(6) : 751-60. https://doi.org/10.1258/ebm.2010.009369
  20. Banerjee S, Kaseb AO, Wang Z, Kong D, Mohammad M, Padhye S, Sarkar FH, Mohammad RM Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res. 2009 ; 69(13) : 5575-83. https://doi.org/10.1158/0008-5472.CAN-08-4235
  21. Kokoska L, Havlik J, Valterova I, Sovova H, Sajfrtova M, Jankovska I. Comparison of chemical composition and antibacterial activity of Nigella sativa seed essential oils obtained by different extraction methods. J Food Prot. 2008 ; 71(12) : 2475-80. https://doi.org/10.4315/0362-028X-71.12.2475
  22. El-Naggar T, Gomez-Serranillos MP, Palomino OM, Arce C, Carretero ME.. Nigella sativa L. seed extract modulates the neurotransmitter amino acids release in cultured neurons in vitro. J Biomed Biotechnol. Epub 2010 Jun 16.
  23. Kim BJ, Kim JH, Kim HP, Heo MY. Biological screening of 100 plant extracts for cosmetic use (II): anti-oxidative activity and free radical scavenging activity. Int J Cosmet Sci. 1997 ; 19(6) : 299-307. https://doi.org/10.1111/j.1467-2494.1997.tb00194.x
  24. Xu ML, Li G, Moon DC, Lee CS, Woo MH, Lee ES, Jahng Y, Chang HW, Lee SH, Son JK. Cytotoxicity and DNA topoisomerase inhibitory activity of constituents isolated from the fruits of Evodia officinalis. Arch Pharm Res. 2006 ; 29(7) : 541-7. https://doi.org/10.1007/BF02969262
  25. Ho JN, Lee YH, Lee YD, Jun WJ, Kim HK, Hong BS, Shin DH, Cho HY. Inhibitory effect of Aucubin isolated from Eucommia ulmoides against UVB-induced matrix metalloproteinase-1 production in human skin fibroblasts. Biosci Biotechnol Biochem. 2005 ; 69(11) : 2227-31. https://doi.org/10.1271/bbb.69.2227
  26. Kim ST, Kim JD, Lyu YS, Lee MY, Kang HW. Neuroprotective effect of some plant extracts in cultured CT105-induced PC12 cells. Biol Pharm Bull. 2006 ; 29(10) : 2021-4. https://doi.org/10.1248/bpb.29.2021
  27. Yamahara J, Yamada T, Kitani T, Naitoh Y, Fujimura H. Antianoxic action and active constituents of evodiae fructus. Chem Pharm Bull (Tokyo). 1989 ; 37(7) : 1820-2. https://doi.org/10.1248/cpb.37.1820
  28. Gyamfi MA, Yonamine M, Aniya Y. Free-radical scavenging action of medicinal herbs from Ghana. Gen Pharmacol. 1999 ; 32 : 661-7. https://doi.org/10.1016/S0306-3623(98)00238-9
  29. Sutherland H, Khundkar R, Zolle O, McArdle A, Simpson AW, Jarvis JC Salmons S. A fluorescence-based method for measuring nitric oxide in extracts of skeletal muscle. Nitric Oxide. 2001 ; 5 : 475-81. https://doi.org/10.1006/niox.2001.0374
  30. Desai A, Vyas T, Amiji M. Cytotoxicity and apopotosis enhancement in brain tumor cells upon coadministration of paclitaxel and ceramide in nanoemulsion formulations. J Pharm Sci. 2008 ; 97(7) : 2745-56. https://doi.org/10.1002/jps.21182
  31. Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med. 1999;27:612-6. https://doi.org/10.1016/S0891-5849(99)00107-0
  32. Rong Y, Geng Z, Lau BH. Ginko biloba attenuates oxidative stress in macrophages and endothelial cells. Free Radic Biol Med. 1996 ; 20 : 121-7. https://doi.org/10.1016/0891-5849(95)02016-0
  33. Wang S, Chen Y, He D, He L, Yang Y, Chen J, Wang X. Inhibition of vascular smooth muscle cell proliferation by serum from rats treated orally with Gastrodia and Uncaria decoction, a traditional Chinese formulation. J Ethnopharmacol. 2007 ; 114(3) : 458-62. https://doi.org/10.1016/j.jep.2007.08.039
  34. Liang YC, Huang YT, Tsai SH, Lin-Shiau SY, Chen CF, Lin JK. Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis. 1999 ; 20(10) : 1945-52. https://doi.org/10.1093/carcin/20.10.1945
  35. Hinz B, Brune K. Cyclooxygenase-2--10 years later. J Pharmacol Exp Ther. 2002 ; 300(2) : 367-75. https://doi.org/10.1124/jpet.300.2.367
  36. Abul KA, Andrew HL, Shiv P. 세포분자면역학, 6판. 서울 : 이퍼블릭. 2008 : 271-96.
  37. Moynagh PN. The NF-kappaB pathway. J Cell Sci. 2005 ; 118 : 4589-92. https://doi.org/10.1242/jcs.02579
  38. Ci X, Liang X, Luo G, Yu Q, Li H, Wang D, Li R, Deng X. Regulation of inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells by2''-hydroxy-3''-en-anhydroicaritin involves down-regulation of NF-kappa B and MAPK expression. Int Immunopharmacol. 2010 ; 10(9) : 995-1002. https://doi.org/10.1016/j.intimp.2010.04.015