Suppression of Inflammatory Macrophage Responese by Glycyrrhiza Uralensis Herbal Acupuncture Extract

감초 약침액이 대식세포주에서 항염증효과에 미치는 영향

  • Bak, Jong-Phil (The Clinical Trial Center for Bio-Industry Se-Myung University) ;
  • Son, Jeong-Hyun (The Clinical Trial Center for Bio-Industry Se-Myung University) ;
  • Kim, Yong-Min (The Clinical Trial Center for Bio-Industry Se-Myung University) ;
  • Lee, Eun-Yong (Dept. of Acupuncture & Moxibustion, College of Korean Medicine, Se-Myung University) ;
  • Leem, Kang-Hyun (Dept. of Herbology, College of Korean Medicine, Se-Myung University) ;
  • Kim, Ee-Hwa (Dept. of Meridian & Acupoint, College of Korean Medicine, The Clinical Trial Center for Bio-Industry Se-Myung University)
  • 박종필 (세명대학교 한방바이오산업 임상지원센터) ;
  • 손정현 (세명대학교 한방바이오산업 임상지원센터) ;
  • 김용민 (세명대학교 한방바이오산업 임상지원센터) ;
  • 이은용 (세명대학교 한의과대학 침구학교실) ;
  • 임강현 (세명대학교 한의과대학 본초학교실) ;
  • 김이화 (세명대학교 한의과대학 경락경혈학교실)
  • Received : 2011.11.08
  • Accepted : 2011.12.12
  • Published : 2011.12.27

Abstract

목적 : 본 연구는 감초의 염증에 대한 효과를 연구하였다. 감초의 에탄올 그리고 물로 추출한 두 가지의 약침액을 이용하여 쥐의 대식세포에서 유래한 RAW264.7 세포에 대한 염증 억제효과를 확인하였다. 방법 : Inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2)를 포함한 염증성 단백질의 발현과 extracellular signal-regulated kinase 1/2(ERK1/2) 그리고 phosphorylated ERK1/2 의 발현을 Western blot 으로 확인하였고, PGE2의 발현은 ELISA 로 확인하였다. 결과 : RAW264.7 세포에 감초의 물 혹은 에탄올 추출 약침액을 투여한 결과 투여된 농도에 따라 LPS로 유도된 NO의 생성이 억제되었으며 iNOS, COX-2, 그리고 인산화 ERK1/2 의 발현도 감소되었다. 결론 : 본 실험 결과, 적작약의 물 그리고 에탄올 추출 약침액에 대하여 항염증성 효과가 있음을 확인하였다.

Keywords

References

  1. Lee HD, Song CH. Effect of pharmacopuncture on PCA and secretion of b-hexosaminidase and cytokines in RBL-2H3 cells. Korean J of Acupuncture. 2011 ; 28(3) : 73-83.
  2. Shim SB, Kim NJ, Kim DH. Beta-glucuronidase inhibitory activity and hepatoprotective effect of 18 beta-glycyrrhetinic acid from the rhizomes of Glycyrrhiza uralensis. Planta Med. 2000 ; 66(1) : 40-3. https://doi.org/10.1055/s-2000-11109
  3. Wang H, Chang B, Wang B. [The effect of herbal medicine including astragalus membranaceus (fisch) bge, codonpsis pilosula and glycyrrhiza uralensis fisch on airway responsiveness]. Zhonghua Jie He He Hu Xi Za Zhi. 1998 ; 21(5) : 287-8.
  4. Shin EM, Zhou HY, Guo LY, Kim JA, Lee SH, Merfort I et al. Anti-inflammatory effects of glycyrol isolated from Glycyrrhiza uralensis in LPS-stimulated RAW264.7 macrophages. Int Immunopharmacol. 2008 ; 8(11) : 1524-32. https://doi.org/10.1016/j.intimp.2008.06.008
  5. Hibbs JB, Jr. Taintor RR, Vavrin Z. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science. 1987 ; 235(4787) : 473-6. https://doi.org/10.1126/science.2432665
  6. Kock A, Schwarz T, Kirnbauer R, Urbanski A, Perry P, Ansel JC et al. Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light. J Exp Med. 1990 ; 172(6) : 1609-14. https://doi.org/10.1084/jem.172.6.1609
  7. Lawrence T, Willoughby DA, Gilroy DW. Antiinflammatory lipid mediators and insights into the resolution of inflammation. Nat Rev Immunol. 2002 ; 2(10) : 787-95. https://doi.org/10.1038/nri915
  8. Lowenstein CJ, Hill SL, Lafond-Walker A, Wu J, Allen G, Landavere M et al. Nitric oxide inhibits viral replication in murine myocarditis. J Clin Invest. 1996 ; 97(8) : 1837-43. https://doi.org/10.1172/JCI118613
  9. Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 ; 333(6174) : 664-6. https://doi.org/10.1038/333664a0
  10. Adams DO, Hamilton TA. The cell biology of macrophage activation. Annu Rev Immunol. 1984 ; 2 : 283-318. https://doi.org/10.1146/annurev.iy.02.040184.001435
  11. Aderem A. Phagocytosis and the inflammatory response. J Infect Dis. 2003 ; 187 Suppl 2 : S340-5.
  12. Nathan CF. Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest. 1987 ; 80(6) : 1550-60. https://doi.org/10.1172/JCI113241
  13. Wu GJ, Chen TL, Ueng YF, Chen RM. Ketamine inhibits tumor necrosis factor-alpha and interleukin-6 gene expressions in lipopolysaccharide-stimulated macrophages through suppression of toll-like receptor 4-mediated c-Jun N-terminal kinase phosphorylation and activator protein-1 activation. Toxicol Appl Pharmacol. 2008 ; 228(1) : 105-13. https://doi.org/10.1016/j.taap.2007.11.027
  14. Chan SC, Kim JW, Henderson WR, Jr. Hanifin JM. Altered prostaglandin E2 regulation of cytokine production in atopic dermatitis. J Immunol. 1993 ; 151(6) : 3345-52.
  15. Culbert AA, Skaper SD, Howlett DR, Evans NA, Facci L, Soden PE et al. MAPK-activated protein kinase 2 deficiency in microglia inhibits pro-inflammatory mediator release and resultant neurotoxicity. Relevance to neuroinflammation in a transgenic mouse model of Alzheimer disease. J Biol Chem. 2006 ; 281(33) : 23658-67. https://doi.org/10.1074/jbc.M513646200
  16. Mahut B, Delclaux C, Tillie-Leblond I, Gosset P, Delacourt C, Zerah-Lancner F et al. Both inflammation and remodeling influence nitric oxide output in children with refractory asthma. J Allergy Clin Immunol. 2004 ; 113(2) : 252-6. https://doi.org/10.1016/j.jaci.2003.10.038
  17. Puckett JL, Taylor RW, Leu SY, Guijon OL, Aledia AS, Galant SP et al. An elevated bronchodilator response predicts large airway inflammation in mild asthma. Pediatr Pulmonol. 2010 ; 45(2) : 174-81. https://doi.org/10.1002/ppul.21172
  18. Schmidt HH, Walter U. NO at work. Cell. 1994 ; 78(6) : 919-25. https://doi.org/10.1016/0092-8674(94)90267-4
  19. Bredt DS, Snyder SH. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci USA. 1989 ; 86(22) : 9030-3. https://doi.org/10.1073/pnas.86.22.9030
  20. Palmer RM, Moncada S. A novel citrullineforming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun. 1989 ; 158(1) : 348-52. https://doi.org/10.1016/S0006-291X(89)80219-0
  21. Sessa WC. The nitric oxide synthase family of proteins. J Vasc Res. 1994 ; 31(3) : 131-43. https://doi.org/10.1159/000159039
  22. Bredt DS, Snyder SH. Transient nitric oxide synthase neurons in embryonic cerebral cortical plate, sensory ganglia, and olfactory epithelium. Neuron. 1994 ; 13(2) : 301-13. https://doi.org/10.1016/0896-6273(94)90348-4
  23. Adams V, Yu J, Mobius-Winkler S, Linke A, Weigl C, Hilbrich L et al. Increased inducible nitric oxide synthase in skeletal muscle biopsies from patients with chronic heart failure. Biochem Mol Med. 1997 ; 61(2) : 152-60. https://doi.org/10.1006/bmme.1997.2598
  24. Torres SH, De Sanctis JB, de LBM, Hernandez N, Finol HJ. Inflammation and nitric oxide production in skeletal muscle of type 2 diabetic patients. J Endocrinol. 2004 ; 181(3) : 419-27. https://doi.org/10.1677/joe.0.1810419
  25. Skidgel RA, Gao XP, Brovkovych V, Rahman A, Jho D, Predescu S et al. Nitric oxide stimulates macrophage inflammatory protein-2 expression in sepsis. J Immunol. 2002 ; 15;169(4) : 2093-101.
  26. Lipton SA, Choi YB, Pan ZH, Lei SZ, Chen HS, Sucher NJ et al. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitrosocompounds. Nature. 1993 ; 364(6438) : 626-32. https://doi.org/10.1038/364626a0
  27. Wu KK. Cyclooxygenase 2 induction: molecular mechanism and pathophysiologic roles. J Lab Clin Med. 1996 ; 128(3) : 242-5. https://doi.org/10.1016/S0022-2143(96)90023-2
  28. Tetsuka T, Daphna-Iken D, Miller BW, Guan Z, Baier LD, Morrison AR. Nitric oxide amplifies interleukin 1-induced cyclooxygenase-2 expression in rat mesangial cells. J Clin Invest. 1996 ; 97(9) : 2051-6. https://doi.org/10.1172/JCI118641
  29. Williams CS, DuBois RN. Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol. 1996 ; 270(3 Pt 1) : G393-400.
  30. Schneider A, Stahl RA. Cyclooxygenase-2 (COX-2) and the kidney: current status and potential perspectives. Nephrol Dial Transplant. 1998 ; 13(1) : 10-2. https://doi.org/10.1093/ndt/13.1.10
  31. McGinty A, Foschi M, Chang YW, Han J, Dunn MJ, Sorokin A. Induction of prostaglandin endoperoxide synthase 2 by mitogen-activated protein kinase cascades. Biochem J. 2000 ; 352 Pt 2 : 419-24.
  32. Clement-Kruzel S, Hwang SA, Kruzel MC, Dasgupta A, Actor JK. Immune modulation of macrophage pro-inflammatory response by goldenseal and Astragalus extracts. J Med Food. 2008 ; 11(3) : 493-8. https://doi.org/10.1089/jmf.2008.0044
  33. Jung HW, Mahesh R, Park JH, Boo YC, Park KM, Park YK. Bisabolangelone isolated from Ostericum koreanum inhibits the production of inflammatory mediators by down-regulation of NF-kappaB and ERK MAP kinase activity in LPS-stimulated RAW264.7 cells. Int Immunopharmacol. 2010 ; 10(2) : 155-62. https://doi.org/10.1016/j.intimp.2009.10.010
  34. Calderon-Garciduenas L, Reed W, Maronpot RR, Henriquez-Roldan C, Delgado-Chavez R, Calderon-Garciduenas Aet al. Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution. Toxicol Pathol. 2004 ; 32(6) : 650-8. https://doi.org/10.1080/01926230490520232
  35. Grunblatt E, Mandel S, Youdim MB. Neuroprotective strategies in Parkinson's disease using the models of 6-hydroxydopamine and MPTP. Ann N Y Acad Sci. 2000 ; 899 : 262-73.
  36. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 ; 81(2) : 741-66.
  37. Jeremy JY, Rowe D, Emsley AM, Newby AC. Nitric oxide and the proliferation of vascular smooth muscle cells. Cardiovasc Res. 1999 ; 43(3) : 580-94. https://doi.org/10.1016/S0008-6363(99)00171-6
  38. Ridnour LA, Thomas DD, Donzelli S, Espey MG, Roberts DD, Wink DA et al. The biphasic nature of nitric oxide responses in tumor biology. Antioxid Redox Signal. 2006 ; 8(7-8) : 1329-37. https://doi.org/10.1089/ars.2006.8.1329
  39. Rodriguez-Barbero A, Dorado F, Velasco S, Pandiella A, Banas B, Lopez-Novoa JM. TGF-beta1 induces COX-2 expression and PGE2 synthesis through MAPK and PI3K pathways in human mesangial cells. Kidney Int. 2006 ; 70(5) : 901-9. https://doi.org/10.1038/sj.ki.5001626