Inhibitory Effect of Stephanniae Tetrandrae Radix Extract on $TNF-{\alpha}$, $IL-1{\beta}$, IL-6 and Nitric Oxide Production in Lipopolysaccharide - Activated RAW 264.7 Cells

방기(防己) 추출물이 LPS로 유도된 Raw 264.7 cell에서의 $TNF-{\alpha}$, $IL-1{\beta}$, IL-6 및 Nitric Oxide Production에 미치는 영향

  • 김대희 (대구한의대학교 한의과대학) ;
  • 이종록 (대구한의대학교 한의과대학) ;
  • 변성희 (대구한의대학교 한의과대학) ;
  • 신상우 (대구한의대학교 한의과대학) ;
  • 권영규 (대구한의대학교 한의과대학) ;
  • 김상찬 (대구한의대학교 한의과대학)
  • Published : 2006.08.25

Abstract

Tetrandra is the root of Stephania tetrandra 5. Moore (family Menispermaceae), or of Aristolochia frangchi Wu (family Aristolochiaceae). It is a Differ-flavored and cold-property herb acting on the urinary bladder, kidney and spleen meridiands. Known biological effects of this herb are expelling wind to relieve pain and inducing diuresis to alleviate edema. This herb also has anti-inflammatory and anti-hypersensitivity actions. Recent studies have shown that Stephanniae Tetrandrae Radix has antimicrobial effects, namely, a protective effect on acute renal failure induce by gentamicin sulfate and a suppressive effect against clostridium perfringes. However, there is a lack of studies concerning the immunological activities of this herb. The present study was conducted to evaluate the immunological activities of Stephanniae Tetrandrae Radix on the regulatory mechanisms of cytokines and nitric oxide (NO) in Raw 264.7 cells. Cell viability was measured by MTT assay after the treatment of Stephanniae Tetrandrae Radix extract (STRE) and NO production was monitored by measuring the nitrite content in culture medium. COX-2 and iNOS were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidences that STRE inhibited the production of nitrite and nitrate (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta})$ and interleukin-6 (IL-6) in Raw 264.7 cells activated with lipopolysaccharide (LPS). These findings showed that STRE could produce some anti-inflammatory effects which might play a role in adjunctive therapy in Gram-negative bacterial infections.

Keywords

References

  1. Lee, Y.S., Kim, H.S., Kim, S.K., Kim, S.D. IL-6 mRNA Expression in Mouse Peritoneal Macrophages and NIH3T3 Fibroblasts in Response to Candida albicans. J Microbiol Biotechnol. 10, 8-15, 2000
  2. 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. 144, 1425-1431, 1990
  3. McDaniel, M.L., Kwon, G., Hill, J.R., Marshall, C.A., Corbett, J.A. Cytokines and nitric oxides in islet inflammation and diabetes. Proc Soc Exp Biol Med. 211, 24-32, 1996
  4. Corbett, J.A., Mac Daniel, M.L. Intraislet release of interleukin-1 inhibits beta cell function by inducing beta cell expression of inducible nitric oxide syntheses. J Exp Med. 181, 559-568, 1995 https://doi.org/10.1084/jem.181.2.559
  5. Cetkovic-Cvrlje, M., Eizirik, D.L. TNF and IFN$\gamma$ potentiate the deleterious effects of IL-1$\beta$ on mouse pancreatic islets mainly via generation of nitric oxide. Cytokine 6,399-406, 1994 https://doi.org/10.1016/1043-4666(94)90064-7
  6. 황광진. 산화질소(Nitric Oxide) 이로운가? 해로운가? : 산화질소의 화학과 응용. 대한화학회지 39, 52-63, 1999
  7. Lee, B.G., Kim, S.H., Zee, O.P., Lee, K.R., Lee, H.Y., Han, J.W., Lee, H.W. Suppression of inducible nitric oxide synthase expression in Raw 264.7 macrophages by two-carboline alkaloids extracted from Melia azedarach. Eur J Pharmacol. 406, 301-309, 2000 https://doi.org/10.1016/S0014-2999(00)00680-4
  8. Seo, W.G., Pae, H.O., Oh, G.S., Chai, K.Y., Kwon, T.O., Yun, Y.G., Kim, N.Y., Chung, H.T. Inhibitory effects of methanol extract of Cyperus rotundus rhizomes on nitric oxide and superoxide production by murine macrophage cell line, Raw 264.7 cells. J Ethnopharmacol. 76, 59-64, 2001 https://doi.org/10.1016/S0378-8741(01)00221-5
  9. 이영선, 한옥경, 신상우, 박종현, 권영규. 향부자 열수추출물의 Nitric oxide 생성 및 iNOS 유전자 발현에 미치는 영향. 동의생리병리학회지 17(3):771-776, 2003
  10. Seo, W.G., Pae, H.O., Oh, G.S., Chai, K.Y., Yun, Y.G., Kwon, T.O., Chung, H.T. Inhibitory effect 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. 5, 21-28, 2000
  11. 장선일, 김형진, 황기명, 배현옥, 윤용갑, 정헌택, 김윤철. 활성화된 설치류 Raw 264.7 대식세포에서 당귀에탄올 추출물의 항염증 효과. 대한한의학방제학회지 10(2):189-197, 2002
  12. 김창민, 신민교, 안덕균, 이경순. 중약대사전. 서울, 도서출판 정담. pp 1983-1992, 1998
  13. 전국한의대 본초학교실. 본초학. 서울, 영림사. pp 264-265, 1992
  14. 임종필. 본초생약학. 서울, 신일상사. pp 159-161, 2003
  15. 정혁상, 이현삼, 원란, 강철훈, 손낙원. 방기(防己)가 백서 중대뇌동맥 폐쇄에 의한 국소뇌허혈 손상에 미치는 보호효과. 대한한의학회지 22(1):10-21, 2001
  16. 김영훈. 류마티스양 관절염에 응용되는 방기(防己)의 효능에 관한 실험적 연구. 동서의학 12, 37-57, 1987
  17. 오상덕, 조동현, 두호경, 안세영. 목통 및 방기전탕액이 Gentamicin Sulfate로 유발된 백서의 급성신부전에 미치는 영향. 경희의학 10(1):13-25, 1994
  18. 신동화, 한지숙, 김문숙. 방기 및 감초의 에탄올 추출물이 Listeria monocytogenes의 증식억제에 미치는 영향. Kor J Food Sci Technol. 26(5):627-632, 1994
  19. 신옥호, 유시승, 이완규, 신현경. 방기 (Sinomenium acutum)의 물추출물이 주요 장내 미생물의 생육에 미치는 영향. Kor J Appl Microbiol Biotechnol. 20(5):491-497, 1992
  20. 신현경, 신옥호, 유시승. 방기 (Sinomenium acutum)의 물추출물이 Clostridia 및 주요장내 세균의 생육에 미치는 영향. '92 한국영양학회 춘계심포지움 및 발표논문 초록집. pp 28-29, 1992
  21. 편세현, 박재현. 방기의 안전성에 관한 연구. 동서의학 24(1): 1-13, 1999
  22. Surh, Y.J. Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review. Food Chem Toxicol. 40(8):1091-1097, 2002 https://doi.org/10.1016/S0278-6915(02)00037-6
  23. Surh, Y.J., Chun, K.S., Cha, H.H., Han, S.S., Keum, Y.S., Park, K.K., Lee, S.S. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res. pp 480-481, 243-268, 2001 https://doi.org/10.1016/S0027-5107(01)00183-X
  24. Lee, A.K., Sung, S.H., Kim, Y.C., Kim, S.G. 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. 139:11-20, 2003 https://doi.org/10.1038/sj.bjp.0705231
  25. Delgado, A.V., McManus, A.T., Chambers, J.P. Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P. Neuropeptides. 37(6):355-361, 2003 https://doi.org/10.1016/j.npep.2003.09.005
  26. Lee, Y.S., Han, O.K., Park, C.W., Yang, C.H., Jeon, T.W., Yoo, W.K., Kim, S.H., Kim, H.J. Pro-inflammatory cytokine gene expression and nitric oxide regulation of aqueous extracted Astragali radix in Raw 264.7 macrophage cells. J Ethnopharmacol. 100(3):289-294, 2005 https://doi.org/10.1016/j.jep.2005.03.009
  27. Vanherweghem, J.L., Abramowicz, D., Tielemans, C., Depierreux, M. Effects of steroids on the progression of renal failure in chronic interstitial renal fibrosis: a pilot study in Chinese herbs nephropathy. Am J Kidney Dis. 27(2):209-215, 1996 https://doi.org/10.1016/S0272-6386(96)90542-9
  28. Vanherweghem, J.L., Depierreux, M., Tielemans, C., Abramowicz, D., Dratwa, M., Jadoul, M., Richard, C., Vandervelde, D., Verbeelen, D., Vanhaelen-Fastre, R. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet. 341(8842):387-391, 1993 https://doi.org/10.1016/0140-6736(93)92984-2
  29. 신영태, 빈기태, 김성숙, 정민수, 이순구, 이강욱 등. 약물에 의한 급성 과민성 간질성신염의 증상. 대한신장학회지 13, 91-99, 1994
  30. Palmer, R.M., Ashton, D.S., Moncada, S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333, 664-666, 1988 https://doi.org/10.1038/333664a0
  31. Kubes, P. Inducible nitric oxide synthase; a little bit of good in all of us. Gut. 47, 6-9, 2000 https://doi.org/10.1136/gut.47.1.6
  32. Chiou, W.F., Chou, C.J., Chen, C.F. Camptothecin suppresses nitric oxide biosynthesis in Raw 264.7 macrophages. Life Sci. 69, 625-635, 2001 https://doi.org/10.1016/S0024-3205(01)01154-7
  33. Kawamata, H., Ochiai, H., Mantani, N., Terasawa, K. Enhanced expression of inducible nitric oxide synthase by Juzen-taiho-to in LPS-activated Raw264.7 cells, a murine macrophage cell line. Am J Chin Med. 28, 217-226, 2000 https://doi.org/10.1142/S0192415X0000026X
  34. Linton, M.F., Fazio, S. Cyclooxygenase-2 and inflammation in atherosclerosis. Curr Opin Pharmacol. 4(2):116-123, 2004 https://doi.org/10.1016/j.coph.2003.12.003
  35. Chen, F., Castranova, V., Shi, X. New insights into the role of nuclear factor-kappaB in cell growth regulation. Am J Pathol. 159(2):387-397, 2001 https://doi.org/10.1016/S0002-9440(10)61708-7
  36. Casey, L.C., Balk, R.A., Bone, R.C. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med. 119, 771-778, 1993 https://doi.org/10.7326/0003-4819-119-8-199310150-00001
  37. Wogensen, L., Jensen, M., Svensson, P., Worsaae, H., Welinder, B., Nerup, J. Pancreatic beta-cell function and interleukin-1b in plasma during the acute phase response in patients with major burn injuries. Eur J Clin Invest. 23, 311-319, 1993 https://doi.org/10.1111/j.1365-2362.1993.tb00780.x
  38. Shito, M., Wakabayashi, G., Ueda, M., Shimazu, M., Shirasugi, N., Endo, M., Mukai, M., Kitajima, M. Interleukin 1 receptor blockade reduces tumor necrosis factor production, tissue injury, and mortality after hepatic ischemia-reperfusion in the rat. Transplantation. 63, 143-148, 1997 https://doi.org/10.1097/00007890-199701150-00026
  39. Takabayashi, T., Shimizu, S., Clark, B.D., Beinborn, M., Burke, J.F., Gelfand, J.A. Interleukin-1 upregulates anaphylatoxin receptors on mononuclear cells. Surgery. 135(5):544-554, 2004 https://doi.org/10.1016/j.surg.2003.09.010