Effect of Foeniculum Vulgare extract on inflammatory response in lipopolysaccharide exposed rats

회향(茴香) 추출물이 LPS를 처리한 Rat의 염증반응에 미치는 영향

  • Published : 2013.04.30


Objectives : This study was performed to investigate the effects of Foeniculum Vulgare(FV) extract on the anti-inflammatory of lipopolysaccharide(LPS) exposed rats. Methods : We divided LPS exposed Sprague-Dawley rats into 4 groups. They were control group, feed with 100 mg/kg, 200 mg/kg, 300 mg/kg FV groups. They were administered for 6 weeks. We measured the concentration of plasma interleukin-1${\beta}$(IL-1${\beta}$), plasma interleukin-6(IL-6), plasma tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), plasma interleukin-10(IL-10), the concentration of liver IL-1${\beta}$, IL-6, TNF-${\alpha}$ and IL-10. Results : 1. Plasma IL-1${\beta}$, plasma IL-6 and plasma TNF-${\alpha}$ concentration increased rapidly at 2hours after LPS injection and maintained high levels at 5hours after LPS injection. The concentration of these cytokines in the FV extract groups showed lower values than control group(P<0.05). 2. The concentration of Plasma IL-10 in FV extract groups showed higher values than control group at all times(P<0.05). 3. The concentration of liver IL-1${\beta}$ and IL-6 in FV extract groups showed lower values than control group(P<0.05). The concentration of liver TNF-${\alpha}$ in FV extract groups showed a tendency to decrease and that of liver IL-10 in FV extract groups showed a tendency to increase; however, these values showed no significantly different. Conclusions : In inflammatory response by LPS derivation, the FV gives positive effect.


Foeniculum Vulgare;Lipopolysaccharide;Inflammatory response;Cytokine


  1. Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy of immune-mediated diseases: basic and clinical correlates. Annals of Intern Medicine. 1992;119(12):1198-208.
  2. Tracy KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC. Anti-cachectin/TNF monoclonal antibodies prevent septic shock dmuring lethal bacteraemia. Nature. 1987;330(6149):662-4. https://doi.org/10.1038/330662a0
  3. Pender SL, Breese EJ, Gunther U. Suppression of T-cell-mediated injury in human gut by interleukin 10: Role of matrix metalloproteinases. Gastroenterology. 1998;115(3):573-83. https://doi.org/10.1016/S0016-5085(98)70136-2
  4. Schotte H, Schluter B, Willeke P, Mickholz E, Schora A, Domschke W, Gaubitz M. Long-term treatment with etanercept significantly reduces the number of pro-inflammatory cytokine secteting peripheral blood mononuclear cells in patients with rheumatoid arthritis. Rheumatology. 2004;43(8):112-8. https://doi.org/10.1093/rheumatology/keg434
  5. Busam KJ, Bauer TM, Bauer J, Gerok W, Decker K. Interleukin-6 release by rat liver macrophages. Journal of hepatology. 1990;11(3):367-73. https://doi.org/10.1016/0168-8278(90)90223-E
  6. Simpson KJ, Lukacs NW, Colletti L, Strieter RM, Kunkel SL. Cytokines and the liver. Journal of hepatology. 1997;27(6):1120-32. https://doi.org/10.1016/S0168-8278(97)80160-2
  7. Hill DB, Marsano LS, McClain CJ. Increased plasma interleukin-8 concentrations in alcoholic hepatitis. Hepatology. 1993;18(3):576-80. https://doi.org/10.1002/hep.1840180316
  8. Huang YS, Chan CY, Wu JC, Pai CH, Chao Y, Lee SD. Serum levels of interleukin-8 in alcoholic liver disease: relationship with disease stage, biochemical parameters and survival. Journal of hepatology. 1996;24(4):377-84. https://doi.org/10.1016/S0168-8278(96)80156-5
  9. Louis H, LeMoine O, Peny MO, Quertinmont E, Fokan D, Goldman M. Production and role of interleukin-10 in concanavalin Ainduced hepatitis in mice. Hepatology. 1997;25(6):1382-9. https://doi.org/10.1002/hep.510250614
  10. Thompson KC, Trowern A, Fowell A, Marathe M, Haycock C, Arthur MJP. Primary rat and mouse hepatic stellate cells express the macrophage inhibitor cytokine interleukin-10 during the course of activation in vitro. Hepatology. 1998;28(6):1518-24. https://doi.org/10.1002/hep.510280611
  11. Hibi M, Nakajima K, Hirano T. IL-6 cytokine family and signal transduction: a model of the cytokine system. Journal of molecular medicine. 1996;74(1):1-12. https://doi.org/10.1007/BF00202068
  12. Hirano T, Matsuda T, Nakajima K. Signal transduction through gp130 that is shared among the receptors for the interleukin 6 related cytokine subfamily. Stem Cells. 1994;12(3):262-77. https://doi.org/10.1002/stem.5530120303
  13. Chamulitrat W, Blazka ME, Jorden SJ, Luster MI, Mason RP. Tumor necrosis factor-${\alpha}$ and nitric oxide production in endotoxin-primed rats administered carbon tetrachloride. Life Sci. 1995;24:2273-80.
  14. Harbrecht BG, DiSilvio M, Demetris AJ, Simmons RL, Billiar TR. Tumor necrosis factor-${\alpha}$ regulates in vivo nitric oxide synthesis and induces liver injury during endotoxemia. Hepatology. 1994;20:1055-60. https://doi.org/10.1002/hep.1840200439
  15. Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 6th edition. Philadelphia:W.B. Saunders. 2007:354.
  16. Hamada E, Nishida T, Uchiyama Y, Nakamura J, Isihara K, Kazuo H. Activation of Kupffer cells and caspases-3 involved in rat hepatocyte apoptosis induced by endotoxin. Journal of hepatology. 1999;30(5):807-18. https://doi.org/10.1016/S0168-8278(99)80133-0
  17. Briscoe DM, Cotran RS, Pober JS. Effect of tumor necrosis factor, lipopolysaccharide, and IL-4 on the expression of vascular cell adhesion molecule-1 in vivo: correlation with CD3+T cell infiltrataion. Official journal of the American Association of Immunologists. 1992;149(9):2954-60.
  18. Gamble JR, Harlan JM, Klebanoff SJ, Vadas MA. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proceedings of the National Academy of Sciences of the United States of America. 1985;82(24):8667-71. https://doi.org/10.1073/pnas.82.24.8667
  19. Barton CC, Barton EX, Ganey PE, Kunkel SL, Roth RA. Bacterial lipopolysaccharide enhances aflatoxin $B_1$ hepatotoxicity in rats by a mechanism that depends on tumor necrosis factor-${\alpha}$. Hepatology. 2001;33:66-73. https://doi.org/10.1053/jhep.2001.20643
  20. 변부형. Raw 264.7 cell에서 차가 버섯 에탄올 추출물이 Cytokine 발현에 미치는 영향. 대한본초학회지. 2005;20(2):55-60.
  21. Seo WG. Inhibitory effects of methanol extract of Cyperus rotundus rhizomes on nitric oxide and superoxide productions by murine macrophage cell line, RAW 264.7 cells. Journal of Ethnopharmacology. 2001;76(1):59-64. https://doi.org/10.1016/S0378-8741(01)00221-5
  22. 신민교. 임상본초학. 서울:영림사. 2000:305-6.
  23. 안덕균. 원색한국본초도감. 서울:교학사. 1998:446.
  24. Oktay M, Gulcin I, Kufrevioglu OI. Determination of vitro anti-oxidant activity of funnel(Foeniculum vulgare)seed extracts. Food Science and Technology. 2003;36(2):263-71.
  25. 이장천, 이은, 오황, 윤호석, 하태광, 홍은희, 이영철. 회향의 간장기능 회복효과. 대한본초학회지. 2007;22(4):213-8.
  26. 최은미, 구성자. LPS로 자극한 RAW264.7 대식세포주에서 회향 추출물에 의한 염증성 매 개물의 생성 억제. 한국식품조리과학회지. 2004;20(5):505-10.
  27. 김종대, 황호연, 최영수, 정병희, 임병우. 회향 추출물의 급여가 자연발증 고혈압 쥐의 혈압에 미치는 영향. 한국약용작물학회 춘계학술발표회. 2007;161-2.
  28. 이재준, 최미숙, 정정수, 최병대. 식이 제한이 흰쥐 지방조직의 Lipoprotein Lipase활성과 지방합성에 미치는 영향. 운동영양학회지. 2003;7(2):135-41.
  29. 김현제. 한의학사전. 서울:성보사. 1988:194.
  30. 문류모. stress에 관한 문헌적 고찰. 동의신경정신과학회지. 1991;2(1):38-50.
  31. 최유진, 노정두. 당귀약침액이 대식세포에서 산화질소(NO) 및 프로스타글란딘(Prostaglandin) 생성에 미치는 영향. 대한약침학회지. 2011;14(3):81-90.
  32. 김형석, 노정두. 육계약침액이 LPS로 유도된 대식세포의 염증반응에 미치는 영향. 대한침구학회지. 2012;29(1):15-24.
  33. Marriot JB, Westby M, Cookson S, Guckian M, Goodbourn S, Muller G. CC-3052: a water-soluble analog of thalidomide and potent inhibitor of activation-induced TNF-${\alpha}$ production. Journal of Immunology. 1998;161(8):4236-43.
  34. Willeaume V, Kruys V, Mijatovic T, Huez G. Tumor necrosis factor-alpha production induced by viruses and by lipopolysaccharides in macrophages: similarities and differences. Journal of inflammation. 1996;46(1):1-12.
  35. Funk CD, Frunk LB, Kennedy ME, Pong AS. Fitzgerald GA. Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. The FASEB journal. 1991;5(9):2304-12.
  36. Mathiak G, Grass G, Herzmann T, Luebke T, Cu-Zetina C, Boehm SA. Capase-1-inhibitor ac-YVAD-cmk reduces LPS-lethality in rats without affecting haematology or cytokine responses. British journal of pharmacology. 2000;131(3):383-6. https://doi.org/10.1038/sj.bjp.0703629
  37. Eduard FM, Martha SMR, Victor PA, Pablo M. Immunomodulatory effects of thalidomide analogs on LPS-induced plasma and hepatic cytokines in the rat. Biochemical pharmacology. 2004;68(7):1321-9. https://doi.org/10.1016/j.bcp.2004.06.018
  38. Benvenistem EN. Cytokine actions in the central nervous system. Cytokine & Growth Factor. 1998;9(3-4):259-75. https://doi.org/10.1016/S1359-6101(98)00015-X
  39. Murphy S. Production of nitric oxide by glial cells: regulation and potential roles in the CNS. Glia. 2000;29(1):1-13. https://doi.org/10.1002/(SICI)1098-1136(20000101)29:1<1::AID-GLIA1>3.0.CO;2-N
  40. Abbas AK. Cellular and Molecular Immunology. 6th edition. Philadelphia:Saunders Elsevier. 2006:75-97.
  41. 윤현정, 허숙경, 이효승, 김창현, 김병완, 박선동. 마우스 대식세포인 RAW 264.7 세포에서 인진호탕(茵陳蒿湯)의 항염증 효과. 대한본초학회지. 2008;23(2):169-78.
  42. Rabson A, Roitt IM, Delves PJ. Really essential medical immunology. Oxford:Blackwell. 2005:1-14.
  43. Chao CY, Yeh SL, Lin MT, Chen WJ. Effects of parenteral infusion with fish-oil or safflower-oil emulsion on hepatic lipids, plasma amino acids, and inflammatory mediators in septic rats. Nutrition. 2000;16:284-8. https://doi.org/10.1016/S0899-9007(99)00299-3