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Anti-atherogenic Effect of Isoflavone through Hypolipidemic, Anti-oxidative and Anti-inflammatory Actions in C57BL/6 Mice

C57BL/6 Mice에서 이소플라본의 지질강하, 항산화, 항염증효과를 통한 항동맥경화 효과

  • Cho, Hye-Yeon (Paik Inje Memorial Clinical Research Institiute, School of Medicine, Inje University) ;
  • Yang, Jeong-Lye (Busan Newport Import Food Inspection Office, Busan Regional Food & Drug Administration) ;
  • Noh, Kyung-Hee (School of Food and Life Sciences, Food Science Institute, and Biohealth Product Research Center, Inje University) ;
  • Kim, Jin-Ju (School of Food and Life Sciences, Food Science Institute, and Biohealth Product Research Center, Inje University) ;
  • Kim, Young-Hwa (School of Food and Life Sciences, Food Science Institute, and Biohealth Product Research Center, Inje University) ;
  • Huh, Kyung-Hye (Major in Molecular & Biomedical Technology, Inje University) ;
  • Song, Young-Sun (School of Food and Life Sciences, Food Science Institute, and Biohealth Product Research Center, Inje University)
  • 조혜연 (인제대학교 의과대학 백인제기념 임상의학연구소) ;
  • 양정례 (부산지방식품의약품안전청 신항수입식품검사소) ;
  • 노경희 (인제대학교 의생명공학대학 식품생명과학부, 식품과학연구소 및 바이오헬스소재연구센터) ;
  • 김진주 (인제대학교 의생명공학대학 식품생명과학부, 식품과학연구소 및 바이오헬스소재연구센터) ;
  • 김영화 (인제대학교 의생명공학대학 식품생명과학부, 식품과학연구소 및 바이오헬스소재연구센터) ;
  • 허경혜 (인제대학교 분자의생명공학과) ;
  • 송영선 (인제대학교 의생명공학대학 식품생명과학부, 식품과학연구소 및 바이오헬스소재연구센터)
  • Published : 2007.03.31

Abstract

This study was carried out to investigate the effect of isoflavone on the atherogenic effect in C57BL/6 mice. C57BL/6 female mice, 5 weeks of age, were fed on chow diets for 2 weeks during adjustment period. Mice weighing approximately $17.9{\pm}0.9\;g$ were divided into 4 groups and were fed on the experimental diets containing isoflavone for 8 weeks. Experimental groups were control (atherogenic diet), IF-10 (atherogenic diet with isoflavone 10 mg/100 g diet), IF-40 (atherogenic diet with isoflavone 40 mg/100 g diet) and IF-100 (atherogenic diet with isoflavone 100 mg/100 g diet). Food efficiency ratio was not different among the experimental groups. Plasma triglyceride (TG) concentrations were lower after 4 weeks in isoflavone supplementation groups than in control group, whereas monocyte chemoattractant protein-1 and thiobarbituric acid reactive substances (TBARS) levels of plasma were significantly (p<0.05) decreased in the isoflavone supplementation groups in a dose dependent manner. Both hepatic TG and cholesterol levels were significantly lowered in IF-100 than control. Hepatic glutathione concentrations were higher in the IF-100 group than in the other groups. Hepatic antioxidant enzyme activities including glutathione-reductase, glutathione-peroxidase, catalase, and Mn-superoxide dismutase were significantly higher in the isoflavone supplemen-tation groups in a dose dependent manner. From the above results, it is concluded that isoflavone may reduce the risk of atherosclerosis via hypolipidemic, anti-oxidative and anti-inflammatory effects.

5주령의 C57BL/6 mice종 암컷 40수를 2주간의 적응기를 거쳐, 평균 체중 $17.9{\pm}0.9\;g$인 실험동물을 완전임의배치로 한 군당 10수씩 4군으로 나누어 실험식이는 동맥경화식이(control)에 이소플라본을 첨가한 실험식이를 각각 8주간 급여하면서 사육하였다. 이소플라본의 첨가량은 식이 100 g 당 10 mg(IF-10)과 40 mg(IF-40) 및 100 mg(IF-100)이 되도록 조정하여 제조하였다. 이소플라본의 섭취는 체중증가량에 영향을 미치지 않는 것으로 나타났으며 식이효율은 각 군 간의 유의적인 차이를 보이지 않았다. 이소플라본 섭취에 의한 혈장 TG 농도는 대조군에 비해 이소플라본을 첨가한 식이를 섭취한 군에서 감소하는 추세를 보였다. 총 콜레스테롤 수준은 모든 실험군에서 증가하는 경향을 보였으나 8주 후의 농도 변화는 대조군에 비해 이소플라본을 첨가한 식이를 섭취한 군에서 감소하는 추세를 보였다. 세포부착물질인 MCP-1과 지질과산화물인 TBARS의 생성량은 이소플라본의 첨가량이 높을수록 현저하게 감소되는 결과를 보여 농도의존적인 효과를 보였다. 간의 TG와 총 콜레스테롤 농도는 이소플라본의 첨가량이 높을수록 감소하는 것으로 나타났으며(p<0.05), 간의 항산화 영양소인 glutathione 함량은 이소플라본을 100 mg 제공한 IF-100에서 유의적으로(p<0.05) 높은 수준을 보였다. 간의 항산화 효소계 활성은 대조군에 비해 이소플라본을 첨가한 식이를 섭취한 군에서 대체로 높게 나타났으며 특히 이소플라본 100 mg을 첨가한 식이를 섭취한 IF-100에서 현저하게 높은 수준을 보였다. 이상의 결과들로 미루어 볼 때 이소플라본의 섭취가 혈장의 중성지방을 저하하고 항염증, 항산화효과를 보여 동맥경화예방에 효과가 있는 물질로 사료된다.

Keywords

References

  1. Maskarinec G, Singh S, Meng L, Franke AA. 1998. Dietary soy intake and urinary isoflavone excretion among women from a miltiethnic population. Cancer Epidemiol Biomarkers Prev 7: 613-619
  2. Schwandt P. 2003. The importance of reaching lipid targets: statins and the prevention of atherosclerosis. Int J Clin Pract 57: 396-404
  3. Anthony MS, Clarkson TB, Willims JK. 1998. Effects of soy isoflavones on atherosclerosis: potential mechanisms. Am J Clin Nutr 68: 1390-1393 https://doi.org/10.1093/ajcn/68.6.1390S
  4. Anthony MS, Clarkson TB, Hughes Jr CL. 1996. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. J Nutr 126: 43-50 https://doi.org/10.1093/jn/126.1.43
  5. Park HS. 2000. Pharmacological treatment of hypertriglyceridemia. J Korean Acad Fam Med 21: 1331-1339
  6. Lee YM, Jung MH, Lee YS, Song JH. 2005. Effect of genistein and soy protein on lipid metabolism in ovariectomized rats. Korean J Nutr 38: 267-278
  7. Lee YS, Jang SY, Kim KO. 2005. Effect of soy isofavone intake on nitrite content and antioxidant enzyme activities in male rats fed high-fat diet. Korean J Nutr 38: 89-95
  8. Bibgham SA, Atkinson C, Liggins J. 1998. Phytoestrogen; where are we now? British J Nutr 79: 393-406 https://doi.org/10.1079/BJN19980068
  9. Ruiz-Larrea MB, Mohan AR, Paganga G. 1997. Antioxidant activity of phytoestrgenic isoflavones. Free Radic Res 26: 63-70 https://doi.org/10.3109/10715769709097785
  10. Wei HC, Wei LH, Frenkel K. 1993. Inhibition of tumor promotor-induced hydrogen peroxide formation in vitro and in vivo by genistein. Nutr Cancer 20: 1-12 https://doi.org/10.1080/01635589309514265
  11. Sekizaki H, Yokosawa R, Chinen C, Adachi H, Yamane Y. 1993. Synthesis of isoflavones and their attracting activity to Aphanomyces euteiches zoospore. Biol Pharm Bull 16: 698-701 https://doi.org/10.1248/bpb.16.698
  12. Kapiotis S, Hermann M, Held I. 1997. Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arterioscler Thromb Vasc Biol 17: 2868-2874 https://doi.org/10.1161/01.ATV.17.11.2868
  13. Kirk EA, Sutherland P, Wang SA. 1998. Dietary isoflavones reduce plasma cholesterol and atherosclerosis in C57BL/6 mice but not LDL receptor-deficient mice. J Nutr 128: 954-959
  14. Picard F, Deshaies Y, Lalonde J. 2000. Effects of the estrogen antagonist EM-652.HCl on energy balance and lipid metabolism in ovariectomized rats. Int J Obes Relat Metab Disord 24: 830-840 https://doi.org/10.1038/sj.ijo.0801240
  15. Roberts CK, Chen AK, Barnard RJ. Effect of a short-term diet and exercise intervention in youth on atherosclerotic risk factors. Atherosclerosis 2006 Oct 18 [Epub ahead of print]
  16. Ito T, Ikeda U. 2003. Infammatory cytokines and cardiovascular disease. Curr Drug Targets Inflamm Allergy 2: 257-265 https://doi.org/10.2174/1568010033484106
  17. Bratus VV, Talaieva TV, Radalovska NV. 1999. The role of a systemic inflammatory process in the atherogenic modification of lipoproteins and the development of hypercholesterolemia. Fiziol Zh 45: 40-49
  18. Kanters E, Pasparakis M, Gijbels M. 2003. Inhibition of NF-${\kappa}$B activation in macrophages increase atherosclerosis in LDL receptor-deficient mice. J Clin Invest 112: 1176-1185 https://doi.org/10.1172/JCI200318580
  19. Kunsch C, Luchoomun J, Grey JY. 2004. Selective inhibition of endothelial and monocyte redox-sensitive genes by AGI-1067: a novel, antioxidant and anti-inflammatory agent. J Pharmacol Exp Ther 308: 820-829 https://doi.org/10.1124/jpet.103.059733
  20. Lee YS, Cheu X, Anderson J. 2001. Physiological concentrations of genistein stimulate the proliferation and protect against free radical-induced oxidative damage of MC3T3- E1 osteoblast-like cells. Nutr Res 21: 1287-1298 https://doi.org/10.1016/S0271-5317(01)00340-2
  21. Rodrdanz E, Ohler S, Tran-Thi QH, Kahl R. 2002. The phytoestrogen daidzein affects the antioxidant enzyme system of rat hepatoma H4IIE cells. J Nutr 132: 370-375
  22. Jang HR. 2002. The effects of soy isoflavone on the factors relating to vascular disease in ovariectomized and hyperlipidemic rats. MS Thesis. Seoul National University, Seoul
  23. Wiseman H, O'Reilly JD, Adlercreutz H, Mallet AI, Bowey EA, Rowland JR, Sanders T. 2000. Isoflavone phytoestrogens consumed in soy decrease F2-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans. Am J Clin Nutr 72: 395-400 https://doi.org/10.1093/ajcn/72.2.395
  24. Jenkins DJ, Kendall CW, Jackson CJ, Connelly PW, Parker T, Faulkner D, Vidgen E, Cunnane SC, Leiter LA, Josse RG. 2002. Effects of high- and low-isoflavone soyfoods on blood lipids, oxidized LDL, homocystein, and blood pressure in hyperlipidemic men and women. Am J Clin Nutr 76: 365-372 https://doi.org/10.1093/ajcn/76.2.365
  25. Liao F, Andalibi A, de Beer FC, Fogelman AM, Lusis AJ. 1993. Genetic control of immflammatory gene induction and NF-$\kappa$B-like transcription factor activation in response to an atherogenic diet in mice. J Clin Invest 91: 2572-2579 https://doi.org/10.1172/JCI116495
  26. Friedewald WT. 1972. Estimation of the concentration of LDL cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18: 499-502
  27. Buege JA, Aust SD. 1978. Microsomal lipid peroxidation. In Methods in Enzymology. Fleischer S, Packer L, eds. Academic press, New York, USA. Vol 52, p 302-306
  28. Folch I, Lees M, Sranley GHS. 1956. A simple method for the isolation and purification of total lipids from animal tissue. J Biochem 223: 497-509
  29. Marklund S, Marklund G. 1974. Involvement of the superoxide anion radical in antioxidant of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47: 469-474 https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
  30. Aebi H. 1984. Catalase in vitro. Methods Enzymol 150: 121-126 https://doi.org/10.1016/S0076-6879(84)05016-3
  31. Tietze F. 1969. Enzymic method for quantitiative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissue. Anal Biochem 27: 502-522 https://doi.org/10.1016/0003-2697(69)90064-5
  32. Lawrence RA, Burk F. 1976. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Comm 71: 952 https://doi.org/10.1016/0006-291X(76)90747-6
  33. Inger C, Bengt M. 1985. Glutathione reductase. In Methods in Enzymology. Fleischer S, Packer L, eds. Academic press, New York, USA. Vol 113, p 484-490
  34. Bradford MM. 1976. A rapid and sensitive method for the quantification of microgram quantities of proteins utilizing the principle of protein-dye binding. Ann Biochem 72: 248-254 https://doi.org/10.1016/0003-2697(76)90527-3
  35. Zhuo XG, Melby MK, Watanabe S. 2004. Soy isoflavone intake lowers serum LDL cholesterol: a meta-analysis of 8 randomized controlled trials in humans. J Nutr 134: 2395-2400
  36. Yeung J, Yu TF. 2003. Effects of isoflavone (soy phyto-estrogen) on serum lipid: a meta-analysis of randomized controlled trials. Nutr J 2: 15-22 https://doi.org/10.1186/1475-2891-2-15
  37. Weggemans RM, Trautwein EA. 2003. Relation between soy-associated isoflavones and LDL and HDL cholesterol concentrations in humans: a meta-analysis. Eur J Clin Nutr 57: 940-946 https://doi.org/10.1038/sj.ejcn.1601628
  38. Peluso MR, Winters TA, Shanahan MF, Banz WJ. 2000. A cooperative interaction between soy protein and its isoflavone-enriched fraction lowers hepatic lipids in male obese Zucker rats and reduces blood platelet sensitivity in male Sprague-Dawley rats. J Nutr 130: 2333-2342
  39. Briviba K, Sies H. 1994. Natural antioxidnats in human health and disease. Frei B, ed. Academic press, San Diego, CA, USA. p 107-128
  40. Kameoka S, Leavitt P, Chang C. 1999. Expression of antioxidant properties in human intestinal Caco-2 cells treated with dietary isoflavonoids. Cancer Letters 146: 161-167 https://doi.org/10.1016/S0304-3835(99)00253-0
  41. Yamakoshi J, Piskula MK, Izumi T, Tobe K, Saito M, Kataoka S, Obata A, Kikuchi M. 2000. Isoflavone aglycon-rich extract without soy protein attenuates atherosclerosis development in cholesterol fed rabbits. J Nutr 130: 1887-1893
  42. Jeong MJ, Bang MH, Seol SM, Kim WK. 2002. The effects of isoflavone on lipid metabolism and immune responses in SD rats. Korean J Nutr 35: 635-642
  43. Cho SY, Oh YJ, Park JY, Lee MK, Kim MJ. 2003. Effect of dandelion (Taraxacum officinale) leaf extracts on hepatic antioxidative system in rats fed high cholesterol diet. J Korean Soc Food Sci Nutr 32: 458-463 https://doi.org/10.3746/jkfn.2003.32.3.458
  44. Connye K, Barbara CP. 1991. Changes in colonic antioxidant status in rats during long-term feeding of different high fat diet. J Nutr 121: 1562-1569 https://doi.org/10.1093/jn/121.10.1562
  45. Kang YH, Park YK, Ha TY, Moon KD. 1996. Effects of pine needle extracts on enzyme activities of serum and liver and liver morphology in rats fed high diet. J Korean Soc Food Sci Nutr 25: 374-378
  46. Frintche K, Johnston PV. 1988. Rapid autooxidation of fish oil in diets without added antioxidants. J Nutr 118: 425-426 https://doi.org/10.1093/jn/118.4.425
  47. Geeta S, Ravindra N, Kiran DG. 1991. Effect of ethanol on Cd-induced lipid peroxidation and antioxidant enzymes in rat liver. Biochem Pharmacol 42: S9-S16 https://doi.org/10.1016/0006-2952(91)90386-J

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