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The Effects of Seaweed Gongjindan on Estrogen like Activities, Platelet Aggregation and Serum Lipid Levels in Ovariectomized Rats

해조공진단의 에스트로겐 유사활성 및 난소를 절제한 흰쥐의 혈소판 응집과 혈청 내 지질 조성에 미치는 영향

  • Jeon, Myeongjeong (Department Food and Nutrition, Silla University) ;
  • Kim, Seoyeon (Department Food and Nutrition, Silla University) ;
  • Kim, Bo-Kyung (Department Food and Nutrition, Silla University) ;
  • Cheon, Jihyeon (Department Food and Nutrition, Silla University) ;
  • Park, Seong-Hwan (Department of Pharmaceutical Engineering, Silla University) ;
  • Oh, Eunjin (Korea Traditional Food & Medicine, Pukyeong National University) ;
  • Lee, Sang-Hyeon (Department of Pharmaceutical Engineering, Silla University) ;
  • Kim, Mihyang (Department Food and Nutrition, Silla University)
  • Received : 2013.08.20
  • Accepted : 2013.09.26
  • Published : 2013.09.30

Abstract

Estrogen like activities were evaluated using ethanol and hot water extracts of gongjindan (GJD) and 3 types of brown algae by an in vitro detection system. Laminaria japonica and Undaria pinnatifida represented statistically significant (p<0.001) estrogen like activities, while GJD and Ecklonia stolonifera did not. Furthermore, activities of hot water extracts ($500{\mu}g/ml$) of Laminaria japonica and three mixture (Ecklonia stolonifera : Undaria pinnatifida : Laminaria japonica, 1: 1: 1) were stronger than that of $10^{-7}M$ $17{\beta}$-estradiol. These results suggest that Laminaria japonica contain estrogen like compounds. Based on these results, the prepared seaweed GJD were used for animal experiments about the effects on inhibition of platelet aggregation and serum lipid levels in ovariectomized rats. 9-week Old female SD-rats were randomly assigned to 3 groups as sham-operated rats, ovariectomized rats and ovariectomized rats that were treated with GJD. The rats were placed on prescribed diets for 5 weeks following ovariectomy. Total cholesterol and triglyceride contents on serum decreased in the SHAM group compared to the OVX-CON group. 5 weeks feeding of GJD resulted in significant lowering of triglyceride and a decreasing tendency of total cholesterol level. The level of HDL-cholesterol on serum increased significantly by feeding diets containing the GJD. The ability of platelet aggregation of group treated with GJD was less than that of the OVX-CON group. These results suggest that the beneficial effects of seaweed gongjindan may be used to improve menopausal syndrome.

갱년기의 여성에는 여러 폐경 증후들이 나타나는데, 특히 에스트로겐의 감소로 인한 혈중의 지질 조성의 변화 등으로 골다공증 및 심혈관계 질환의 발병율이 높아지게 된다. Estrogen의 감소는 다양한 생리적 변화를 초래하며 특히 심혈관계 질환을 빠르게 진행시킨다고 보고되고 있다. 본 연구에서는 에스트로겐 유사활성이 뛰어난 갈조류를 선정하여 해조공진단을 제조하였으며, 실험동물인 흰쥐의 난소를 절제하여 인위적으로 갱년기를 유도한 후 해조공진단이 혈소판 응집능 및 혈중 지질 함량에 미치는 영향을 검토하였다. 에스트로겐 검출시스템을 사용하여 공진단 및 갈조류 추출물의 에스트로겐 유사활성을 검증한 결과, 다시마 및 곰피 열수 추출물에서는 통계적으로 유의한 에스트로겐 유사활성이 나타났으며, 특히 다시마 열수 추출물에서 가장 높은 활성이 나타났다. 이러한 in vitro 실험 결과를 통해 다시마 추출물을 첨가한 해조공진단을 제조한 후, 갱년기를 유도한 실험동물에 투여하여 혈소판 응집능 및 혈청 내 지질 조성에 미치는 영향을 검토하였다. 총 콜레스테롤 함량은 해조공진단 투여로 인해 OVX-CON군에 비해 감소하는 경향을 나타내었으나 유의적인 결과가 나타나지 않은 반면, 혈청 중 중성지방 함량의 경우, 해조공진단을 투여한 OVX-GJD군은 OVX-CON군과 비교하여 중성지방 함량이 유의적으로 감소하는 결과가 나타났다. 혈청 중 HDL-콜레스테롤 농도는 정상군인 SHAM군에 비해 난소를 절제한 OVX-CON군이 유의적으로 감소하였으나, 해조공진단을 첨가한 사료 섭취군(OVX-GJD)은 OVX-CON군에 비해 유의적으로 증가하는 결과를 나타내었다. 또한, 혈소판 응집 저해능을 검토한 결과에서 OVX-CON군에 비해 OVX-GJD군의 혈소판 응집이 유의적으로 감소하여 저해하는 경향을 나타내었다. 따라서 본 연구를 통해 제조된 해조공진단이 에스트로겐 유사활성을 가지고 있으며, 난소절제로 갱년기를 유도한 실험동물에게 이를 섭취시킨 결과 혈중 지질 개선 및 혈소판 응집 저해 효과가 나타나 갱년기 증상 완화에 활용 될 수 있는 소재로 기대된다.

Keywords

References

  1. Anderson, J. W., Johnstone, B. M. and Cook-newell, M. E. 1995. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 33, 276-282.
  2. Badimon, L., Badimon, J. J., Penny, W., Webster, M. W., Chesebro, J. H. and Fuster, V. 1992. Endothelium and atherosclerosis. J Hypertens 10, 43-50. https://doi.org/10.1097/00004872-199207001-00007
  3. Barrett-Connor, E. and Bush, T. L. 1991. Estrogen and coronary heart disease in women. JAMA 265, 1861-1867. https://doi.org/10.1001/jama.1991.03460140089033
  4. Belchetz, P. E. 1994. Hormonal treatment of postmenopausal women. N Engl J Med 14, 1062-1071.
  5. Bonithon-Kopp, C., Scarabin, P. Y., Darne, B., Malmejac, A. and Guize, L. 1990. Menopause-related changes in lipoproteins and some other cardiovascular risk factors. Int J Epidemiol 19, 42-48. https://doi.org/10.1093/ije/19.1.42
  6. Campagnoli1, C., Biglia, N., Peris, C. and Sismondi, P. 1995. Potential impact on breast cancer risk of circulating insulinlike growth factor I modifications induced by oral HRT in menopause. Gynecol Endocrinol 9, 67-74. https://doi.org/10.3109/09513599509160194
  7. Campos, H., Wilson Peter, W. F., Jimenez, D., Mcnanara, J. R., Ordovas, J. and Schaefer, E. J. 1990. Differences in apolipoproteins and low density lipoprotein subfractions in postmenopausal women on and off estrogen therapy: Results from the Framingham off spring study. Metabolism 39, 1033- 1038. https://doi.org/10.1016/0026-0495(90)90162-6
  8. Cha, S. H., Ahn, G. N., Heo, S. J., Kim, K. N., Lee, K. W., Song, B. S., Cho, S. K. and Jeon, Y. J. 2006. Screening of extracts from marine green and brown algae in Jeju for potential marine angiotensin-I converting enzyme (ACE) inhibitory activity. J Korean Soc Food Sci Nutr 35, 307-314. https://doi.org/10.3746/jkfn.2006.35.3.307
  9. Choi, G. H. 2007. (An) analysis of the Gongjindan;s ingredients and its efficacy on anti-oxidation. Ph D Dissertation. Daegu Haany University.
  10. Clarkson, T. B. 2002. Soy phytoestrogens a cardiovascular disease. J Nutr 132, 566-569.
  11. Furie, B. and Furie, B. C. 1988. The molecular basis of blood cogulation. Cell 53, 505-518. https://doi.org/10.1016/0092-8674(88)90567-3
  12. Gavey, D. A. 1986. The menopause and climacteric. In : Whitfield, C. R. ed. Dewhurst's text-book of obstetrics and gynecology for postgraduates. 4th eds., Oxford: Blackwell scientific publications, 646-676.
  13. Grodstein, F., Stampfer, M. S., Manson, J. E. 1996. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 335, 453-461. https://doi.org/10.1056/NEJM199608153350701
  14. Gale, S. K. and Sclakani, A. 1977. Comparison of ovarian and hypothalamic obesity syndromes in the female rat: effect of diet palatability on food intake and body weight. J Comp Physiol Psychol 91, 381-392. https://doi.org/10.1037/h0077328
  15. Hwang, S. M. 2004. The Effects of KongJin-Dan (KJD) on the Alzheimer's Disease Model Induced by CT105 and $\beta$-amyloid. MS Thesis. Daegu Haany University.
  16. Hur, H. 2008. Hepatoprotective Effects of GongJinDan, on Ethanol-mediated Experimental Liver Damage in Rats. Ph D Dissertation. Daegu Haany University.
  17. Im, E. Y. 2006. Protective Effects of Gongjindan on Adriamycin - Induced Apoptosis in H9c2 Cardionmyoblast Cells. Ph D Dissertation. Wonkwang University.
  18. Jang, H. K. and Cha, B. K. 2003. Influencing factors of climacteric women´s depression. J Korean Acad Nurs 33, 972-980.
  19. Jeon, M. H. 2011. Effect of Hijikia fusiforme fractions on proliferation and differentiation in osteoblastic MC3T3-E1 Cells. J Life Sci 21, 300-308. https://doi.org/10.5352/JLS.2011.21.2.300
  20. Je, S. Y. and Park, W. H. 1998. The Relationehip of Cardiopulmonary Fitness to Plasma Fibrinogen, Plasminogen Activator Inhibitor Type-1 (PAI-1), and Lipoprotein (a) [LP(a)] in Healthy Postmenopausal Women. J Korean Sports Med 16, 282-291.
  21. Kim, J. Y. and Kim, M. H. 2005, The Effects of Hijikia fusiforme on Serum Lipid Levels in Ovariectomized Rats. J Life Sci 15, 242-247. https://doi.org/10.5352/JLS.2005.15.2.242
  22. Kim, S. N. 2007. Effect of rose essential oil on female hormones in menopausal women. MS Thesis. Chung-Ang University.
  23. Kim, Y. K., Jeon, M. H., Park, Y. S., Hwang, H. J., Lee, S. H., Kim, S. G., Kim, Y. Y. and Kim, M. H. 2010. The Effect of Ecklonia stolonifera extracts on blood flow and serum lipid level in ovariectomozed rats. J Life Sci 20, 1851-1858. https://doi.org/10.5352/JLS.2010.20.12.1851
  24. Lee, H. S. 2001. Experiences of postmenopausal women about hormone replacement therapy. MS Thesis, Graduate School of Chungang University, Korea.
  25. Lee, I. K. and Gang, S. W. 1986. A check list of marine algae in Korea. Algae 2, 311-325.
  26. Lee, L. Y., Cheorun, J. and Byun, M. W. 2005. Application of irradiation technology for development of functional natural materials. Food Indus Nutr 10, 26-31.
  27. Lee, J. M. 2003. Effects of Yangyigongjindan on the Reproductive Competence of Aged Mice. Ph D Dissertation. Kyunghee University.
  28. Lee, S. S. and Park, J. H. 1989. Long-term effect of ovariectomy on body composition. Korean J Nutr 22, 102-107.
  29. Levine, G. N., Keaney, J. F. and Vita, J. A. 1995. Cholesterol reduction cardiovascular disease; Clinical benefits and possible mechanisms. N Engl J Med 33, 512-521.
  30. Lisa, K. 2009. Mechanisms of platelet activation: Need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost 2, 248-257.
  31. Manolio, T. A., Pearson, T. A., Wenger, N. K., Barrett-Connor, E., Opayne, G. H. and Harlan, W. R. 1992. Cholesterol and heart disease in older persons and women. Review of an NHLBI workshop. Ann Epidemiol 2, 161-176.
  32. Mook, D. G., Kenney, N. J., Roberts, S. and Nussbaum, A. I. 1972. Ovarian-adrenal interactions in regulation of body weight by female rats. J Comp Physiol Psychol 81, 192-211.
  33. Mueller, K. and Hsiao, S. 1980. Estrus and ovariectomy-induced body weight changes: evidenced for two estrogenic mechanisms. J Comp Physiol Psychol 5, 1126-1134.
  34. Park, Y. S. 2011. Effects of eisenia bicyclis extracts on lipids and bone turnover in ovariectomized rats. MS Thesis. Silla University.
  35. Park, Y. S. and Kim, M. H. 2012. The effect of eisenia bicyclis extracts on antioxidant activity and serum lipid level in ovariectomized rats. J Life Sci 22, 1407-1414. https://doi.org/10.5352/JLS.2012.22.10.1407
  36. Park, S. H., Jang, M. J., Hong, J. H., Rhee, S. J. and Choi, K. H. 2007. Effects of mulberry leaf extract feeding on lipid status of rats fed high cholesterol diets. J Korean Soc Food Sci Nutr 36, 3-50. https://doi.org/10.3746/jkfn.2007.36.1.043
  37. Ponglikitmongkol, M., White, J. H. and Chambon, P. 1990. Synergistic activation of transcription by the human estrogen receptor bound to tandem responsive elements. EMBO J 9, 2221-2231.
  38. Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Kooperberg, C., Stefanick, M. L., Jackson, R. D., Beresford, S. A., Howard, B. V., Johnson, K. C., Kotchen, J. M. and Ockene, J. 2002. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial. JAMA 288, 321-333. https://doi.org/10.1001/jama.288.3.321
  39. Stampfer, M. J. and Colditz, G. A. 1991. Estrogen replacement therapy and coronary heart disease : a quantitative assessment of the epidemiologic evidence. Prev Med 20, 47-63. https://doi.org/10.1016/0091-7435(91)90006-P
  40. Schemmel, R. A. and Teague, R. T. 1982. Obesity in Osborne mendel and S 4B/P1 rats: effects of sucrose solution, castration and treatment with estradiol or insulin. Am J Physiol 243, 347-352.
  41. Shimizu, H. and Shimomura, Y. 1992. Colonic temperature was not changed in the development of obesity after ovariectomy. Exp Clin Endocrinol 2, 99-101.
  42. Siess, W. 1989. Molecular mechanism of platelet activation. Physiol Rev 69, 58-178.
  43. Kim, O. S. 2004. Verification of estrogen-like activities in products of pomegranate extract using in vitro test system. College of Natural Sciences, Silla University. 13, 107-111.
  44. Yamazaki, I. and Yamaguchi, H. 1989. Characteristics of an ovariectomized osteogenic rat model. J Bone Miner Res 4, 13-22.
  45. Zeher, A. M., Schachlinger, V. and Hohnlosr, S. H. 1994. Coronary atherosclerotic wall thickening and vascular reactivity in humans: Elevated high-density lipoprotein levels ameliorate abnormal vasoconstriction in early atherosclerosis. Circulation 25, 2525-2532.