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Reduction of Plasma Triglycerides and Cholesterol in High Fat Diet-Induced Hyper-Lipidemic Mice by n-3 Fatty Acid from Bokbunja (Rubus coreanus Miquel) Seed Oil

오메가-3 지방산 함유 복분자종자유에 의한 고지방식이 유도 고지혈증 마우스의 혈중 중성지방 및 콜레스테롤 감소 효과

  • Received : 2015.03.25
  • Accepted : 2015.04.10
  • Published : 2015.07.31

Abstract

To investigate the effect of n-3 fatty acid from Bokbunja (Rubus coreanus Miq.) seed oil (BSO), we examined improvement of plasma triglycerides and cholesterol in vivo. Five-week-old ICR mice were divided into five groups of six mice each; Control, high fat diet (HFD) control (negative control), salmon oil control (positive control, HFD+commercial n-3 fatty acid), and BSO experimental groups (HFD+1 g/60 kg BW/d, HFD+2 g/60 kg BW/d). After 4 weeks of BSO treatment, we measured serum triglyceride and cholesterol levels. The levels of low-density lipoprotein/very-low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and total cholesterol were significantly (P<0.05) reduced in the group fed BSO at 2 g/60 kg BW/d compared to the negative control. Levels of triglycerides, which are similar to cholesterol, were also significantly (P<0.05) reduced in the same group. To investigate further, we tested blood coagulation parameters. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were not significantly different among the five groups according to BSO. However, the 2 g/60 kg BW/d BSO group treated with PT and aPTT showed a tendency to live longer than the negative control. Taken together, BSO might improve blood homeostasis mediated via hypo-lipidemic and anti-coagulation activities.

본 실험의 복분자종자유는 리놀렌산 238.3 mg/g, 리놀레산과 감마리놀렌산 427.1 mg/g을 포함하며 이는 고시된 범위내의 섭취량이므로 독성시험 없이 4주 동안 매일 경구 투여로 암컷과 수컷 쥐 모두에게 섭취하도록 하였다. 또한 성인 정상체중을 약 60 kg으로 설정하고 60 kg의 성인이 하루 1 g, 2 g을 각각 섭취할 때의 혈중 지방의 감소 효과를 알아보기 위해 급이군의 설정을 1 g/60 kg BW/d(BSO 1 g), 2 g/60 kg BW/d(BSO 2 g)로 정하였다. 양성대조군의 경우에 판매되는 연어유 1,000 mg 캡슐을 2정 섭취하는 것을 권장하였고, 이에 맞추어 2 g/60 kg BW/d로 설정하게 되었다. 실험기간 종료 후 마우스를 희생시켜 혈액을 얻었으며, 복분자종자유(BSO 2 g)를 섭취한 마우스에서 총콜레스테롤 및 HDL, LDL/VLDL-콜레스테롤과 혈중 중성지방이 유의적으로 감소하는 것을 확인할 수 있었다(P<0.05). 이를 종합해 보았을 때 복분자종자유는 고지혈증 상태를 개선하고 미약하지만 항응고 활성을 통해 혈액의 항상성을 유지하도록 돕는 작용을 한다고 할 수 있다. 따라서 앞으로 동물 유래가 아닌 식물유래 복분자종자유를 이용한다면 고지혈증 개선 효과와 혈액 항응고 활성을 조절할 수 있을 것이며, 더욱 다양한 표적 인자 분석을 통하여 복분자종자유의 고지혈, 항응고 및 혈행개선 기전연구가 가능할 것이라 판단된다.

Keywords

References

  1. Cho SH. 1994. Dietary lipid and atherosclerosis. J Korean Soc Food Nutr 23: 170-179.
  2. Lee YS, Lee MY, Lee SY. 2014. The risk of metabolic syndrome by dietary patterns of middle-aged adults in Gyeonggi province. Korean J Community Nutr 19: 527-536. https://doi.org/10.5720/kjcn.2014.19.6.527
  3. Park YS, Park HJ, Won SI. 2011. Association of fatty acid intake and dyslipidemia in Korean adults: Korea national health and nutrition survey, 1998-2007. J East Asian Soc Dietary Life 21: 789-807.
  4. Statistics Korea. 2014. 2013 cause of death statistics. Statistics Korea, Daejeon, Korea. p 4-43.
  5. Hong SJ, Oh DJ, Kim EJ, Lee SJ, Shin SH, Choi JI, Choi CW, Park JS, Ahn JC, Park CG, Seo HS, Ro YM. 2003. The comparison of serum lipid levels and risk factors according to the status of coronary atherosclerosis in Koreans. Korean Circ J 33: 465-474. https://doi.org/10.4070/kcj.2003.33.6.465
  6. Hwang WM, Bae JH, Kim KY, Synn YC. 2005. Impacts of atherosclerotic coronary risk factors on atherosclerotic surrogates in patients with coronary artery disease. Korean Circ J 35: 131-139. https://doi.org/10.4070/kcj.2005.35.2.131
  7. Chung HK, Shin MJ, Cha YJ, Lee KH. 2011. Effect of onion peel extracts on blood lipid profile and blood coagulation in high fat fed SD rats. Korean J Food & Nutr 24: 442-450. https://doi.org/10.9799/ksfan.2011.24.3.442
  8. Cheon JH, Lee JY, Kim JH, Park MH, Lee SH, Kong CS, Kim YY, Yu KH, Kim MH. 2015. Effects of fermented Saragassum thunbergii on platelet aggregation and serum lipid levels in obese rat induced by high fat diet. Journal of Life Science 25: 456-462. https://doi.org/10.5352/JLS.2015.25.4.456
  9. Lim HJ, Cho KH, Choue R. 2005. The effects of functional tea (Mori Folium, Lycii Fructus, Chrysanthemi Flos, Zizyphi Fructus, Sesamum Semen, Raphani Semen) supplement with medical nutrition therapy on the blood lipid levels and antioxidant status in subjects with hyperlipidemia. J Korean Soc Food Sci Nutr 34: 42-56. https://doi.org/10.3746/jkfn.2005.34.1.042
  10. Lee MJ, Lee SJ, Choi HR, Lee JH, Jeong JT, Choi KM, Cha JD, Hwang SM, Park JH, Lee JH, Lee TB. 2014. Cholesterol improvement effects of co-treatment with black raspberry and red ginseng extracts in mice fed a high cholesterol diet. J Korean Soc Food Sci Nutr 43: 1491-1499. https://doi.org/10.3746/jkfn.2014.43.10.1491
  11. Sanders TAB, Lewis F, Slaughter S, Griffin BA, Griffin M, Davies I, Millward DJ, Cooper JA, Miller GJ. 2006. Effect of varying the ratio of n-6 to n-3 fatty acids by increasing the dietary intake of $\alpha$-linolenic acid, eicosapentaenoic and docosahexaenoic acid, or both on fibrinogen and clotting factors VII and XII in persons aged 45-70 y: the OPTILIP study. Am J Clin Nutr 84: 513-522.
  12. Lee SN, Park HK, Kim YE, Hwang IH, Huh BY. 1991. Lipid-lowering effect of omega-3 fatty acid in patients with hypercholesterolemia. J Korean Acad Fam Med 12: 1-7.
  13. Laidlaw M, Holub BJ. 2003. Effects of supplementation with fish oil-derived n-3 fatty acids and ${\gamma}$-linolenic acid on circulating plasma lipids and fatty acid profiles in women. Am J Clin Nutr 77: 37-42.
  14. Robinson JG, Stone NJ. 2006. Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids. Am J Cardiol 98: 39-49.
  15. Lovegrove JA, Lovegrove SS, Lesauvage SV, Brady LM, Saini N, Minihane AM, Williams CM. 2004. Moderate fishoil supplementation reverses low-platelet, long-chain n-3 polyunsaturated fatty acid status and reduces plasma triacylglycerol concentrations in British Indo-Asians. Am J Clin Nutr 79: 974-982.
  16. Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP, Gallagher PJ, Calder PC, Grimble RF. 2003. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 361: 477-485. https://doi.org/10.1016/S0140-6736(03)12468-3
  17. Djoussé L, Arnett DK, Carr JJ, Eckfeldt JH, Hopkins PN, Province MA, Ellison RC. 2005. Dietary linolenic acid is inversely associated with calcified atherosclerotic plaque in the coronary arteries: the National Heart, Lung, and Blood Institute Family Heart Study. Circulation 111: 2921-2926. https://doi.org/10.1161/CIRCULATIONAHA.104.489534
  18. Lopez-Garcia E, Schulze MB, Manson JE, Meigs JB, Albert CM, Rifai N, Willett WC, Hu FB. 2004. Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women. J Nutr 134: 1806-1811.
  19. Ambring A, Johansson M, Axelsen M, Gan L, Strandvik B, Friberg P. 2006. Mediterranean-inspired diet lowers the ratio of serum phospholipid n-6 to n-3 fatty acids, the number of leukocytes and platelets, and vascular endothelial growth factor in healthy subjects. Am J Clin Nutr 83: 575-581.
  20. Jeong S, Kim JY, Paek JE, Kim J, Kwak JS, Kwon O. 2013. Systematic review of the effect of omega-3 fatty acids on improvement of blood flow while focused on evaluation of claims for health functional food. J Nutr Health 46: 226-238. https://doi.org/10.4163/jnh.2013.46.3.226
  21. Jeon YH, Choi SW, Kim MR. 2009. Antimutagenic and cytotoxic activity of ethanol and water extracts from Rubus coreanum. Korean J Food Cookery Sci 25: 379-386.
  22. Kim MJ, Lee U, Kim SH, Chung HG. 2002. Variation of leaf, fruiting characteristics in Rubus coreanus Miq. Korean J Breed 34: 50-56.
  23. Cha HS, Youn AR, Park PJ. Choi HR, Kim BS. 2007. Comparison of physiological acvivities of Rubus coreanus and Miquel during maturation. J Korean Soc Food Sci Nutr 36: 683-688. https://doi.org/10.3746/jkfn.2007.36.6.683
  24. Lee MJ, Lee SJ, Choi HR, Lee JH, Kwon JW, Chae KS, Jeong JT, Lee TB. 2014. Improvement of cholesterol and blood pressure in fruit, leaf and stem extracts from black raspberry in vitro. Korean J Medicinal Crop Sci 22: 177-187. https://doi.org/10.7783/KJMCS.2014.22.3.177
  25. Ohtani K, Miyajima C, Takahasi T, Kasai R, Tanaka O, Hahn DR, Naruhashi N. 1990. A dimeric triterpene-glycoside from Rubus coreanus. Phytochemistry 29: 3275-3280. https://doi.org/10.1016/0031-9422(90)80199-Q
  26. Kim YH, Kang SS. 1993. Triterpenoids from Rubus Fructus (Bogbunja). Arch Pharm Res 16: 109-113. https://doi.org/10.1007/BF03036856
  27. Choi MR, Lee MY, Kim JE, Hong JE, Jang K, Lee JY, Chun JW, Kim TH, Shin HK, Kim EJ. 2012. Rubus coreanus Miquel improves on impairment of memory in senescenceaccelerated mouse (SAM). J Korean Soc Food Sci Nutr 41: 1253-1258. https://doi.org/10.3746/jkfn.2012.41.9.1253
  28. Choung MG, Lim JD. 2012. Antioxidant, anticancer and immune activation of anthocyanin fraction from Rubus coreanus Miquel fruits (Bokbunja). Korean J Medicinal Crop Sci 20: 259-269. https://doi.org/10.7783/KJMCS.2012.20.4.259
  29. Jeong HS, Han JG, Ha JH, Kim Y, Oh SH, Kim SS, Jeong MH, Choi GP, Park UY, Lee HY. 2009. Antioxidant activities and skin-whitening effects of nano-encapsuled water extract from Rubus coreanus Miquel. Korean J Medicinal Crop Sci 17: 83-89.
  30. Choe M, Shin GJ, Choi GP, Do JH, Kim JD. 2003. Synergistic effects of extracts from Korean red ginseng, Saururus chinensis (Lour.) Baill. and Rubus coreanus Miq. on antioxidative activities in rats. Korean J Medicinal Crop Sci 11: 148-154.
  31. Won KS, Lee TW, Eun JS, Song JM. 2003. Effect of Rubus coreanus Miquel on the specific immune response in mice. Korean J Oriental Physiology & Pathology 17: 656-661.
  32. Kwon MC, Kim CH, Na CS, Kwak HG, Kim JC, Lee HY. 2007. Comparison of immuno-modulatory regulatory activities of Rubus coreanus Miquel by ultra high pressure extracts process. Korean J Medicinal Crop Sci 15: 398-404.
  33. Shin H, Lee H. 2010. Effects of pharmacopuncture with RUBI FRUCTUS infusion solution at KI10 on osteoporotic rats induced by ovariectomy. The Journal of Korean Acupuncture & Moxibustion Society 27: 99-114.
  34. Karvonen HM, Aro A, Tapola NS, Salminen I, Uusitupa MI, Sarkkinen ES. 2002. Effect of $\alpha$-linolenic acid-rich Camelina sativa oil on serum fatty acid composition and serum lipids in hypercholesterolemic subjects. Metabolism 51: 1253-1260. https://doi.org/10.1053/meta.2002.35183
  35. Zatonski W, Campos H, Willett W. 2008. Rapid declines in coronary heart disease mortality in Eastern Europe are associated with increased consumption of oils rich in alpha- linolenic acid. Eur J Epidemiol 23: 3-10. https://doi.org/10.1007/s10654-007-9195-1
  36. Ayerza R, Coates W. 2005. Ground chia seed and chia oil effects on plasma lipids and fatty acids in the rat. Nutrition Research 25: 995-1003. https://doi.org/10.1016/j.nutres.2005.09.013
  37. Bae JH, Kim KB, Kim KS, Han SW, Kim YN, Park SY, Lee IK, Kim KY, Nam CW, Huh IS, Lee HJ, Lee SM. 1998. The effect of vitamin E on the endothelial function following a single high-fat meal in normal subjects, patients with coronary heart disease and patients with diabetes. Korean Circulation J 28: 1538-1551. https://doi.org/10.4070/kcj.1998.28.9.1538
  38. Lim JY, Kim OH, Kim JH. 2006. Effects of antioxidant supplementation on lipid profiles in elderly women. Korean J Community Nutr 11: 133-142.
  39. Lee CM. 2000. The effect of the administration of red ginseng and vitamin E on the activation of antioxidizing enzyme and the formation of lipid peroxidation in blood. The Korean Journal of Physical Education 39: 476-488.
  40. Jo HJ, Kim JW, Yoon JA, Kim KI, Chung KH, Song BC, An JH. 2014. Antioxidant activities of Amarnth (Amaranthus spp. L.) flower extracts. Korean J Food & Nutr 27: 175-182. https://doi.org/10.9799/ksfan.2014.27.2.175
  41. Chung SH, Moon YJ, Kim SG, Kim KY, Lee KT, Kim HK, Whang WK. 2008. Isolation of flavonoids from Carthami flos and their antioxidative activity. Yakhak Hoeji 52: 241-251.
  42. Park S, Chae KS, Son RH, Jung J, Im Y, Kwon JW. 2012. Quality characteristics and antioxidant activity of bokbunja (black raspberry) vinegars. Food Eng Prog 16: 340-346.
  43. Lee JW, Do JH. 2000. Determination of total phenolic compounds from the fruit of Rubus coreanum and antioxidative activity. J Korean Soc Food Sci Nutr 29: 943-947.
  44. Choi Y, Lee YJ, Lee S, Chae C, Park S, Kim SS, An H, King D, Han C, Hong H. 2012. Effect of concentrated Dangyooja-derived flavonoids extract added to citrus beverage on obesity and blood lipids in rats. Kor J Hort Sci Technol 30: 214-219.
  45. Lee SJ, Park HJ, Song Y, Jang SH, Goo AJ, Ko YG, Cho JH. 2014. Antioxidant activity and anti-obesity effect of Coprinus comatus in Zucker rat (fa/fa). Korean J Ver Serv 3: 51-58.
  46. Terpstra AH, Beynen AC, Everts H, Kocsis S, Katan MB, Zock PL. 2002. The decrease in body fat in mice fed conjugated linoleic acid is due to increases in energy expenditure and energy loss in the excreta. J Nutr 132: 940-945.
  47. Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O. 2005. Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans. J Nutr 135: 778-784.

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