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Cholesterol Improvement Effects of Co-treatment with Black Raspberry and Red Ginseng Extracts in Mice Fed a High Cholesterol Diet

고콜레스테롤 식이 투여 마우스에서 복분자 미숙과 추출물과 홍삼농축액 복합 투여의 콜레스테롤 개선 효과

  • Received : 2014.06.13
  • Accepted : 2014.08.05
  • Published : 2014.10.31

Abstract

We examined the effects of unripe black raspberry (UBR) and red ginseng (RG) extracts on cholesterol improvement in C57BL/6J mice fed a HCD (high cholesterol diet) for 12 weeks. Hepatic total lipid and total cholesterol contents were significantly induced in hyperlipidemic mice. However, supplementation with UBR, RG and simvastatin effectively reduced these lipid profiles. Further, UBR and co-treatment with UBR and RG increased expression of LDL receptor, SREBP2, and SR-B1 mRNA compared with HCD. The ApoB/ApoA1 ratio was reduced by co-treatment with UBR and RG compared to treatment with UBR. In addition, histopathologic evaluation showed that co-treatment with UBR and RG suppressed lipid accumulation as well as FAS and leptin expression in plasma. These results indicate that co-treatment with UBR and RG may be useful for the prevention of hypercholesterolemia.

본 연구는 복분자 미숙과 물 추출물과 홍삼농축액으로 C57BL/6J 수컷 마우스를 이용하여 콜레스테롤 억제 효과 및 지질대사에 미치는 영향을 살펴보고, 기능성 식품으로의 가능성을 알아보았다. 실험동물은 C57BL/6J 수컷 마우스를 사용하였으며, 12주 동안 고콜레스테롤 식이를 급여하면서 복분자 미숙과 물 추출물과 홍삼농축액을 경구투여 하였다. 그 결과로 고콜레스테롤 식이군과 비교하였을 때 복분자 미숙과 추출물과 홍삼농축액 식이군에서 체중증가량, 식이 섭취량에는 변화가 없었다. 콜레스테롤 합성의 가장 중요한 기작인 LDL receptor와 SREBP2 발현에서는 복분자 미숙과 추출물 투여군과 복분자와 홍삼 복합 투여군 모두 유의적으로 증가하여 세포 안으로의 LDL 흡수를 촉진시킴으로써 체내 콜레스테롤을 낮추는 것으로 판단된다. HDL 관련 유전자 발현에서도 복분자 미숙과 추출물 투여군과 복분자와 홍삼 복합 투여군에서 HDL uptake 유전자인 SR-B1의 발현을 증가시켜 콜레스테롤 개선 효과를 보였다. 또한 간의 형태학적 변화에서는 고콜레스테롤 식이군과 비교하였을 때 복분자 미숙과 물 추출물과 홍삼농축액 복합 투여군에서 지방 형성이 현저히 줄어들었고, leptin과 FAS의 농도를 측정한 결과 유의적으로 감소하였다. 결과적으로 복분자 미숙과 물 추출물과 홍삼농축액 복합 투여가 콜레스테롤과 고지혈증 예방에 긍정적인 효과를 보일 것으로 사료된다.

Keywords

References

  1. Lim S, Shin H, Song JH, Kwak SH, Kang SM, Yoon JW, Choi SH, Cho SI, Park KS, Lee HK, Jang HC, Koh KK. 2011. Increasing prevalence of metabolic syndrome in Korea. Diabetes Care 34: 1323-1328. https://doi.org/10.2337/dc10-2109
  2. MHWK. 2003. Yearbook of Health and Welfare Statistics. Report of the Ministry of Health and Welfare, Seoul, Korea. p 35.
  3. Moon SJ. 1996. Nutritional problems of Korean. Korean J Nutr 29: 371-380.
  4. Mckenny JM. 2001. Lipid management: tools for getting to the goal. Am J Manag Care 7: S299-S306.
  5. Miettinen TA. 2001. Cholesterol absorption inhibition: a strategy for cholesterol-lowering therapy. Int J Clin Pract 55: 710-716.
  6. Shin MK, Han SH. 2002. Effects of methanol extracts from bamboo (Pseudosasa japonica Makino) leaves extracts on lipid metabolism in rats fed high fat and high cholesterol diet. Korean J Dietary Culture 17: 30-36.
  7. Eu GS, Chun BY, Bandopadhyay R, Yoo NH, Choi DG, Yun SJ. 2008. Phylogenic relationships of Rubus species revealed by randomly amplified polymorphic DNA markers. J Crop Sci Biotech 11: 39-44.
  8. Seeram NP, Adams LS, Zhang Y, Lee R, Sand D, Scheuller HS, Heber D. 2006. Blackberry, black raspberry, blueberry, cranberry, red raspberry and strawberry extracts inhibit growth and stimulated apoptosis of human cancer cells in vitro. J Agric Food Chem 54: 9329-9339. https://doi.org/10.1021/jf061750g
  9. Chen T, Hwang HJ, Rose ME, Nines RG, Stoner GD. 2006. Chemopreventive properties of black raspberries in N-nitrosomethylbenzylamine- induced rat esophageal tumorigenesis: down regulation of cyclooxygenase-2, inducible nitric oxide synthase and c-jun. Cancer Res 66: 2853-2859. https://doi.org/10.1158/0008-5472.CAN-05-3279
  10. Wang SY, Jiao H. 2000. Scavenging capacity of berry crops on superoxide radicals, hydrogen peroxide, hydroxyl radicals and singlet oxygen. J Agric Food Chem 48: 5677-5684. https://doi.org/10.1021/jf000766i
  11. Lee SJ, Lee MJ, Ko YJ, Choi HR, Jeong JT, Choi KM, Cha JD, Hwang SM, Jung HK, Park JH, Lee TB. 2013. Effects of extracts of unripe black raspberry and red ginseng on cholesterol synthesis. Korean J Food Sci Technol 45: 628-635. https://doi.org/10.9721/KJFST.2013.45.5.628
  12. Choi HR, Lee SJ, Lee JH, Kwon JW, Lee HK, Jeong JT, Lee TB. 2013. Cholesterol lowering effects of unripe black raspberry water extract. J Korean Soc Food Sci Nutr 42: 1899-1907. https://doi.org/10.3746/jkfn.2013.42.12.1899
  13. Yang HM, Oh SM, Lim SS, Shin HK, Oh YS, Kim JK. 2011. Antiinflammatory activities of Rubus coreanus depend on the degree of fruit ripening. Phytother Res 22: 102-107.
  14. Lee SH, Park JH, Cho NS, Yu HJ, You SK, Cho CW, Kim DC, Kim YH, Kim KH. 2009. Sensory evaluation and bioavailability of red ginseng extract (Rg1, Rb1) by complexation with $\gamma$-cyclodextrin. Korean J Food Sci Technol 41: 106-110.
  15. Yokozawa T, Kobayashi T, Oura H, Kawashima Y. 1985. Studies on the mechanism of the hypoglycemic activity of ginsenoside-Rb2 in streptozotocin-diabetic rats. Chem Pharm Bull (Tokyo) 33: 869-872. https://doi.org/10.1248/cpb.33.869
  16. Joo CN, Koo JH. 1980. Biochemical study of some parmacological effects of Panax ginseng C. A. Meyer. Korean Biochem J 13: 63-80.
  17. Yoon SH, Joo CN. 1993. Study on the preventive effect of ginsenosides against hypercholesterolemia and its mechanism. Korean J Ginseng Sci 17: 1-12.
  18. Kang BH, Koo JH, Joo CN. 1986. Effect of saponin fraction of Panax ginseng C. A. Meyer on blood serum lipoprotein distribution of cholesterol fed rabbits. Korean J Ginseng Sci 10: 114-121.
  19. Molcanyiova A, Stancakova A, Javorsky M, Tkac I. 2006. Beneficial effect of Simvastatin treatment on LDL oxidation and antioxidant protection is more pronounced in combined hyperlipidemia than in hypercholesterolemia. Pharmacol Res 54: 203-207. https://doi.org/10.1016/j.phrs.2006.04.009
  20. Song G, Liu J, Zhao Z, Yu Y, Tian H, Yao S, Li G, Qin S. 2011. Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat diet. Lipids Health Dis 10: 8. https://doi.org/10.1186/1476-511X-10-8
  21. Zhang X, Mao S, Luo G, Wei J, Berggren-Soderlund M, Nilsson-Ehle P, Xu N. 2011. Effects of Simvastatin on apolipoprotein M in vivo and in vitro. Lipids Health Dis 10: 112. https://doi.org/10.1186/1476-511X-10-112
  22. Lei YF, Chen JL, Wei H, Xiong CM, Zhang YH, Ruan JL. 2011. Hypolipidemic and anti-inflammatory properties of Abacopterin A from Abacopteris penangiana in high-fat diet-induced hyperlipidemia mice. Food Chem Toxicol 49: 3206-3210. https://doi.org/10.1016/j.fct.2011.08.027
  23. Neuschwander-Tetri BA, Clark JM, Bass NM, Van Natta ML, Unalp-Arida A, Tonascia J, Zein CO, Brunt EM, Kleiner DE, McCullough AJ, Sanyal AJ, Diehl AM, Lavine JE, Chalasani N, Kowdley KV. 2010. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 52: 913-924.
  24. Pal S, Ho N, Santos C, Dubois P, Mamo J, Croft K, Allister E. 2003. Red wine polyphenolics increase LDL receptor expression and activity and suppress the secretion of ApoB100 from human HepG2 cells. J Nutr 133: 700-706.
  25. Vinson JA, Teufel K, Wu N. 2001. Red wine, dealcoholized red wine, and especially grape juice, inhibit atherosclerosis in hamster model. Atherosclerosis 156: 67-72. https://doi.org/10.1016/S0021-9150(00)00625-0
  26. Suzuki T, Kumazoe M, Kim Y, Yamashita S, Nakahara K, Tsukamoto S, Sasaki M, Hagihara T, Tsurudome Y, Huang Y, Maeda-Yamamoto M, Shinoda Y, Yamaguchi W, Yamada K, Tachibana H. 2013. Green tea extract containing a highly absorbent catechin prevents diet-induced lipid metabolism disorder. Sci Rep 3: 2749. https://doi.org/10.1038/srep02749
  27. Mahley RW, Innerarity TL, Rall SC Jr, Weisgrader KH. 1984. Plasma lipoproteins: apoprotein structure and function. J Lipid Res 25: 1277-1294.
  28. Kim EJ, Lee HI, Chung KY, Noh YH, Ro YT, Koo JH. 2009. The ginsenoside-Rb2 lowers cholesterol and triacylglycerol levels in 3T3-L1 adipocytes cultured under high cholesterol or fatty acids conditions. BMB Rep 42: 194-199. https://doi.org/10.5483/BMBRep.2009.42.4.194
  29. Lee S, Lee MS, Kim CT, Kim IH, Kim Y. 2012. Ginsenoside Rg3 reduces lipid accumulation with AMP-activated protein kinase (AMPK) activation in HepG2 cells. Int J Mol Sci 13: 5729-5739. https://doi.org/10.3390/ijms13055729
  30. Bursill CA, Abbey M, Roach PD. 2007. A green tea extract lowers plasma cholesterol by inhibiting cholesterol synthesis and upregulating the LDL receptor in the cholesterol-fed rabbit. Atherosclerosis 193: 86-93. https://doi.org/10.1016/j.atherosclerosis.2006.08.033
  31. Magana MM, Koo SH, Towle HC, Osborne TF. 2000. Different sterol regulatory element-binding protein-1 isoforms utilize distinct co-regulatory factors to activate the promoter for fatty acid synthase. J Biol Chem 275: 4726-4733. https://doi.org/10.1074/jbc.275.7.4726
  32. Shimano H. 2001. Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog Lipid Res 40: 439-452. https://doi.org/10.1016/S0163-7827(01)00010-8
  33. Tsujita M, Wu CA, Abe-Dohmae S, Usui S, Okazaki M, Yokoyama S. 2005. On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway. J Lipid Res 46: 154-162. https://doi.org/10.1194/jlr.M400402-JLR200
  34. Brundert M, Heeren J, Bahar-Bayansar M, Ewert A, Moore KJ, Rinninger F. 2006. Selective uptake of HDL cholesteryl esters and cholesterol efflux from mouse peritoneal macrophages independent of SR-BI. J Lipid Res 47: 2408-2421. https://doi.org/10.1194/jlr.M600136-JLR200
  35. Krause BR, Auerbach BJ. 2001. Reverse cholesterol transport and future pharmacological approaches to the treatment of atherosclerosis. Curr Opin Investig Drugs 2: 375-381.
  36. Uto-Kondo H, Ayaori M, Ogura M, Nakaya K, Ito M, Suzuki A, Takiguchi S, Yakushiji E, Terao Y, Ozasa H, Hisada T, Sasaki M, Ohsuzu F, Ikewaki K. 2010. Coffee consumption enhances high-density lipoprotein-mediated cholesterol efflux in macrophages. Circ Res 106: 779-787. https://doi.org/10.1161/CIRCRESAHA.109.206615
  37. Berrougui H, Grenier G, Loued S, Drouin G, Khalil A. 2009. A new insight into resveratrol as an atheroprotective compound: inhibition of lipid peroxidation and enhancement of cholesterol efflux. Atherosclerosis 207: 420-427. https://doi.org/10.1016/j.atherosclerosis.2009.05.017
  38. Wang X, Mu H, Chai H, Liao D, Yao Q, Chen C. 2007. Human immunodeficiency virus protease inhibitor ritonavir inhibits cholesterol efflux from human macrophage-derived foam cells. Am J Pathol 171: 304-314. https://doi.org/10.2353/ajpath.2007.060965
  39. Walldius G, Jungner I. 2006. The apoB/apoA1 ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy - a review of the evidence. J Intern Med 259: 493-519. https://doi.org/10.1111/j.1365-2796.2006.01643.x
  40. Behme MT. 1996. Leptin: product of the obese gene. Nutr Today 31: 138-141. https://doi.org/10.1097/00017285-199607000-00002
  41. Lee YJ, Kim HY, Yoon JJ, Lee SM, Ahn YM, Kho JH, Kho MC, Lee HS, Cho KM, Kang DG. 2012. Beneficial effect of combination with Korean red ginseng and Morus alba in metabolic syndrome. Kor J Herbology 27: 99-105. https://doi.org/10.6116/kjh.2012.27.6.99
  42. Hsu CL, Yen GC. 2007. Effect of gallic acid on high fat diet-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats. Br J Nutr 98: 727-735.
  43. Wu Y, Yu Y, Szabo A, Han M, Huang XF. 2014. Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet. PLoS One 9: e92618. https://doi.org/10.1371/journal.pone.0092618
  44. Wang X, Song KS, Guo QX, Tian W. 2003. The galloyl moiety of green tea catechins is the critical structural feature to inhibit fatty-acid synthase. Biochem Pharmacol 66: 2039-2047. https://doi.org/10.1016/S0006-2952(03)00585-9
  45. Yasui K, Paeng N, Miyoshi N, Suzuki T, Taguchi K, Ishigami Y, Fukutomi R, Imai S, Isemura M, Nakayama T. 2012. Effects of a catechin-free fraction derived from green tea on gene expression of enzymes related to lipid metabolism in the mouse liver. Biomed Res 33: 9-13. https://doi.org/10.2220/biomedres.33.9

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