나린진이 고지방 및 고콜레스테롤 식이 랫드의 혈청 성분 농도의 변화에 미치는 영향

Effect of Naringin on Major Biochemical Parameters in Sera of Rats Fed High Fat and Cholesterol Diet

  • 황의경 (상지대학교 생명자원과학대학 동물자원학과)
  • Hwang, Eui-Kyung (Department of Animal Science, College of Life Science and Natural Resources, Sangji University)
  • 발행 : 2009.06.30

초록

This study was performed to investigate the changes of the serological lipid-related parameters of the rats when they were fed with the high fat diets supplemented with or without naringin for five weeks. Twenty-four Sprague-Dawley male rats($272.2{\pm}7.2$ g of body weight) were randomly divided into three groups(eight rats per each group) : control(C) group and two treatment groups. Rats in the C group were fed with the high-fat diet containing 15% lard, 1% cholesterol and 0.5% sodium cholate(w/w) which was modified from the formula of the American Institute of Nutrition-76(AIN-76) diet. Rats in treatment groups were fed with above diet supplemented with 0.1% naringin(N-0.1) or 0.2% naringin(N-0.2) on the weight to weight basis, respectively. The supplementation of naringin did not induce any significant difference on the final body weight, gain of body weight, the amount of feed intake and the feed efficiency of rats in between control and treatment groups. In addition the levels of glucose, total protein, albumin, globulin and albumin/globulin(A/G) ratio in sera of rats showed no significant differences between control and treatment groups. The levels of total cholesterol(TC) and low density lipoprotein-cholesterol(LDL-C)in sera of rats in both N-0.1 and N-0.2 groups were significantly lower than in C group(p<0.05). The levels of high density lipoprotein-cholesterol(HDL-C) were significantly higher in both N-0.1 and N-0.2 groups than in C group(p<0.05). The values of atherogenic index(AI) were significantly lower in both N-0.1 and N-0.2 groups than in C group(p<0.05). The levels of triglyceride in sera of rats showed no significant differences between control and treatment groups. The values of AST and ALT were significantly lower in both N-0.1 and N-0.2 groups than in C group(p<0.05). Therefore the supplementation of naringin to high fat diet in rats reduced effectively the serum lipid levels such as TC and LDL-C and AI which were regarded as to cause the cardiovascular diseases, and moreover it elevated the HDL-C value effectively which was regarded to protect cardiovascular diseases.

키워드

참고문헌

  1. Ajay M, Gilani AH, Mustafa MR. Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta. Life Sci 2003; 74: 603-612 https://doi.org/10.1016/j.lfs.2003.06.039
  2. American Institute of Nutrition : Report of American Institue of Nutrition Ad Hoc Committee on Standards for Nutritional Studies. J Nutr 1977; 107:1340-1348
  3. Badary OA, Abdel-Maksoud S, Ahmed WA, Owieda GH. Naringenin attenuates cisplatin nephrotoxicity in rats. Life Sci 2005; 76: 2125-2135 https://doi.org/10.1016/j.lfs.2004.11.005
  4. Bok SH, Lee SH, Park YB, Bae KH, Son KH, Jeong TS, Choi MS. Plasma and hepatic cholesterol and hepatic activities of 3-hydroxy-3-methyl-glutaryl-CoA reductase and Acyl CoA : cholesterol transferase are lower in rats fed citrus peel extract or a mixture of citrus bioflavonoids. J Nutr 1999; 129: 1182-1185
  5. Bok SH, Shin YW, Bae KH, Jeong TS, Kwon YK, Park YB, Choi MS. Effects of naringin and lovastatin on plasma and hepatic lipids in high fat and high-cholesterol fed rats. Nutr Res 2000; 20: 1007-1015 https://doi.org/10.1016/S0271-5317(00)00191-3
  6. Borradaile NM, de Dreu LE, Barrett PHR, Behrsin CD, Huff MW. Hepatoyte apoB-containing lipoprotein secretion is decresed by the grapefruit flavonoid, naringenin, via inhibition of MTP-mediated microsomal triglyceride accumulation. Biochemistry 2003; 42: 1283-1291 https://doi.org/10.1021/bi026731o
  7. Choi MS, Do KM, Park YB, Jeon SM, Jeong TS, Lee YK, Lee MK, Bok SH. Effect of naringin supplementation on cholesterol metabolism and antioxidant status in rats fed high cholesterol with different levels of vitamin E. Ann Nutr Metab 2001; 45: 193-201 https://doi.org/10.1159/000046729
  8. Cook NC, Samman S. Flavonoids - Chemistry, metabolism, cardioprotective effects, and dietary sources. J Nutr Biochem 1996; 7: 66-76 https://doi.org/10.1016/0955-2863(95)00168-9
  9. Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ. Inhibition of microsomal trigleride transfer protein in familial hypercholesterolemia. New Engl J Med 2007; 356: 148-156 https://doi.org/10.1056/NEJMoa061189
  10. Di Carlo G, Mascolo N, Izzo AA, Capasso F. Flavonoids: Old and new aspects of a class of natural therapeutic drugs. Life Sci 1999; 65: 337-353 https://doi.org/10.1016/S0024-3205(99)00120-4
  11. Dunnett CW. A multiple comparison procedure for comparing several treatments with a control. Am Stat Assoc J 1955; 50: 1096-1121 https://doi.org/10.2307/2281208
  12. Edenharder R, Gr$\ddot{u}$nhage D. Free radical scavenging abilities of flavonoids as mechanism of protection against mutagenicity induced by tert-butyl hydroxide or cumene hydroxide in Salmonella typhimurium TA102. Mutation Res 2003; 540: 1-18 https://doi.org/10.1016/S1383-5718(03)00114-1
  13. Ekambaram G, Rajendran P, Magesh V, Sakthisekaran. Naringin reduces tumor size and weight lost in N-methyl-N'- nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats. Nutr Res 2008; 28: 106-112 https://doi.org/10.1016/j.nutres.2007.12.002
  14. Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res 2004; 24: 851-874 https://doi.org/10.1016/j.nutres.2004.07.005
  15. Friewald WT, Levy RI, Fredrickson DS. Estimation of concentration of low density lipoprotein cholesterol without use of the preparation of ultracentrifuge. Clin Chem 1972; 28: 499-502
  16. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. Am J Med 1977; 62: 707-714 https://doi.org/10.1016/0002-9343(77)90874-9
  17. Griffiths LA, Smith GE. Metabolism of apigenin and related compounds in the rat. Biochem J 1972; 128: 901-911
  18. Haglund O, Luostarinen R, Wallin R, Wibell L, Saldeen T. The effects of fish oil on triglyceride, cholesterol, fibrinogen and malondialdehyde in humans supplemented with vitamin E. J Nutr 1991; 121: 165-169
  19. Havsteen BH. The biochemistry and medical significance of the flavonoids. Phamacol Therap 2002; 96: 67-202 https://doi.org/10.1016/S0163-7258(02)00298-X
  20. Hollman PCH. Bioavailability of flavonoids. Eur J Clin Nutr 1997; 51(Suppl 1):S66-S69 https://doi.org/10.1080/10408399709527799
  21. Holmes DL. Clinical laboratory animal medicine. Ames: Iowa State University Press 1984: 110-111
  22. Janbaz KH, Saeed SA, Gilani AH. Protective effect of rutin on paracetamol- and $CCl_{4}$-induced hepatotoxicity in rodents. Fitoterapia 2002; 73: 557-563 https://doi.org/10.1016/S0367-326X(02)00217-4
  23. Jeon SM, Park YB, Choi MS. Antihypercholesterolemic property of naringin alters plasma and tissue lipids, cholesterolregulating enzymes, fecal sterol and tissue morphology in rabbits. Clin Nutr 2004; 23: 1025-1034 https://doi.org/10.1016/j.clnu.2004.01.006
  24. Jung UJ, Lee MK, Park YB, Kang MA, Choi MS. Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice. International J Biochem Cell Biol 2006; 38: 1134-1145 https://doi.org/10.1016/j.biocel.2005.12.002
  25. Kannel WB, Castelli WP, Gordon T, McNamara PM. Serum cholesterol, lipoproteins, and the risk of coronary heart disease. Ann Intern Med 1971; 74: 1-12
  26. Kim KT, Moon SH, Yeo EJ, Park YS, Han YS, Nah SY, Lee NG, Paik HD. Inhibitory effect of 7-O-butyl naringenin on growth of Helicobacter pylori ATCC 26695. Food Sci Biotechnol 2006; 15: 466-468
  27. Kim SY, Kim HJ, Lee MK, Jeon SM, Do KM, Kwon EY, Cho YY, Kim DJ, Jeong KS, Park YB, Ha TY, Choi MS. Naringin time-dependently lowers hepatic cholesterol biosynthesis and plasma cholesterol in rats fed high-fat and high-cholesterol diet. J Medicinal Food 2006; 9: 582-586 https://doi.org/10.1089/jmf.2006.9.582
  28. Kobayashi S, Konishi Y. Transepithelial transport of flavanone in intestinal Caco-2 cell monolayers. Biochem Biophys Res Commun 2008; 368: 23-29 https://doi.org/10.1016/j.bbrc.2007.12.185
  29. Manach C, Scalbert A, Morand C, R$\acute{e}m$\acute{e}$sy C, Jim$\acute{e}$nez L. Polyphenols: food and bioavailability. Am J Clin Nutr 2004; 79: 727-747
  30. Martin MJ, Marhuenda E, P$\acute{e}$rez-Guerrero C, Franco JM. Antiulcer effect of naringin on gastric lesions induced by ethanol in rats. Pharmacology 1999; 49: 144-150 https://doi.org/10.1159/000139228
  31. Mattson FH, Erickson BA, Kligman AM. Effect of dietary cholesterol on serum cholesterol in man. Am J Clin Nutr 1972; 25: 589-594
  32. Mercer LD, Kelly BL, Horne MK, Beart PM. Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures. Biochem Pharmacol 2005; 69: 339-345 https://doi.org/10.1016/j.bcp.2004.09.018
  33. Mitruka BM, Rawnsley HM. Clinical biochemical and hematological reference values in normal experimental animals and normal humans. 2nd ed New York: Masson Publising USA, Inc 1981: 57-166
  34. Moon YJ, Wang X, Morris ME. Dietary flavonoids: Effects on xenobiotic and carcinogen metabolism. Toxicol in vitro 2006; 20: 187-210 https://doi.org/10.1016/j.tiv.2005.06.048
  35. Mott GE, Jackson EM, McMahan CA, McGill HC Jr. Dietary cholesterol and type of fat differentially affect cholesterol metabolism and atherosclerosis in baboons. J Nutr 1992; 122: 1397-1406
  36. Norum KR. Dietary fat and blood lipids. Nutr Rev 1992; 50: 30-37
  37. Ortu$\tilde{n}$o A, B$\acute{a}$idez A, G$\acute{o}$mez P, Arcas MC, Porras I, Garc$\acute{i}$a- Lid$\acute{o}$n, Del R$\acute{i}$o JA. Citrus paradisi and Citrus sinensis flavonoids: Their influence in the defence mechanism against Penicillium digitatum. Food Chem 2006; 98: 351-358 https://doi.org/10.1016/j.foodchem.2005.06.017
  38. Packard CJ, McKinney L, Carr K, Shepherd J. Cholesterol feeding increases low density lipoprotein synthesis. J Clin Invest 1983; 72: 45-51 https://doi.org/10.1172/JCI110983
  39. Peluso MR. Flavonoids attenuate cardiovascular disease, inhibit phosphodiesterase, and modulate lipid homeostasis in adipose tissue and liver. Exp Biol Med 2006; 231: 1287-1299
  40. Peterson J, Dwyer J. Flavonoids: Dietary occurrence and biochemical activity. Nutr Res 1998; 18: 1995-2018 https://doi.org/10.1016/S0271-5317(98)00169-9
  41. Punithavathi VR, Anuthama R, Stanely Mainzen Prince P. Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats. J Applied Toxicol 2008; 28: 806-813 https://doi.org/10.1002/jat.1343
  42. Rajadurai M, Stanely Mainzen Prince P. Preventive effect of naringin on cardiac markers, electrocardiographic patterns and lysomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats. Toxicology 2007; 230: 178-188 https://doi.org/10.1016/j.tox.2006.11.053
  43. Ribeiro IA, Rocha J, Sepodes B, Mota-Filipe H, Ribeiro MH. Effect of naringin enzymatic hydrolysis towards naringenin on the anti-inflammatory activity of both compounds. J Mol Catal B: Enzymatic 2008; 52-53: 13-18 https://doi.org/10.1016/j.molcatb.2007.10.011
  44. Reshef N, Hayari Y, Goren C, Boaz M, Madar Z, Knobler H. Antihypertensive effect of sweetie fruit in patients with stage I hypertension. Am J Hypertens 2005; 18: 1360-1363 https://doi.org/10.1016/j.amjhyper.2005.05.021
  45. Rice-Evans CA, Miller NJ, Paganga G. Structure-Antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20: 933-956 https://doi.org/10.1016/0891-5849(95)02227-9
  46. Russ M, Martinez R, Ali H, Steimle P. Naringenin is a novel inhibitor of Dictyostelium cell proliferation and cell migration. Biochem Biophys Res Commun 2006; 345: 516-522 https://doi.org/10.1016/j.bbrc.2006.04.047
  47. Santos KFR, Oliveira TT, Nagem TJ, Pinto AS, Oliveira MGA. Hypolipidaemic effects of naringenin, rutin, nicotinic acid and their associations. Phamacol Res 1999; 40: 493-496 https://doi.org/10.1006/phrs.1999.0556
  48. Seo HJ, Jeong KS, Lee MK, Park YB, Jung UJ, Kim HJ, Choi MS. Role of naringin supplement in regulation of lipid and ethanol metabolism in rats. Life Sci 2003; 73: 933-946 https://doi.org/10.1016/S0024-3205(03)00358-8
  49. Shin YW, Bok SH, Jeong TS, Bae KH, Jeong NH, Choi MS, Lee SH, Park YB. Hypocholesterolemic effect of naringin associated with hepatic cholesterol regulating enzyme changes in rats. Int J Vitam Nutr Res 19999; 69: 341-347 https://doi.org/10.1024/0300-9831.69.5.341
  50. Singh D, Chander V, Chopra K. Protective effect of naringin, a bioflavonoid on glycerol-induced acute renal failure in rat kidney. Toxicology 2004; 201: 143-151 https://doi.org/10.1016/j.tox.2004.04.018
  51. Spady DK, Woollett LA, Dietschy JM. Regulation of plasma LDL-cholesterol levels by dietary cholesterol and fatty acids. Annu Rev Nutr 1993; 13: 355-381 https://doi.org/10.1146/annurev.nu.13.070193.002035
  52. Steinberg D. The rediscovery of high density lipoprotein: a negative risk factor in atherosclerosis. Eur J Clin Invest 1978; 8: 107-109 https://doi.org/10.1111/j.1365-2362.1978.tb00821.x
  53. Suh I, Shaten J, Cutler JA, Kuller LH. Alcohol use and mortality from coronary heart disease: The role of highdensity lipoprotein cholesterol. Ann Intern Med 1991; 11: 881-887
  54. Tripoli E, La Guardia M, Giammanco S, Di Majo D, Giammanco M. Citrus flavonoids: Molecular structure, biological activity and nutritional propertied: A review. Food Chem 2007; 104: 466-479 https://doi.org/10.1016/j.foodchem.2006.11.054
  55. Vanamala J, Reddivari L, Yoo KS, Pike LM, Patil BS. Variation in the content of bioactive flavonoids in different brands of orange and grapefruit juices. J Food Comp Anal 2006; 19: 157-166 https://doi.org/10.1016/j.jfca.2005.06.002
  56. Wilcox LJ, Borradaile NM, de Dreu LE, Huff MW. Secretion of hepatocyte apoB is inhibited by the flavonoids, naringin and hesperetin, via reduced activity and expression of ACAT2 and MTP. J Lipid Res 2001; 42: 725-734
  57. Wilcox LJ, Borradaile NM, Huff MW. Antiatherogenic properties of naringenin, a citrus flavonoid. Cardiovasc Drug Rev 1999; 17: 160-178
  58. Zbarsky V, Datla KP, Parkar S, Rai DK, Aruoma OI, Dexter DT. Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson's disease. Free Radic Res 2005; 39: 1119-1125 https://doi.org/10.1080/10715760500233113
  59. 김형진, 송시환, 하창수, 한상섭. 사육밀도가 Sprague- Dawley 랫드의 성장 및 각종 생리치에 미치는 영향. 한국실험동물학회지 1993; 9: 71-82
  60. 송창우, 황화선, 한상섭. Ktc: SD 랫드의 주령에 따른 기초 연구 I. 체중변화, 혈액·혈액생화학적 변화 및 뇨분석. 한국실험동물학회지 1990; 6:33-43
  61. 이삼열, 정윤섭, 권오헌, 송경순. 임상병리검사법 7판 서울: 연세대학교 출판부 2000: 224-315
  62. 이지현, 김영소, 이종길, 이혁구, 한성순. 수종 flavonoid의 항허피스바이러스효과. 생약학회지 1999; 30: 34-39
  63. 전혜린, 정연심, 김형일, 정혁, 이수천. 운동과 naringin 첨가 식이가 흰쥐의 에너지 대사와 항산화 방어기전에 미치는 영향. 한국체육학회지(자연과학편) 2006; 45: 389-396