Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibitory Effects of Functional Sujeonggwa (Cinnamon Drink) on Lipid Peroxidation and DNA Damage in Diet-Induced Hypercholesterolemic ApoE Knockout Mice

고콜레스테롤혈증 ApoE Knockout 마우스에서 기능성 수정과의 지질과산화 및 산화적 DNA 손상 억제 효과

  • Park, Eunju (Department of Food and Nutrition, Kyungnam University) ;
  • Baek, Aran (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University) ;
  • Kim, Mijeong (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University) ;
  • Lee, Seon Woo (Department of Food and Nutrition, Kyungnam University) ;
  • Lee, Eunji (Department of Food and Nutrition, Kyungnam University) ;
  • Choi, Mi-Joo (Department of Food and Nutrition, Kyungnam University) ;
  • Lee, Jeehyun (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University) ;
  • Song, Yeong Ok (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University)
  • 박은주 (경남대학교 식품영양학과) ;
  • 백아란 (부산대학교 식품영양학과 및 김치연구소) ;
  • 김미정 (부산대학교 식품영양학과 및 김치연구소) ;
  • 이선우 (경남대학교 식품영양학과) ;
  • 이은지 (경남대학교 식품영양학과) ;
  • 최미주 (경남대학교 식품영양학과) ;
  • 이지현 (부산대학교 식품영양학과 및 김치연구소) ;
  • 송영옥 (부산대학교 식품영양학과 및 김치연구소)
  • Received : 2014.07.14
  • Accepted : 2014.07.25
  • Published : 2014.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

The recipe for sujeonggwa, a Korean traditional sweet drink containing cinnamon, ginger, sugar, or honey, was modified by replacing sugar with alternative sweeteners [stevia or short-chain frutooligosaccharide (scFOS)] in order to improve the health functionality of sujeonggwa. The aim of this study was to evaluate the effects of modified sujeonggwa on lipid peroxidation and oxidized DNA damage in diet-induced hypercholesterolemic ApoE knockout mice. Hypercholesterolemia was induced in 6-week-old male mice by administration of a high cholesterol diet (1.25% cholesterol, 0.5% cholic acid, and 10% coconut oil) for 4 weeks, after which mice were divided into five groups: sucrose solution-fed control group, sujeonggwa containing sucrose group, sucrose+stevia group, sucrose+stevia+scFOS group, and commercially available sujeonggwa group as a positive control. After 6 weeks, sujeonggwa supplementation resulted in reduced hepatic thiobarbituric acid reactive substances (TBARS), regardless of sweetener type. However, reduction of hepatic TBARS by commercially available sujeonggwa was insignificant. Both endogenous and $H_2O_2$-induced DNA damage in hepatocytes and splenocytes were significantly reduced only in the sujeonggwa containing stevia group compared to the sucrose-fed control group. There were no significant effects of sujeonggwa supplementation on total radical trapping potential, lipid peroxidation, or DNA damage in blood. These results suggest that sujeonggwa has protective effects against hepatic lipid peroxidation and DNA damage in hepatocytes or splenocytes from diet-induced hypercholesterolemic ApoE knockout mice, and the type of sweetener should be modified to improve the health benefits of sujeonggwa.

본 연구는 전통 음청류인 수정과의 세계화 일환으로 대체당을 사용하여 관능성이 탁월한 기능성 수정과 음료를 개발한 후, 개발된 수정과 음료의 항산화 및 산화적 DNA 손상억제 효능을 살펴보고자 하였다. 고콜레스테롤식이 공급으로 고콜레스테롤혈증이 유발된 10주령의 ApoE KO 마우스를 대조군인 설탕물 섭취군(Control), 설탕 첨가 수정과 음료 섭취군(Sucrose), 스티비아 첨가 수정과 음료 섭취군(Stevia), scFOS 첨가 수정과 음료 섭취군(scSFO), 그리고 양성대조군으로 시판 수정과를 섭취시킨 군(Positive control)으로 나누어 실험 식이를 6주간 공급한 후, 혈장 TRAP, 혈장 및 간의 TBARS, 백혈구, 간세포 및 비장세포의 내재적 또는 산화적 스트레스로 인한 DNA 손상 정도를 측정하였다. 모든 군에서 체중 증가량, 식이 섭취량, 조직 무게는 유의적 차이가 없었다. 간 TBARS 농도는 설탕물을 섭취한 대조군에 비해 설탕의 농도를 달리하여 제조한 수정과 음료군인 sucrose군, stevia 첨가군, 그리고 scFOS 첨가군의 TBARS 농도가 유의적으로 감소하여 수정과의 지질과산화 억제 효과를 확인할 수 있었다. 설탕을 줄이는 대신 stevia를 첨가하여 제조한 기능성 수정과 섭취군에서 설탕물만을 섭취한 대조군에 비해 간, 비장세포의 내재적(endogenous) 또는 $H_2O_2$로 유도된 산화적 DNA 손상에 대한 억제 효과가 있는 것으로 나타났다. 백혈구의 DNA 손상의 경우 stevia군에서 대조군에 비해 감소하는 경향을 보여주었으나 통계적 유의성은 없었다. 시판 수정과의 경우 간세포의 내재적 DNA 손상만을 억제하는 효능이 있는 것으로 나타났으며, 설탕만으로 제조한 수정과나 scFOS가 첨가된 수정과 섭취군의 경우 내재적 또는 $H_2O_2$로 유도된 산화적 DNA 손상이 대조군에 비해 감소하는 경향을 보여주었으나 유의성은 없었다. 이상 본 연구의 결과, 고콜레스테롤혈증이 유발된 ApoE KO 마우스에서 수정과의 보충 섭취는 간 지질과산화를 개선시키고 stevia 첨가 수정과의 경우 간 및 비장에서 DNA 손상 억제효과가 있음을 확인할 수 있었다. 본 연구 결과가 수정과의 세계화에 기여할 수 있기를 기대하며, 향후 본 연구를 기반으로 한 분자생물학적 수준의 기전 연구가 필요하다고 사료된다.

Keywords

References

  1. Stranahan AM, Cutler RG, Button C, Telljohann R, Mattson MP. 2011. Diet-induced elevations in serum cholesterol are associated with alterations in hippocampal lipid metabolism and increased oxidative stress. J Neurochem 118: 611-615. https://doi.org/10.1111/j.1471-4159.2011.07351.x
  2. Sudhahar V, Kumar SA, Mythili Y, Varalakshmi P. 2007. Remedial effect of lupeol and its ester derivative on hypercholesterolemia-induced oxidative and inflammatory stresses. Nutr Res 27: 778-787. https://doi.org/10.1016/j.nutres.2007.09.012
  3. Folkmann JK, Loft S, Moller P. 2007. Oxidatively damaged DNA in aging dyslipidemic $ApoE^{-}/^{-}$ and wild-type mice. Mutagenesis 22: 105-110. https://doi.org/10.1093/mutage/gel059
  4. Dalboni SP, Campagnaro BP, Tonini CL, Vasquez EC, Meyrelles SS. 2012. The concurrence of hypercholesterolemia and aging promotes DNA damage in apolipoprotein E-deficient mice. Open J Blood Dis 2: 51-55. https://doi.org/10.4236/ojbd.2012.23010
  5. Kannappan S, Jayaraman T, Rajasekar P, Ravichandran MK, Anuradha CV. 2006. Cinnamon bark extract improves glucose metabolism and lipid profile in the fructose-fed rat. Singapore Med J 47: 858-863.
  6. Huang B, Yuan HD, Kim DY, Quan HY, Chung SH. 2011. Cinnamaldehyde prevents adipocyte differentiation and adipogenesis via regulation of peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR{\gamma}$) and AMP-activated protein kinase (AMPK) pathways. J Agric Food Chem 59: 3666-3673. https://doi.org/10.1021/jf104814t
  7. Ali BH, Blunden G, Tanira MO, Nemmar A. 2008. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol 46: 409-420. https://doi.org/10.1016/j.fct.2007.09.085
  8. Dugasani S, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN. 2010. Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol. J Ethnopharmacol 127: 515-520. https://doi.org/10.1016/j.jep.2009.10.004
  9. Oboh G, Akinyemi AJ, Ademiluyi AO, Adefegha SA. 2010. Inhibitory effect of aqueous extract of two varieties of ginger on some key enzymes linked to type-2 diabetes in vitro. J Food Nutr Res 49: 14-20.
  10. Choudhury D, Das A, Bhattacharya A, Chakrabarti G. 2010. Aqueous extract of ginger shows antiproliferative activity through disruption of microtubule network of cancer cells. Food Chem Toxicol 48: 2872-2880. https://doi.org/10.1016/j.fct.2010.07.020
  11. Fuhrman B, Rosenblat M, Hayek T, Coleman R, Aviram M. 2000. Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice. J Nutr 130: 1124-1131.
  12. Park JE, Cha YS. 2010. Stevia rebaudiana Bertoni extract supplementation improves lipid and carnitine profiles in C57BL/6J mice fed a high-fat diet. J Sci Food Agric 90: 1099-1105. https://doi.org/10.1002/jsfa.3906
  13. Choi SY, Jang EG, Hwang IK. 2005. The sensory characteristics and estimation of shelf-life by Q10 values with mixtures of high-intensity sweeteners for beverage during storage. Korean J Food Cookery Sci 21: 235-242.
  14. Cho BO, Ryu HW, So Y, Cho JK, Woo HS, Jin CH, Seo KI, Park JC, Jeong IY. 2013. Anti-inflammatory effect of austroinulin and 6-O-acetyl-austroinulin from Stevia rebaudiana in lipopolysaccharide-stimulated RAW264.7 macrophages. Food Chem Toxicol 62: 638-644. https://doi.org/10.1016/j.fct.2013.09.011
  15. Bornet FR, Brouns F, Tashiro Y, Duvillier V. 2002. Nutritional aspects of short-chain fructooligosaccharides: natural occurrence, chemistry, physiology and health implications. Dig Liver Dis 34: S111-S120. https://doi.org/10.1016/S1590-8658(02)80239-0
  16. Bouhnik Y, Achour L, Paineau D, Riottot M, Attar A, Bornet F. 2007. Four-week short chain fructo-oligosaccharides ingestion leads to increasing fecal bifidobacteria and cholesterol excretion in healthy elderly volunteers. Nutr J 6: 42-48. https://doi.org/10.1186/1475-2891-6-42
  17. Agheli N, Kabir M, Berni-Canani S, Petitjean E, Boussairi A, Luo J, Bornet F, Slama G, Rizkalla SW. 1998. Plasma lipids and fatty acid synthase activity are regulated by shortchain fructo-oligosaccharides in sucrose-fed insulin-resistant rats. J Nutr 128: 1283-1288.
  18. Bush RS, Milligan LP. 1971. Study of the mechanism of inhibition of ketogenesis by propionate in bovine liver. Can J Anim Sci 51: 121-127. https://doi.org/10.4141/cjas71-016
  19. Seo JH, Sung TH, Kim MR. 2002. Quality characteristics of Sujongkwa. J East Asian Soc Dietary Life 12: 370-378.
  20. Kusunoki J, Hansoty DK, Aragane K, Fallon JT, Badimon JJ, Fisher FA. 2001. Acyl-CoA: cholesterol acyltransferase inhibition reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 103: 2604-2609. https://doi.org/10.1161/01.CIR.103.21.2604
  21. Korean Statistical Information Service. http://kosis.kr/statHtml/statHtml.do?orgId=117&tblId=DT_11702_N221&vw_cd=&list_id=&scrId=&seqNo=&lang_mode=ko&obj_var_id=&itm_id=&conn_path=K1&path= (accessed Jan 2014).
  22. Rice-Evans C, Miller NJ. 1994. Total antioxidant status in plasma and body fluids. Methods Enzymol 234: 279-293. https://doi.org/10.1016/0076-6879(94)34095-1
  23. Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95: 351-358. https://doi.org/10.1016/0003-2697(79)90738-3
  24. Singh NP, McCoy MT, Tice RR, Schneider EL. 1988. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175: 184-191. https://doi.org/10.1016/0014-4827(88)90265-0
  25. Beltowski J, Wojcicka G, Gorny D, Marciniak A. 2000. The effect of dietary-induced obesity on lipid peroxidation, antioxidant enzymes and total plasma antioxidant capacity. J Physiol Pharmacol 51: 883-896.
  26. Junqueira VBC, Barros SBM, Chan SS, Rodrigues L, Giavarotti L, Abud RL, Deucher GP. 2004. Aging and oxidative stress. Mol Aspects Med 25: 5-16. https://doi.org/10.1016/j.mam.2004.02.003
  27. Karbiner MS, Sierra L, Minahk C, Fonio MC, Bruno MP, Jerez S. 2013. The role of oxidative stress in alterations of hematological parameters and inflammatory markers induced by early hypercholesterolemia. Life Sci 93: 503-508. https://doi.org/10.1016/j.lfs.2013.08.003
  28. Vaca CE, Wilhelm J, Harms-Ringdahl M. 1988. Interaction of lipid peroxidation products with DNA. A review. Mutat Res 195: 137-149. https://doi.org/10.1016/0165-1110(88)90022-X
  29. Kwon EY, Cho YY, Do GM, Kim HJ, Jeon SM, Park YB, Lee MK, Min TS, Choi MS. 2009. Actions of ferulic acid and vitamin E on prevention of hypercholesterolemia and atherogenic lesion formation in apolipoprotein E-deficient mice. J Med Food 12: 996-1003. https://doi.org/10.1089/jmf.2009.0105
  30. Sadaba LM, Fernandez-Robredo P, Rodriguez JA, Garcia-Layana A. 2008. Antioxidant effects of vitamins C and E, multivitamin-mineral complex and flavonoids in a model of retinal oxidative stress: the ApoE-deficient mouse. Exp Eye Res 86: 470-479. https://doi.org/10.1016/j.exer.2007.11.020
  31. Azab KSh, Mostafa AH, Ali EM, Abdel-Aziz MA. 2011. Cinnamon extract ameliorates ionizing radiation-induced cellular injury in rats. Ecotoxicol Environ Saf 74: 2324-2329. https://doi.org/10.1016/j.ecoenv.2011.06.016
  32. Ranjbar A, Ghaseminejhad S, Takalu H, Baiaty A, Rahimi F, Abdollahi M. 2008. Anti oxidative stress potential of cinnamon (Cinnamomum zeylanicum) in operating room personnel; a before/after cross sectional clinical trial. Int J Pharmacol 3: 482-486.
  33. Ahmed RS, Suke SG, Seth V, Chakraborti A, Tripathi AK, Banerjee BD. 2008. Protective effects of dietary ginger (Zingiber officinales Rosc.) on lindane-induced oxidative stress in rats. Phytother Res 22: 902-906. https://doi.org/10.1002/ptr.2412
  34. Kim MY, Cheong SH, Lee JH, Kim MJ, Sok DE, Kim MR. 2010. Spirulina improves antioxidant status by reducing oxidative stress in rabbits fed a high-cholesterol diet. J Med Food 13: 420-426. https://doi.org/10.1089/jmf.2009.1215
  35. Mercer JR, Yu E, Figg N, Cheng KK, Prime TA, Griffin JL, Masoodi M, Vidal-Puig A, Murphy MP, Bennett MR. 2012. The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in $ATM^{+/-}/ApoE^{-/-}$ mice. Free Radic Biol Med 52: 841-849. https://doi.org/10.1016/j.freeradbiomed.2011.11.026
  36. King AA, Shaughnessy DT, Mure K, Leszczynska J, Ward WO, Umbach DM, Xu Z, Ducharme D, Taylor JA, Demarini DM, Klein CB. 2007. Antimutagenicity of cinnamaldehyde and vanillin in human cells: global gene expression and possible role of DNA damage and repair. Mutat Res 616: 60-69. https://doi.org/10.1016/j.mrfmmm.2006.11.022
  37. Yang G, Zhong L, Jiang L, Geng C, Cao J, Sun X, Liu X, Chen M, Ma Y. 2011. 6-Gingerol prevents patulin-induced genotoxicity in HepG2 cells. Phytother Res 25: 1480-1485. https://doi.org/10.1002/ptr.3446
  38. Ghanta S, Banerjee A, Poddar A, Chattopadhyay S. 2007. Oxidative DNA damage preventive activity and antioxidant potential of Stevia rebaudiana (Bertoni) Bertoni, a natural sweetener. J Agric Food Chem 55: 10962-10967. https://doi.org/10.1021/jf071892q