Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
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Effects of black chokeberry on cholesterol metabolism in HepG2 cells

블랙 초크베리가 HepG2세포에서 콜레스테롤 대사에 미치는 효과

  • Lee, Sang Gil (Department of Food Science and Nutrition, Pukyong National University) ;
  • Kim, Bohkyung (Department of Food Science and Nutrition, Pusan National University)
  • 이상길 (부경대학교 식품영양학과) ;
  • 김보경 (부산대학교 식품영양학과)
  • Received : 2022.07.20
  • Accepted : 2022.08.08
  • Published : 2022.08.31
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Abstract

Black chokeberry (Aronia melanocarpa), a rich source of polyphenols, exerts hypocholesterolemic effects. However, little is known about its effects on the regulation of the hepatic cholesterol metabolism and the underlying mechanisms. In the present study, the effects of polyphenol-rich black chokeberry extract (CBE) on hepatic cholesterol metabolism were investigated by measuring the expression of genes involved in the absorption, de novo synthesis, and efflux of cholesterol in HepG2 cells. There was a significant reduction in the expression levels of genes involved in cholesterol metabolism, the low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and sterol regulatory element-binding protein 2, in CBE-treated HepG2 cells. Meanwhile, CBE increased the expression levels of genes involved in cholesterol and bile acid efflux. The expression levels of mitochondrial fatty acid oxidation genes increased, whereas those of lipogenic genes decreased following CBE treatment. These data suggest that the consumption of black chokeberry may be beneficial for the prevention of hypercholesterolemia.

본 연구에서는 폴리페놀 함유 블랙 초크베리가 콜레스테롤 대사에 미치는 영향을 HepG2 세포에서 콜레스테롤 대사 관련 유전자 발현을 측정함에 따라 조사하였다. 블랙 초크베리는 콜레스테롤 대사와 관련하여 콜레스테롤 흡수, 생합성, 유출과 관련된 유전자 발현을 조절하는 것으로 나타났다. 이는 블랙 초크베리의 혈중 콜레스테롤 저하 효과가 콜레스테롤 및 담즙 대사 관련 유전자 발현을 조절함에 의한 것으로 사료된다. 추후 블랙 초크베리 내 어떠한 생리활성물질이 콜레스테롤 대사 유전자 발현을 조절하여 이러한 효과를 나타내는 지에 대한 연구가 필요하며, 블랙 초크베리의 콜레스테롤 저하 효과를 동물 및 임상에서 기전 연구를 진행하여 천연 유래 기능성 소재로서의 블랙 초크베리의 중요성을 검증할 필요가 있을 것으로 사료된다.

Keywords

Acknowledgement

본 논문은 부산대학교 기본연구지원사업(2년)에 의하여 연구되었음으로 이에 감사드립니다.

References

  1. Abel T, Feher J. Statin therapy and muscle disorders. Orv Hetil. 150: 261-263 (2009) https://doi.org/10.1556/oh.2009.28520
  2. Brown MS, Goldstein JL. Sterol regulatory element binding proteins (SREBPs): controllers of lipid synthesis and cellular uptake. Nutr Rev. 56: S1-3; discussion S54-75 (1998)
  3. Chambers KF, Day PE, Aboufarrag HT, Kroon PA. Polyphenol effects on cholesterol metabolism via bile acid biosynthesis, CYP7A1: a review. Nutrients. 11 (2019)
  4. Chiang JY. Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms. J. Hepatol. 40: 539-551 (2004) https://doi.org/10.1016/j.jhep.2003.11.006
  5. Chung S, Gebre AK, Seo J, Shelness GS, Parks JS. A novel role for ABCA1-generated large pre-beta migrating nascent HDL in the regulation of hepatic VLDL triglyceride secretion. J. Lipid Res. 51: 729-742 (2010)
  6. Dikkers A, Tietge UJF. Biliary cholesterol secretion: More than a simple ABC. World J. Gastroenterol. 16: 5936-5945 (2010)
  7. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 343: 425-430 (1990) https://doi.org/10.1038/343425a0
  8. Groen AK, Bloks VW, Verkade H, Kuipers F. Cross-talk between liver and intestine in control of cholesterol and energy homeostasis. Mol. Aspects Med. 37:77-88 (2014) https://doi.org/10.1016/j.mam.2014.02.001
  9. Jia L, Betters JL, Yu L. Niemann-Pick C1-Like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. Annual Review of Physiology. 73: 239-259 (2011) https://doi.org/10.1146/annurev-physiol-012110-142233
  10. Jurikova T, Mlcek J, Skrovankova S, Sumczynski D, Sochor J, Hlavacova I, Snopek L, Orsavova J. Fruits of black chokeberry Aronia melanocarpa in the prevention of chronic diseases. Molecules. 22 (2017)
  11. Kashani A, Sallam T, Bheemreddy S, Mann DL, Wang Y, Foody JM. Review of side-effect profile of combination ezetimibe and statin therapy in randomized clinical trials. Am. J. Cardiol. 101: 1606-1613 (2008) https://doi.org/10.1016/j.amjcard.2008.01.041
  12. Kim B, Park Y, Wegner CJ, Bolling BW, Lee J. Polyphenol-rich black chokeberry (Aronia melanocarpa) extract regulates the expression of genes critical for intestinal cholesterol flux in Caco-2 cells. J Nutr Biochem. 24: 1564-1570 (2013) https://doi.org/10.1016/j.jnutbio.2013.01.005
  13. Lee D-H, Choi S-S, Kim B-B, Kim S-Y, Kang B-S, Lee S-J, Park H-J. Effect of alcohol-free red wine concentrates on cholesterol homeostasis: An in vitro and in vivo study. Process Biochemistry. 48: 1964-1971 (2013) https://doi.org/10.1016/j.procbio.2013.09.007
  14. Madison BB. Srebp2: A master regulator of sterol and fatty acid synthesis. J. Lipid Res. 57: 333-335 (2016) https://doi.org/10.1194/jlr.C066712
  15. Millar JS, Cuchel M. Cholesterol metabolism in humans: a review of methods and comparison of results. Curr. Opin. Lipidol. 29: 1-9 (2018) https://doi.org/10.1097/MOL.0000000000000475
  16. Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Primary Care. 40: 195-211 (2013) https://doi.org/10.1016/j.pop.2012.11.003
  17. Ontawong A, Pasachan T, Trisuwan K, Soodvilai S, Duangjai A, Pongchaidecha A, Amornlerdpison D, Srimaroeng C. Coffea arabica pulp aqueous extract attenuates oxidative stress and hepatic lipid accumulation in HepG2 cells. J. Herb. Med. 29 (2021)
  18. Quinones M, Miguel M, Aleixandre A. The polyphenols, naturally occurring compounds with beneficial effects on cardiovascular disease. Nutr. Hosp. 27: 76-89 (2012)
  19. Quinones M, Miguel M, Aleixandre A. Beneficial effects of polyphenols on cardiovascular disease. Pharmacol. Res. 68: 125-131 (2013) https://doi.org/10.1016/j.phrs.2012.10.018
  20. Ren K, Jiang T, Zhao GJ. Quercetin induces the selective uptake of HDL-cholesterol via promoting SR-BI expression and the activation of the PPARgamma/LXRalpha pathway. Food Funct. 9: 624-635 (2018) https://doi.org/10.1039/C7FO01107E
  21. Sato R. Sterol metabolism and SREBP activation. Archives of Biochemistry and Biophysics. 501: 177-181 (2010) https://doi.org/10.1016/j.abb.2010.06.004
  22. Shen WJ, Azhar S, Kraemer FB. SR-B1: a unique multifunctional receptor for cholesterol influx and efflux. Annu. Rev. Physiol. 80: 95-116 (2018) https://doi.org/10.1146/annurev-physiol-021317-121550
  23. Simonson W. Update on statin drugs for lipid disorders. Geriatr. Nurs. 39: 350-351 (2018) https://doi.org/10.1016/j.gerinurse.2018.04.016
  24. Tangney CC, Rasmussen HE. Polyphenols, inflammation, and cardiovascular disease. Curr. Atheroscler Rep. 15: 324 (2013) https://doi.org/10.1007/s11883-013-0324-x
  25. Temel RE, Brown JM. A new model of reverse cholesterol transport: enTICEing strategies to stimulate intestinal cholesterol excretion. Trends Pharmacol. Sci. 36: 440-451 (2015) https://doi.org/10.1016/j.tips.2015.04.002
  26. Tu L, Sun H, Tang M, Zhao J, Zhang Z, Sun X, He S. Red raspberry extract (Rubus idaeus L shrub) intake ameliorates hyperlipidemia in HFD-induced mice through PPAR signaling pathway. Food Chem. Toxicol. 133: 110796 (2019) https://doi.org/10.1016/j.fct.2019.110796
  27. Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Cheng S, Delling FN, Elkind MSV, Evenson KR, Ferguson JF, Gupta DK, Khan SS, Kissela BM, Knutson KL, Lee CD, Lewis TT, Liu J, Loop MS, Lutsey PL, Ma J, Mackey J, Martin SS, Matchar DB, Mussolino ME, Navaneethan SD, Perak AM, Roth GA, Samad Z, Satou GM, Schroeder EB, Shah SH, Shay CM, Stokes A, Van-Wagner LB, Wang NY, Tsao CW, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation. 143: e254-e743 (2021)
  28. Wang DQ, Portincasa P, Tso P. Transintestinal cholesterol excretion: a secondary, nonbiliary pathway contributing to reverse cholesterol transport. Hepatology. 66: 1337-1340 (2017) https://doi.org/10.1002/hep.29341
  29. Wong TY, Lin SM, Leung LK. The flavone luteolin suppresses SREBP-2 expression and post-translational activation in hepatic cells. PLoS One. 10: e0135637 (2015) https://doi.org/10.1371/journal.pone.0135637
  30. Zafra-Stone S, Yasmin T, Bagchi M, Chatterjee A, Vinson JA, Bagchi D. Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol. Nutr. Food Res. 51: 675-683 (2007) https://doi.org/10.1002/mnfr.200700002