Nutrition Research and Practice

  • 제18권2호
  • /
  • Pages.194-209
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  • 2024
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  • 1976-1457(pISSN)
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  • 2005-6168(eISSN)
한국영양학회 (The Korean Nutrition Society)
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Ellagic acid, a functional food component, ameliorates functionality of reverse cholesterol transport in murine model of atherosclerosis

  • Sin-Hye Park (Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University) ;
  • Min-Kyung Kang (Department of Food and Nutrition, Andong National University) ;
  • Dong Yeon Kim (Department of Food and Nutrition, Andong National University) ;
  • Soon Sung Lim (Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University) ;
  • Il-Jun Kang (Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University) ;
  • Young-Hee Kang (Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University)
  • 투고 : 2023.11.16
  • 심사 : 2024.02.08
  • 발행 : 2024.04.01
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초록

BACKGROUND/OBJECTIVES: High levels of plasma low-density lipoprotein (LDL) cholesterol are an important determinant of atherosclerotic lesion formation. The disruption of cholesterol efflux or reverse cholesterol transport (RCT) in peripheral tissues and macrophages may promote atherogenesis. The aim of the current study was to examine whether bioactive ellagic acid, a functional food component, improved RCT functionality and high-density lipoprotein (HDL) function in diet-induced atherogenesis of apolipoproteins E (apoE) knockout (KO) mice. MATERIALS/METHODS: Wild type mice and apoE KO mice were fed a high-cholesterol Paigen diet for 10 weeks to induce hypercholesterolemia and atherosclerosis, and concomitantly received 10 mg/kg ellagic acid via gavage. RESULTS: Supplying ellagic acid enhanced induction of apoE and ATP-binding cassette (ABC) transporter G1 in oxidized LDL-exposed macrophages, facilitating cholesterol efflux associated with RCT. Oral administration of ellagic acid to apoE KO mice fed on Paigen diet improved hypercholesterolemia with reduced atherogenic index. This compound enhanced the expression of ABC transporters in peritoneal macrophages isolated from apoE KO mice fed on Paigen diet, indicating increased cholesterol efflux. Plasma levels of cholesterol ester transport protein and phospholipid transport protein involved in RCT were elevated in mice lack of apoE gene, which was substantially reduced by supplementing ellagic acid to Paigen diet-fed mice. In addition, ellagic acid attenuated hepatic lipid accumulation in apoE KO mice, evidenced by staining of hematoxylin and eosin and oil red O. Furthermore, the supplementation of 10 mg/kg ellagic acid favorably influenced the transcriptional levels of hepatic LDL receptor and scavenger receptor-B1 in Paigen diet-fed apoE KO mice. CONCLUSION: Ellagic acid may be an athero-protective dietary compound encumbering diet-induced atherogenesis though improving the RCT functionality.

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과제정보

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1A6A1A03044501) and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2022R1A2B5B01001861).

참고문헌

  1. Frostegard J. Immunity, atherosclerosis and cardiovascular disease. BMC Med 2013;11:117.
  2. Valanti EK, Dalakoura-Karagkouni K, Siasos G, Kardassis D, Eliopoulos AG, Sanoudou D. Advances in biological therapies for dyslipidemias and atherosclerosis. Metabolism 2021;116:154461.
  3. Glass CK, Witztum JL. Atherosclerosis. the road ahead. Cell 2001;104:503-16.
  4. Soliman GA. Dietary cholesterol and the lack of evidence in cardiovascular disease. Nutrients 2018;10:780.
  5. Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 2013;40:195-211.
  6. Ohashi R, Mu H, Wang X, Yao Q, Chen C. Reverse cholesterol transport and cholesterol efflux in atherosclerosis. QJM 2005;98:845-56.
  7. Joyce CW, Amar MJ, Lambert G, Vaisman BL, Paigen B, Najib-Fruchart J, Hoyt RF Jr, Neufeld ED, Remaley AT, Fredrickson DS, et al. The ATP binding cassette transporter A1 (ABCA1) modulates the development of aortic atherosclerosis in C57BL/6 and apoE-knockout mice. Proc Natl Acad Sci U S A 2002;99:407-12.
  8. Rohatgi A. Reverse cholesterol transport and atherosclerosis. Arterioscler Thromb Vasc Biol 2019;39:2-4.
  9. Getz GS, Reardon CA. Apoprotein E and reverse cholesterol transport. Int J Mol Sci 2018;19:3479.
  10. Wang HH, Garruti G, Liu M, Portincasa P, Wang DQ. Cholesterol and lipoprotein metabolism and atherosclerosis: recent advances in reverse cholesterol transport. Ann Hepatol 2017;16:s27-42.
  11. Cuchel M, Rader DJ. Macrophage reverse cholesterol transport: key to the regression of atherosclerosis? Circulation 2006;113:2548-55.
  12. Wang N, Tall AR. Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux. Arterioscler Thromb Vasc Biol 2003;23:1178-84.
  13. Dallinga-Thie GM, Dullaart RP, van Tol A. Concerted actions of cholesteryl ester transfer protein and phospholipid transfer protein in type 2 diabetes: effects of apolipoproteins. Curr Opin Lipidol 2007;18:251-7.
  14. Shrestha S, Wu BJ, Guiney L, Barter PJ, Rye KA. Cholesteryl ester transfer protein and its inhibitors. J Lipid Res 2018;59:772-83.
  15. Luo Y, Shelly L, Sand T, Reidich B, Chang G, MacDougall M, Peakman MC, Jiang XC. Pharmacologic inhibition of phospholipid transfer protein activity reduces apolipoprotein-B secretion from hepatocytes. J Pharmacol Exp Ther 2010;332:1100-6.
  16. Dove DE, Linton MF, Fazio S. ApoE-mediated cholesterol efflux from macrophages: separation of autocrine and paracrine effects. Am J Physiol Cell Physiol 2005;288:C586-92.
  17. Oppi S, Luscher TF, Stein S. Mouse models for atherosclerosis research-which is my line? Front Cardiovasc Med 2019;6:46.
  18. Greenow K, Pearce NJ, Ramji DP. The key role of apolipoprotein E in atherosclerosis. J Mol Med (Berl) 2005;83:329-42.
  19. Meir KS, Leitersdorf E. Atherosclerosis in the apolipoprotein-E-deficient mouse: a decade of progress. Arterioscler Thromb Vasc Biol 2004;24:1006-14.
  20. Su YR, Ishiguro H, Major AS, Dove DE, Zhang W, Hasty AH, Babaev VR, Linton MF, Fazio S. Macrophage apolipoprotein A-I expression protects against atherosclerosis in ApoE-deficient mice and up-regulates ABC transporters. Mol Ther 2003;8:576-83.
  21. Derosa G, Maffioli P, Sahebkar A. Ellagic acid and its role in chronic diseases. Adv Exp Med Biol 2016;928:473-9.
  22. Larrosa M, Garcia-Conesa MT, Espin JC, Tomas-Barberan FA. Ellagitannins, ellagic acid and vascular health. Mol Aspects Med 2010;31:513-39.
  23. Lee WJ, Ou HC, Hsu WC, Chou MM, Tseng JJ, Hsu SL, Tsai KL, Sheu WH. Ellagic acid inhibits oxidized LDL-mediated LOX-1 expression, ROS generation, and inflammation in human endothelial cells. J Vasc Surg 2010;52:1290-300.
  24. Park SH, Kim JL, Lee ES, Han SY, Gong JH, Kang MK, Kang YH. Dietary ellagic acid attenuates oxidized LDL uptake and stimulates cholesterol efflux in murine macrophages. J Nutr 2011;141:1931-7.
  25. Khateeb J, Gantman A, Kreitenberg AJ, Aviram M, Fuhrman B. Paraoxonase 1 (PON1) expression in hepatocytes is upregulated by pomegranate polyphenols: a role for PPAR-gamma pathway. Atherosclerosis 2010;208:119-25.
  26. Phillips MC. Molecular mechanisms of cellular cholesterol efflux. J Biol Chem 2014;289:24020-9.
  27. Zaiou M, Arnold KS, Newhouse YM, Innerarity TL, Weisgraber KH, Segall ML, Phillips MC, Lund- Katz S. Apolipoprotein E;-low density lipoprotein receptor interaction. Influences of basic residue and amphipathic α-helix organization in the ligand. J Lipid Res 2000;41:1087-95.
  28. Zhang SH, Reddick RL, Burkey B, Maeda N. Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption. J Clin Invest 1994;94:937-45.
  29. Penson PE, Banach M. Natural compounds as anti-atherogenic agents: clinical evidence for improved cardiovascular outcomes. Atherosclerosis 2021;316:58-65.
  30. Sedighi M, Bahmani M, Asgary S, Beyranvand F, Rafieian-Kopaei M. A review of plant-based compounds and medicinal plants effective on atherosclerosis. J Res Med Sci 2017;22:30.
  31. Li RL, Wang LY, Liu S, Duan HX, Zhang Q, Zhang T, Peng W, Huang Y, Wu C. Natural flavonoids derived from fruits are potential agents against atherosclerosis. Front Nutr 2022;9:862277.
  32. Lutz M, Fuentes E, Avila F, Alarcon M, Palomo I. Roles of phenolic compounds in the reduction of risk factors of cardiovascular diseases. Molecules 2019;24:366.
  33. Rios JL, Giner RM, Marin M, Recio MC. A pharmacological update of ellagic acid. Planta Med 2018;84:1068-93.
  34. Ouimet M, Barrett TJ, Fisher EA. HDL and reverse cholesterol transport: basic mechanisms and their roles in vascular health and disease. Circ Res 2019;124:1505-18.
  35. Shen WJ, Azhar S, Kraemer FB. SR-B1: a unique multifunctional receptor for cholesterol influx and efflux. Annu Rev Physiol 2018;80:95-116.
  36. Mardones P, Quinones V, Amigo L, Moreno M, Miquel JF, Schwarz M, Miettinen HE, Trigatti B, Krieger M, VanPatten S, et al. Hepatic cholesterol and bile acid metabolism and intestinal cholesterol absorption in scavenger receptor class B type I-deficient mice. J Lipid Res 2001;42:170-80.
  37. Wang Z, Chen J, Zeng Z, Zhang Q, Du G, Guo X, Wei Y. The LOX-1 receptor ectopically expressed in the liver alleviates atherosclerosis by clearing Ox-LDL from the circulation. Mol Med 2022;28:26.
  38. Basso F, Freeman L, Knapper CL, Remaley A, Stonik J, Neufeld EB, Tansey T, Amar MJ, Fruchart-Najib J, Duverger N, et al. Role of the hepatic ABCA1 transporter in modulating intrahepatic cholesterol and plasma HDL cholesterol concentrations. J Lipid Res 2003;44:296-302.