Skip to main content

Anti-atherosclerotic effects of perilla oil in rabbits fed a high-cholesterol diet

Abstract

Anti-atherosclerosis effects of perilla oil were investigated, in comparison with lovastatin, in rabbits fed a high-cholesterol diet (HCD). Hypercholesterolemia was induced in rabbits by feeding the HCD containing 0.5% cholesterol and 1% corn oil, and perilla oil (0.1 or 0.3%) was added to the diet containing 0.5% cholesterol for 10 weeks. HCD greatly increased blood total cholesterol and low-density lipoproteins, and caused thick atheromatous plaques, covering 74% of the aortic wall. Hyper-cholesterolemia also induced lipid accumulation in the liver and kidneys, leading to lipid peroxidation. Perilla oil not only attenuated hypercholesterolemia and atheroma formation, but also reduced fat accumulation and lipid peroxidation in hepatic and renal tissues. The results indicate that perilla oil prevents atherosclerosis and fatty liver by controlling lipid metabolism, and that it could be the first choice oil to improve diet-induced metabolic syndrome.

References

  1. 1.

    Huh KB. The present status of nutrition-related diseases and its countermeasures. Kor J Nutr 1990; 23(3): 197–207.

    Google Scholar 

  2. 2.

    Lee HK. Pattern of disease incidence and nutrition in Korea. Kor J Nutr 1996; 29(4): 381–383.

    Google Scholar 

  3. 3.

    Lee YC. Hypercholesterolemia in Korea and nutritional factors. Korean Soc Lipidol Atherosc 1991; 1(1): 111–122.

    Google Scholar 

  4. 4.

    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.

    CAS  PubMed  Google Scholar 

  5. 5.

    Natio HK. Atherogenesis: current topics on etiology and risk factors. Clin Chem 1995; 41(1): 132–133.

    Google Scholar 

  6. 6.

    Bemis CE, Gorlin R, Kemp HG, Herman MV. Progression of coronary artery disease. A clinical arteriographic study. Circulation 1973; 47(3): 455–464.

    CAS  PubMed  Google Scholar 

  7. 7.

    Kannel WB, Castelli WP, Gordon T, McNamara PM. Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med 1971; 74(1): 1–12.

    CAS  PubMed  Google Scholar 

  8. 8.

    Jialal I, Devaraj S. The role of oxidized low density lipoprotein in atherogenesis. J Nutr 1996; 126(4 suppl): 1053S–1057S.

    CAS  PubMed  Google Scholar 

  9. 9.

    Glass CK, Witztum JL. Atherosclerosis. the road ahead. Cell 2001; 104(4): 503–516.

    CAS  PubMed  Google Scholar 

  10. 10.

    Blum A, Simsolo C, Hasin Y. 3-Hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitors (statins), atherosclerosis and coronary syndromes. Atherosclerosis 2004; 175(1): 1–5.

    CAS  PubMed  Google Scholar 

  11. 11.

    Larsen ML, Illingworth DR. Drug treatment of dyslipoproteinemia. Med Clin North Am 1994; 78(1): 225–245.

    CAS  PubMed  Google Scholar 

  12. 12.

    Cho JH, Lee NJ, Chai HY, Kim TM, Park JH, Kang JK, Kim YB, Hwang SY. Effect of Hwalgidan SJ-101 on atherosclerosis in hypercholesterolemic rabbits. Lab Anim Res 2005; 21(2): 149–157.

    Google Scholar 

  13. 13.

    Hong SH, Chai HY, Kim TM, Lee NJ, Kim DK, Cho JH, Park JH, Kim YB, Kang JK, Hwang SY. Therapeutic Effects of Mulberry Root-Bark (Mori radicis Cortex) Ethanol Extract on Atherosclerosis in Hypercholesterolemic Rabbits. Lab Anim Res 2005; 21(3): 273–279.

    Google Scholar 

  14. 14.

    Kim HK, Choi S, Choi H. Suppression of hepatic fatty acid synthase by feeding alpha-linolenic acid rich perilla oil lowers plasma triacylglycerol level in rats. J Nutr Biochem 2004; 15(8): 485–492.

    CAS  PubMed  Google Scholar 

  15. 15.

    Huang MZ, Watanabe S, Kobayashi T, Nagatsu A, Sakakibara J, Okuyama H. Unusual effects of some vegetable oils on the survival time of stroke-prone spontaneously hypertensive rats. Lipids 1997; 32(7): 745–751.

    CAS  PubMed  Google Scholar 

  16. 16.

    Okuyama H, Yamada K, Miyazawa D, Yasui Y, Ohara N. Dietary lipids impacts on healthy ageing. Lipids 2007; 42(9): 821–825.

    CAS  PubMed  Google Scholar 

  17. 17.

    Lanzmann-Petithory D. Alpha-linolenic acid and cardiovascular diseases. J Nutr Health Aging 2001; 5(3): 179–183.

    CAS  PubMed  Google Scholar 

  18. 18.

    Vanschoonbeek K, de Maat MP, Heemskerk JW. Fish oil consumption and reduction of arterial disease. J Nutr 2003; 133(3): 657–660.

    CAS  PubMed  Google Scholar 

  19. 19.

    De Caterina R, Cybulsky MA, Clinton SK, Gimbrone MA Jr, Libby P. Omega-3 fatty acids and endothelial leukocyte adhesion molecules. Prostaglandins Leukot Essent Fatty Acids 1995; 52(2-3): 191–195.

    PubMed  Google Scholar 

  20. 20.

    Zhang L, Geng Y, Yin M, Mao L, Zhang S, Pan J. Low omega-6/omega-3 polyunsaturated fatty acid ratios reduce hepatic C-reactive protein expression in apolipoprotein E-null mice. Nutrition 2010; 26(7-8): 829–834.

    CAS  PubMed  Google Scholar 

  21. 21.

    Griffin MD, Sanders TA, Davies IG, Morgan LM, Millward DJ, Lewis F, Slaughter S, Cooper JA, Miller GJ, Griffin BA. Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity, lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45–70 y: the OPTILIP Study. Am J Clin Nutr 2006; 84(6): 1290–1298.

    CAS  PubMed  Google Scholar 

  22. 22.

    De Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, Guidollet J, Touboul P, Delaye J. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 1994; 343(8911): 1454–1459.

    PubMed  Google Scholar 

  23. 23.

    Jang JY, Kim TS, Cai J, Kim J, Kim Y, Shin K, Kim KS, Lee SP, Kang MH, Choi EK, Rhee MH, Kim YB. Perilla oil improves blood flow through inhibition of platelet aggregation and thrombus formation. Lab Anim Res 2014; 30(1): 21–27.

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Cai J, Jang JY, Kim J, Shin K, Kim KS, Park D, Kim TS, Lee SP, Ahn B, Choi EK, Lee J, Kim YB. Comparative effects of plant oils on the cerebral hemorrhage in stroke-prone spontaneously hypertensive rats. Nutr Neurosci 2016; 19(7): 318–326.

    CAS  PubMed  Google Scholar 

  25. 25.

    Heemskerk JW, Vossen RC, van Dam-Mieras MC. Polyunsaturated fatty acids and function of platelets and endothelial cells. Curr Opin Lipidol 1996; 7(1): 24–29.

    CAS  PubMed  Google Scholar 

  26. 26.

    Cheong SH, Kim MY, Sok DE, Hwang SY, Kim JH, Kim HR, Lee JH, Kim YB, Kim MR. Spirulina prevents atherosclerosis by reducing hypercholesterolemia in rabbits fed a high-cholesterol diet. J Nutr Sci Vitaminol (Tokyo) 2010; 56(1): 34–40.

    CAS  Google Scholar 

  27. 27.

    Park D, Kyung J, Kim D, Hwang S Y, Choi EK, Kim YB. Anti-hypercholesterolemic and anti-atherosclerotic effects of polarized-light therapy in rabbits fed a high-cholesterol diet. Lab Anim Res 2012; 28(1): 39–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Jang JY, Kim J, Cai J, Kim Y, Shin K, Kim TS, Lee SP, Park SK, Choi EK, Kim YB. An ethanolic extract of Angelica gigas improves atherosclerosis by inhibiting vascular smooth muscle cell proliferation. Lab Anim Res 2014; 30(2): 84–89.

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Kwon SC, Kim YB. Antioxidative and aldose reductase-inhibitory effects of a fermentation filtrate of Rubus coreanus. Lab Anim Res 2011; 27(4): 365–368.

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    McClelland GA, Stubbs RJ, Fix JA, Pogany SA, Zentner GM. Enhancement of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor efficacy through administration of a controlled-porosity osmotic pump dosage form. Pharm Res 1991; 8(7): 873–876.

    CAS  PubMed  Google Scholar 

  31. 31.

    Yim JE, Choue RW, Kim YS. Effects of dietary counceling and HMG-CoA reductase inhibitor treatment on serum lipid levels in hyperlipidemic patients. Kor Nutr Soc 1998; 8(1): 61–76.

    Google Scholar 

  32. 32.

    Blaha MJ, Bansal S, Rouf R, Golden SH, Blumenthal RS, Defilippis AP. A practical “ABCDE” approach to the metabolic syndrome. Mayo Clin Proc 2008; 83(3): 932–941.

    PubMed  Google Scholar 

  33. 33.

    Kurowska EM, Dresser GK, Deutsch L, Vachon D, Khalil W. Bioavailability of omega-3 essential fatty acids from perilla seed oil. Prostaglandins Leukot Essent Fatty Acids 2003; 68(3): 207–212.

    CAS  PubMed  Google Scholar 

  34. 34.

    Wei M, Xiong P, Zhang L, Fei M, Chen A, Li F. Perilla oil and exercise decrease expressions of tumor necrosis factor-alpha, plasminogen activator inhibitor-1 and highly sensitive C-reactive protein in patients with hyperlipidemia. J Tradit Chin Med 2013; 33(2): 170–175.

    PubMed  Google Scholar 

  35. 35.

    Eussen SR, Geleijnse JM, Giltay EJ, Rompelberg CJ, Klungel OH, Kromhout D. Effects of n-3 fatty acids on major cardiovascular events in statin users and non-users with a history of myocardial infarction. Eur Heart J 2012; 33(13): 1582–1588.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Holy EW, Forestier M, Richter EK, Akhmedov A, Leiber F, Camici GG, Mocharla P, Luscher TF, Beer JH, Tanner FC. Dietary α-linolenic acid inhibits arterial thrombus formation, tissue factor expression, and platelet activation. Arterioscler Thromb Vasc Biol 2011; 31(8): 1772–1780.

    CAS  PubMed  Google Scholar 

  37. 37.

    Ascherio A, Rimm EB, Giovannucci EL, Spiegelman D, Stampfer M, Willett WC. Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States. BMJ 1996; 313(7049): 84–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Hu FB, Stampfer MJ, Manson JE, Rimm EB, Wolk A, Colditz GA, Hennekens CH, Willett WC. Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr 1999; 69(5): 890–897.

    CAS  PubMed  Google Scholar 

  39. 39.

    Huang MZ, Naito Y, Watanabe S, Kobayashi T, Kanai H, Nagai H, Okuyama H. Effect of rapeseed and dietary oils on the mean survival time of stroke-prone spontaneously hypertensive rats. Biol Pharm Bull 1996; 19(4): 554–557.

    CAS  PubMed  Google Scholar 

  40. 40.

    Ratnayake S, Lewandowski P. Rapid bioassay-guided screening of toxic substances in vegetable oils that shorten the life of SHRSP rats. Lipids Health Dis 2010; 9: 13.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Shimizu T, Igarashi J, Ohtuka Y, Oguchi S, Kaneko K, Yamashiro Y. Effects of n-3 polyunsaturated fatty acids and vitamin E on colonic mucosal leukotriene generation, lipid peroxidation, and microcirculation in rats with experimental colitis. Digestion 2001; 63(1): 49–54.

    CAS  PubMed  Google Scholar 

  42. 42.

    Zhao G, Zang SY, Jiang ZH, Chen YY, Ji XH, Lu BF, Wu JH, Qin GW, Guo LH. Postischemic administration of liposome-encapsulated luteolin prevents against ischemia-reperfusion injury in a rat middle cerebral artery occlusion model. J Nutr Biochem 2011; 22(10): 929–936.

    CAS  PubMed  Google Scholar 

  43. 43.

    Pan CH, Tsai CH, Lin WH, Chen GY, Wu CH. Ethanolic Extract of Vitis thunbergii Exhibits Lipid Lowering Properties via Modulation of the AMPK-ACC Pathway in Hypercholesterolemic Rabbits. Evid Based Complement Alternat Med 2012; 2012: 436786.

    PubMed  PubMed Central  Google Scholar 

  44. 44.

    Sylvester KW, Cheng JW, Mehra MR. Esomeprazole and aspirin fixed combination for the prevention of cardiovascular events. Vasc Health Risk Manag 2013; 9: 245–254.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Fintel DJ. Oral antiplatelet therapy for atherothrombotic disease: overview of current and emerging treatment options. Vasc Health Risk Manag 2012; 8: 77–89.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by “Food Functionality Evaluation program” under the Ministry of Agriculture, Food and Rural Affairs and partly Korea Food Research Institute (G2015).

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Ehn-Kyoung Choi or Yun-Bae Kim.

Rights and permissions

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cha, Y., Jang, J.Y., Ban, Y. et al. Anti-atherosclerotic effects of perilla oil in rabbits fed a high-cholesterol diet. Lab Anim Res 32, 171–179 (2016). https://doi.org/10.5625/lar.2016.32.3.171

Download citation

Keywords

  • Hypercholesterolemia
  • atherosclerosis
  • fatty liver
  • lipid peroxidation
  • perilla oil