Journal Mobile Options
Table of Contents
Vol. 45, No. 5, 2001
Issue release date: September–October 2001

Effect of Naringin Supplementation on Cholesterol Metabolism and Antioxidant Status in Rats Fed High Cholesterol with Different Levels of Vitamin E

Choi M.-S. · Do K.-M. · Park Y.S. · Jeon S.-M. · Jeong T.-S. · Lee Y.-K. · Lee M.-K. · Bok S.-H.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Some bioflavonoids are potent antioxidants and have pharmacological effects similar to those of vitamin E. The interactive effect of naringin and vitamin E was studied with respect to cholesterol metabolism and antioxidant status. Naringin supplementation (0.1%, wt/wt) with comparable levels of vitamin E was given to rats with a high-cholesterol (1%, wt/wt) diet for 5 weeks. The amount of vitamin E included in naringin-free and naringin diets was a low (low-E) and a normal (normal-E) level. The naringin supplementation significantly lowered the concentrations of plasma cholesterol and triglyceride compared to the naringin-free group in low vitamin E-fed rats. HMG-CoA reductase activity was significantly lowered by naringin supplementation within both the low-vitamin E group (794.64 ± 9.87 vs. 432.18 ± 12.33 pmol/min/mg protein, mean ± SE; p < 0.05) and normal-vitamin E group (358.82 ± 11.4 vs. 218.22 ± 9.47 pmol/min/mg protein, mean ± SE; p < 0.05) compared to each of the naringin-free group. The HMG-CoA reductase activity was also significantly lowered by increased dietary vitamin E when compared within the naringin and naringin-free group, respectively. Neither dietary naringin nor vitamin E did significantly change the activities of hepatic antioxidant enzymes and plasma thiobarbituric acid-reactive substance level. These data indicate that naringin lowers the plasma lipid concentrations when the dietary vitamin E level is low. The HMG-CoA reductase-inhibitory effect of naringin was more potent when dietary vitamin E was at a normal level. These data may contribute to understanding the interactive effect of naringin and vitamin E on cholesterol biosynthesis in high-cholesterol-fed rats.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Havsteen B: Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 1983;32:1141–1148.
  2. Bors W, Heller W, Michel C, Saran N: Flavonoids as antioxidants: Determination of radical-scavenging efficiencies. Methods Enzymol 1990;186:343–355.
  3. Di PT, Auteri A: Action of S5682 on the complement system. In vitro and in vivo study. Int Angiol 1988;7:11–15.
  4. Tang BY, Adams NR: Effect of equol on estrogen receptors and on synthesis of DNA and protein in the immature rat uterus. J Endocrinol 1980;85:291–297.
  5. Nishino H, Nagao M, Fujiki H, Sugimura T: Role of flavonoids in suppressing the enhancement of phospholipid metabolism by tumor promoters. Cancer Lett 1983;21:1–8.

    External Resources

  6. Chan AC: Vitamin E and atherosclerosis. J Nutr 1998;128:1593–1596.
  7. Sharma N, Desigan B, Ghosh S, Sanyal SN, Ganguly NK, Majumdar S: Effect of antioxidant vitamin E as a protective factor in experimental atherosclerosis in rhesus monkeys. Ann Nutr Metab 1999;43:181–190.
  8. Aboobaker VS, Balgi AD, Bhattacharya RK: In vivo effect of dietary factors on the molecular action of aflatoxin B1: Role of non-nutrient phenolic compounds on the catalytic activity of liver fraction. In Vivo 1994;8:1095–1098.

    External Resources

  9. Lambev I, Krushkov I, Zheliazkov D, Nikolov N: Antiexudative effect of naringin in experimental pulmonary edema and peritonitis. Eksp Med Morfol 1980;19:207–212.

    External Resources

  10. Fisher KD: Evaluation of the health aspects of hesperidin, naringin, and citrus bioflavonoid extract as food ingredients. Washington, Bureau of Food and Drug Administration, Department of Health and Human Services, Contract No FDA, 1982, 223-78-2100.
  11. Monforte MT, Trovato A, Kirjavainen S, Forestieri AM, Galati, EM, LoCurto RB: Biological effects of hesperidin, a citrus flavonoid (note II): Hypolipidemic activity on experimental hypercholesterolemia in rats. Farmaco 1995;50:595–599.
  12. Kawaguchi K, Mizuno T, Aida K, Uchino K: Hesperidin as an inhibitor of lipases from porcine pancreas and Pseudomonas. Biosci Biotechnol Biochem 1997;61:102–104.

    External Resources

  13. Bocan TM, Mueller SB, Brown EQ, Lee P, Bocan MJ, Rea T, Pape ME: HMG-CoA reductase and ACAT inhibitors act synergistically to lower plasma cholesterol and limit atherosclerotic lesion in the cholesterol-fed rabbit. Atherosclerosis 1998;139:21–30.

    External Resources

  14. Hay JM, Yu WM, Ashraf T: Pharmacoeconomics of lipid-lowering agents for primary and secondary prevention of coronary artery disease. Pharmacoeconomics 1999;15:47–74.
  15. American Institute of Nutrition: Report of the American Institute of Nutrition. Ad Hoc Committee on Standards for Nutritional Studies. J Nutr 1977;107:1340–1348.
  16. American Institute of Nutrition: Report of Ad Hoc Committee on Standards for Nutritional Studies. J Nutr 1980;110:1717–1726.
  17. National Research Council: Nutrient Requirements of Laboratory Animals, ed 4. Washington, National Academy Press, 1995, pp 11–79.
  18. Allain CC, Poon LS, Chan CSG: Enzymatic determination of total serum cholesterol. Clin Chem 1974;20:470–475.
  19. Waenic RG, Albers JJ: A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating a high density lipoprotein cholesterol. J Lipid Res 1978;19:65–76.
  20. McGowan MW, Artiss JD, Strandbergh DR, Zak B: A peroxidase-coupled method for the colorimetric determination of serum triglycerides. Clin Chem 1983;29:538–542.
  21. Folch J, Lees M, Sloan-Stanley GH: A simple method for isolation and purification of total lipids from animal tissues. J Biol Chem 1957;226:497–509.
  22. Hulcher FH, Oleson WH: Simplified spectrophotometric assay for microsomal 3-hydroxy-3-methylglutaryl CoA reductase by measurement of coenzyme A. J Lipid Res 1973;14:625–631.
  23. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–254.
  24. Shapiro DJ, Nordstrom JL, Mitschelen JJ, Rodwell VW, Schimke RT: Microassay for 3-hydroxy-3-methylglutaryl-CoA reductase in rat liver and in L-cell fibroblasts. Biochim Biophys Acta 1974;370:369–377.
  25. Erickson SK, Schrewsbery MA, Brooks C, Meyer DJ: Rat liver acyl-coenzyme A:cholesterol acyltransferase: Its regulation in vivo and some of properties in vitro. J Lipid Res 1980;21:930–941.
  26. Gillies PJ, Rathgeb KA, Robinson CS: Regulation of acyl-CoA:cholesterol acyltransferase activity in normal and atherosclerotic rabbit aortas: Role of a cholesterol substrate pool. Exp Mol Pathol 1986;44:320–339.
  27. Czubayko F, Beumers B, Lutjohann D, von Bergmann K: A simplified micro-method for quantification of fecal excretion of neutral and acidic sterols for outpatient studies in humans. J Lipid Res 1992;32:1861–1867.
  28. Michael JC, Ian AM: Enzymic determination of 3α-, 7α-, and 12α-hydroxyl groups of fecal bile salts. Clin Chem 1980;26:1298–1300.
  29. Bieri G, Tolliver JJ, Catignani GL: Simultaneous determination of alpha-tocopherol and retinol in plasma or red blood cells by high pressure liquid chromatograph. Am J Clin Nutr 1979;32:2143–2149.
  30. Marklund S, Marklund G: Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47:469–474.
  31. Aebi H: Catalase; in Method of Enzymatic Analysis. New York, Academic Press, 1974, vol 2, pp 673–684.
  32. Paglia ED, Valentine WN: Studies on the quantitative and qualitative characterization of erythrocytes glutathione peroxidase. J Lab Clin Med 1967;70:158–169.
  33. Tarladgis BG, Pearson AM, Dugan LR: Chemistry of the 2-thiobarbituric acid test for determination of oxidative rancidity in foods. J Sci Food Agric 1964;15:602–607.
  34. Kroyer G: The antioxidant activity of citrus fruit peels. Z Ernährungswiss 1986;25:63–69.

    External Resources

  35. Bjorkhem I: Mechanism of bile acid biosynthesis in mammalian liver; in Danielsson H, Sjovall J (eds): New Comprehensive Biochemistry. Amsterdam, Elsevier Scientific, 1985, pp 231–278.
  36. Ammer B, Weintraub RA, Johnson JV, Yost RA, Rouseff RL: Flavanone absorption after naringin, hesperidin, and citrus administration. Clin Pharmacol Ther 1996;60:34–40.
  37. Lee SH, Park YB, Bae KH, Bok SH, Kwon YK, Lee ES, Choi MS: Cholesterol-lowering activity of naringenin via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase in rats. Ann Nutr Metab 1999;43:173–180.
  38. Shin YW, Bok SH, Jeong TS, Bae KH, Jeong NH, Choi MS, Lee SH, Park YB: Hypocholesterolemic effect of naringin is associated with hepatic cholesterol regulating enzyme changes. Int J Vitam Nutr Res 1999;69:341–347.
  39. 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 acyltransferase are lower in rats fed citrus peel extract or a mixture of citrus bioflavonoids. J Nutr 1999;129:1182–1185.
  40. Kurowska EM, Borradaile NM, Spence JD, Carroll KK: Hypocholesterolemic effects of dietary citrus juices in rabbits. Nutr Res 2000;20:121–129.
  41. Masugi F, Nakamura T: Effect of vitamin E deficiency on the level of superoxide dismutase, glutathione peroxidase, catalase and lipid peroxide in rat liver. Int J Vitam Nutr Res 1976;46:187–191.
  42. Chen L, Haught WH, Yang B, Saldeen TG, Parathasarathy S, Mehta JL: Preservation of endogenous antioxidant activity and inhibition of lipid peroxidation as common mechanisms of antiatherosclerotic effects of vitamin E, lovastatin and amlodipine. J Am Coll Cardiol 1997;30:569–575.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50