Skip to main content
Log in

Evaluation of the anti-atherogenic potential of chrysin in Wistar rats

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Hypercholesterolemia is one of the major risk factors that precipitate coronary heart disease and atherosclerosis. Oxidative stress is believed to contribute to the pathogenesis of hypercholesterolemic atherosclerosis; hence, various antioxidant compounds are being evaluated for potential anti-atherogenic effects. In the present study, the putative anti-atherogenic and antioxidant efficacy of a flavonoid, chrysin, was evaluated in an experimental model of atherosclerosis. In male, albino Wistar rats fed an atherogenic diet for 45 days and treated with saline, significantly higher mean levels of serum lipid profile parameters (total cholesterol, triglycerides, low-density, and very low-density lipoprotein cholesterol), lower mean levels of high-density lipoprotein cholesterol and higher mean serum levels of hepatic marker enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase) were observed when compared with the levels in rats fed a control diet. In addition, significantly lower mean hepatic levels of lipoprotein lipase, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) and non-enzymatic antioxidants (reduced glutathione, and vitamins C and E), and a significantly higher mean level of hepatic malondialdehyde (MDA) were noted in comparison to the values in control rats. In atherogenic diet-fed rats that received chrysin orally (200 mg/kg b.wt) for 15 days, starting 30 days after the start of the atherogenic diet, significantly lower mean serum levels of lipid profile parameters (except for HDL-cholesterol which was elevated), hepatic marker enzymes, and significantly higher mean hepatic levels of LPL, HMG-CoA reductase, enzymatic, and non-enzymatic antioxidants and significantly lower mean levels of hepatic MDA were noted, compared to the values in atherogenic diet-fed, saline-treated rats. Histopathological studies appeared to suggest the protective effect of chrysin on the hepatic tissue and aorta of atherosclerotic rats. These results suggest that chrysin has anti-atherogenic potential in an experimental setting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Mensink RP, Aro A, Den Hond E, German JB, Griffin BA, ten Meer HU, Mutanen M, Pannemans D, Stahl W (2003) PASSCLAIM - Diet-related cardiovascular disease. Eur J Nutr 42:16–27

    Article  Google Scholar 

  2. Goldstein JL, Brown MS (1990) Regulation of the mevalonate pathway. Nature 343:425–430

    Article  CAS  PubMed  Google Scholar 

  3. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320:915–924

    Article  CAS  PubMed  Google Scholar 

  4. Halliwell B (1996) Mechanisms involved in the generation of free radicals. Pathol Biol (Paris) 44:6–13

    CAS  Google Scholar 

  5. Shi W, Haberland ME, Jien ML, Shih DM, Lusis AJ (2000) Endothelial responses to oxidized lipoproteins determine genetic susceptibility to atherosclerosis in mice. Circulation 102:75–81

    Article  CAS  PubMed  Google Scholar 

  6. Parthasarathy S, Santanam N, Ramachandran S, Meilhac O (2000) Potential role of oxidized lipids and lipoproteins in antioxidant defense. Free Radic Res 33:197–215

    Article  CAS  PubMed  Google Scholar 

  7. Carew TE, Schwenke DC, Steinberg D (1987) Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci USA 84:7725–7729

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P (1995) The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med 332:488–493

    Article  CAS  PubMed  Google Scholar 

  9. Diaz MN, Frei B, Vita JA, Keaney JF Jr (1997) Antioxidants and atherosclerotic heart disease. N Engl J Med 337:408–416

    Article  CAS  PubMed  Google Scholar 

  10. Chrysselis MC, Rekka EA, Kourounakis PN (2000) Hypocholesterolemic and hypolipidemic activity of some novel morpholine derivatives with antioxidant activity. J Med Chem 43:609–612

    Article  CAS  PubMed  Google Scholar 

  11. Wolfman C, Viola H, Paladini A, Dajas F, Medina JH (1994) Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacol Biochem Behav 47:1–4

    Article  CAS  Google Scholar 

  12. Rapta P, Misík V, Stasko A, Vrábel I (1995) Redox intermediates of flavonoids and caffeic acid esters from propolis: an EPR spectroscopy and cyclic voltammetry study. Free Radic Biol Med 18:901–908

    Article  CAS  PubMed  Google Scholar 

  13. Williams CA, Harborne JB, Newman M, Greenham J, Eagles J (1997) Chrysin and other leaf exudate flavonoids in the genus Pelargonium. Phytochemistry 46:1349–1353

    Article  CAS  PubMed  Google Scholar 

  14. Habtemariam S (1997) Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-alpha in L-929 tumor cells. J Nat Prod 60:775–778

    Article  CAS  PubMed  Google Scholar 

  15. Dhawan K, Kumar S, Sharma A (2002) Beneficial effects of chrysin and benzoflavone on virility in 2-year-old male rats. J Med Food 5:43–48

    Article  CAS  PubMed  Google Scholar 

  16. Cho H, Yun CW, Park WK, Kong JY, Kim KS, Park Y, Lee S, Kim BK (2004) Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives. Pharmacol Res 49:37–43

    Article  CAS  PubMed  Google Scholar 

  17. Bradford M (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  18. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    CAS  PubMed  Google Scholar 

  19. Baginsky ML (1981) Measurement of lipoprotein lipase and hepatic triglyceride lipase in human postheparin plasma. Methods Enzymol 72:325–338

    Article  CAS  Google Scholar 

  20. Rao AV, Ramakrishnan S (1975) Indirect assessment of hydroxymethylglutaryl-CoA reductase (NADPH) activity in liver tissue. Clin Chem 21:1523–1525

    CAS  PubMed  Google Scholar 

  21. King J (1965) The transferases-alanine and aspartate transaminases. In: Van D (ed) Practical clinical enzymology. Nostrand Company Limited, London, pp 121–138

    Google Scholar 

  22. King J (1965) The hydrolases—acid and alkaline phosphatases. In: Van D (ed) Practical clinical enzymology. Nostrand Company Limited, London, pp 191–208

    Google Scholar 

  23. King J (1965) The dehydrogenases or oxidoreductases—lactate dehydrogenase. In: Van D (ed) Practical clinical enzymology. Nostrand Company Limited, London, pp 83–93

    Google Scholar 

  24. Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394

    Article  CAS  PubMed  Google Scholar 

  25. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  CAS  PubMed  Google Scholar 

  26. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590

    Article  CAS  Google Scholar 

  27. Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochim Biophys Acta 582:67–78

    Article  CAS  PubMed  Google Scholar 

  28. Omaye ST, Turnbull JD, Sauberlich HE (1979) Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol 62:3–11

    Article  CAS  PubMed  Google Scholar 

  29. Desai ID (1984) Vitamin E analysis methods for animal tissues. Methods Enzymol 105:138–147

    Article  CAS  Google Scholar 

  30. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  31. Drury RAD, Wallington EA (1980) Carleton’s histological technique. Oxford University Press, New York

    Google Scholar 

  32. Eisenberg DA (1998) Cholesterol lowering in the management of coronary artery disease: the clinical implications of recent trials. Am J Med 104:2S–5S

    Article  CAS  PubMed  Google Scholar 

  33. Sudhahar V, Kumar SA, Varalakshmi P (2006) Role of lupeol and lupeol linoleate on lipemic-oxidative stress in experimental hypercholesterolemia. Life Sci 78:1329–1335

    Article  CAS  PubMed  Google Scholar 

  34. Thiruchenduran M, Vijayan NA, Sawaminathan JK, Devaraj SN (2011) Protective effect of grape seed proanthocyanidins against cholesterol cholic acid diet-induced hypercholesterolemia in rats. Cardiovasc Pathol 20:361–368. doi:10.1016/j.carpath.2010.09.002

    Article  CAS  PubMed  Google Scholar 

  35. Hirunpanich V, Utaipat A, Morales NP, Bunyapraphatsara N, Sato H, Herunsale A, Suthisisang C (2006) Hypocholesterolemic and antioxidant effects of aqueous extracts from the dried calyx of Hibiscus sabdariffa L. in hypercholesterolemic rats. J Ethnopharmacol 103:252–260

    Article  PubMed  Google Scholar 

  36. Wang L, Geng C, Jiang L, Gong D, Liu D, Yoshimura H, Zhong L (2008) The anti-atherosclerotic effect of olive leaf extract is related to suppressed inflammatory response in rabbits with experimental atherosclerosis. Eur J Nutr 47:235–243. doi:10.1007/s00394-008-0717-8

    Article  PubMed  Google Scholar 

  37. Raja B, Saravanakumar M, Sathya G (2012) Veratric acid ameliorates hyperlipidemia and oxidative stress in Wistar rats fed an atherogenic diet. Mol Cell Biochem 366:21–30. doi:10.1007/s11010-012-1278-y

    Article  CAS  PubMed  Google Scholar 

  38. Balasinska B (1998) Hypocholesterolemic effect of dietary evening primrose (Oenothera paradoxa) cake extract in rats. Food Chem 63:453–459

    Article  CAS  Google Scholar 

  39. Chanet A, Milenkovic D, Deval C, Potier M, Constans J, Mazur A, Bennetau-Pelissero C, Morand C, Bérard AM (2012) Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice. J Nutr Biochem 23:469–477. doi:10.1016/j.jnutbio.2011.02.001

    Article  CAS  PubMed  Google Scholar 

  40. Kim HK, Jeong TS, Lee MK, Park YB, Choi MS (2003) Lipid-lowering efficacy of hesperetin metabolites in high-cholesterol fed rats. Clin Chim Acta 327:129–137

    Article  CAS  PubMed  Google Scholar 

  41. Bensadoun A (1991) Lipoprotein lipase. Annu Rev Nutr 11:217–237

    Article  CAS  PubMed  Google Scholar 

  42. Reymer PW, Groenemeyer BE, Gagné E, Miao L, Appelman EE, Seidel JC, Kromhout D, Bijvoet SM, van de Oever K, Bruin T et al (1995) A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) contributes to the expression of familial combined hyperlipidemia. Hum Mol Genet 4:1543–1549

    Article  CAS  PubMed  Google Scholar 

  43. Kavitha R, Nalini N (2001) Hypolipidemic effect of green and red chilli extract in rats fed high fat diet. Med Sci Res 28:17–21

    Google Scholar 

  44. Sudhahar V, Ashokkumar S, Varalakshmi P (2006) Effect of lupeol and lupeol linoleate on lipemic-hepatocellular aberrations in rats fed a high cholesterol diet. Mol Nutr Food Res 50:1212–1219

    Article  CAS  PubMed  Google Scholar 

  45. Kita T, Brown MS, Goldstein JL (1980) Feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in livers of mice treated with mevinolin, a competitive inhibitor of the reductase. J Clin Invest 66:1094–1100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Vijayakumar RS, Nalini N (2006) Lipid-lowering efficacy of piperine from Piper nigrum L. in high-fat diet and antithyroid drug-induced hypercholesterolemic rats. J Food Biochem 30:405–421

    Article  CAS  Google Scholar 

  47. Napoli C, de Nigris F, Palinski W (2001) Multiple role of reactive oxygen species in the arterial wall. J Cell Biochem 82:674–682

    Article  CAS  PubMed  Google Scholar 

  48. Keaney JF Jr, Gaziano JM, Xu A, Frei B, Curran-Celentano J, Shwaery GT, Loscalzo J, Vita JA (1994) Low-dose alpha-tocopherol improves and high-dose alpha-tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits. J Clin Invest 93:844–851

    Article  PubMed Central  PubMed  Google Scholar 

  49. Gupta PP, Tandon HD, Ramalingaswami V (1976) Cirrhosis of the liver in rabbits induced by a high cholesterol diet—an experimental model. Indian J Med Res 64:1516–1526

    CAS  PubMed  Google Scholar 

  50. Molander DW, Wroblewski F, Ladue JS (1955) Serum glutamic oxalacetic transaminase as an index of hepatocellular integrity. J Lab Clin Med 46:831–839

    CAS  PubMed  Google Scholar 

  51. Prasad K, Kalra J (1993) Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E. Am Heart J 125:958–973

    Article  CAS  PubMed  Google Scholar 

  52. Sheela CG, Augusti KT (1995) Antiperoxide effects of S-allyl cysteine sulphoxide isolated from Allium sativum Linn and gugulipid in cholesterol diet fed rats. Indian J Exp Biol 33:337–341

    CAS  PubMed  Google Scholar 

  53. Sathiavelu J, Senapathy GJ, Devaraj R, Namasivayam N (2009) Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats. J Pharm Pharmacol 61:809–817

    Article  CAS  PubMed  Google Scholar 

  54. Recknagel RO, Glende EA Jr, Britton RS (1991) Free radical damage and lipid peroxidation. In: Meeks RG (ed) Hepatotoxicology. CRC Press, Boca Raton, pp 401–436

    Google Scholar 

  55. Deepa PR, Varalakshmi P (2004) Protective effects of certoparin sodium, a low molecular weight heparin derivative, in experimental atherosclerosis. Clin Chim Acta 339:105–115

    Article  CAS  PubMed  Google Scholar 

  56. Traber MG, Sies H (1996) Vitamin E in humans: demand and delivery. Annu Rev Nutr 16:321–347

    Article  CAS  PubMed  Google Scholar 

  57. Freeman BA, Crapo JD (1982) Biology of disease: free radicals and tissue injury. Lab Invest 47:412–426

    CAS  Google Scholar 

  58. Halliwell B (2000) Lipid peroxidation, antioxidants and cardiovascular disease: how should we move forward? Cardiovasc Res 47:410–418

    Article  CAS  PubMed  Google Scholar 

  59. Gutteridge JM, Halliwell B (1990) The measurement and mechanism of lipid peroxidation in biological systems. Trends Biochem Sci 15:129–135

    Article  CAS  PubMed  Google Scholar 

  60. Geetha RK, Vasudevan DM (2004) Inhibition of lipid peroxidation by botanical extracts of Ocimum sanctum: in vivo and in vitro studies. Life Sci 76:21–28

    Article  CAS  PubMed  Google Scholar 

  61. Wissler RW (1992) Theories and new horizons in the pathogenesis of atherosclerosis and the mechanisms of clinical effects. Arch Pathol Lab Med 116:1281–1291

    CAS  PubMed  Google Scholar 

  62. Gökkusu C, Ademoğlu E, Türkoğlu UM, Oz H, Oz F (1996) Thymosin alpha 1 protects liver and aorta from oxidative damage in atherosclerotic rabbits. Life Sci 59:1059–1067

    Article  PubMed  Google Scholar 

  63. Sankhari JM, Thounaojam MC, Jadeja RN, Devkar RV, Ramachandran AV (2012) Anthocyanin-rich red cabbage (Brassica oleracea L.) extract attenuates cardiac and hepatic oxidative stress in rats fed an atherogenic diet. J Sci Food Agric 92:1688–1693

    Article  CAS  PubMed  Google Scholar 

  64. Mitani H, Egashira K, Kimura M (2003) HMG-CoA reductase inhibitor, fluvastatin, has cholesterol-lowering independent “direct” effects on atherosclerotic vessels in high cholesterol diet-fed rabbits. Pharmacol Res 48:417–427

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Financial assistance provided by the Department of Science and Technology-Promotion of University Research and Scientific Excellence (DST-PURSE) to the first author is gratefully acknowledged. Financial assistance provided by University Grants Commission-Basic Scientific Research (UGC-BSR) in the form of one time grant to the corresponding author is gratefully acknowledged. The instrumentation facility provided by the University Grant Commission-Special Assistance Programme (UGC-SAP) of the Department of Animal Science, Bharathidasan University, is acknowledged.

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pitchairaj Geraldine.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anandhi, R., Thomas, P.A. & Geraldine, P. Evaluation of the anti-atherogenic potential of chrysin in Wistar rats. Mol Cell Biochem 385, 103–113 (2014). https://doi.org/10.1007/s11010-013-1819-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1819-z

Keywords

Navigation