Skip to main content
SpringerLink
Log in

Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacin-bound chromium in a hamster atherosclerosis model

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

Abstract

Atherosclerosis is a disease of the arteries in which fatty plaques develop on the inner arterial wall, which eventually obstructs blood flow. Identified risk factors for atherosclerosis include genetics, diet, lifestyle, smoking, circulating lipid and cholesterol levels, and molecular and circulating signals of chronic vascular inflammation. The link between flavonoids and atherosclerosis is based partly on the evidence that some flavonoids possess antioxidant properties and have been shown to be potent inhibitors of LDL oxidation in vitro. Hypercholesterolemia, a significant cardiovascular risk factor is prevalent in the American population. Grape seed proanthocyanidin extracts are known to exhibit a broad spectrum of chemopreventive and cardioprotective properties against oxidative stress. A recent study has shown that a combination of IH636 grape seed proanthocyanidin extract (GSPE) and a niacin-bound chromium (NBC) can decrease total cholesterol, LDL and oxidized LDL levels in hypercholesterolemic human subjects. In this study, we assessed the efficacy of GSPE supplementation in hamsters, singly and in combination with NBC, since these animals have a similar lipid profile to hypercholesterolemic humans when fed a hypercholesterolemic diet of 0.2% cholesterol and 10% coconut oil (HCD). After 10 weeks of feeding HCD, these animals developed foam cells, which is a biomarker of early stages of atherosclerosis. Atherosclerosis (% of aorta covered with foam cells) was reduced by approximately 50% and 63% following supplementation of these animals with 50 mg/kg and 100 mg/kg of GSPE, respectively, in conjunction with a HCD, while approximately 32% reduction was observed following supplementation of GSPE plus NBC. A minimum of 7–9 animals were used in each study group. GSPE alone and in combination with NBC exerted a pronounced effect on the cholesterol, and triglyceride levels, as well as oxidative lipid damage as demonstrated by the formation of thiobarbituric acid reactive substances (TBARS). This data demonstrates that GSPE and NBC may provide significant health benefits by dramatically ameliorating the incidence of atherosclerosis as demonstrated by reducing the formation of foam cells.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Martinet W, Knaapen MW, De Meyer GR, Herman AG, Kockx MM: Oxidative DNA damage and repair in experimental atherosclerosis are reversed by dietary lipid lowering. Circ Res 88: 648-650, 2001

    Google Scholar 

  2. Chen Z, Ishibashi S, Perrey S, Osuga J, Gotoda T, Kitamine T, Tamura Y, Okazaki H, Yahagi N, Iizuka Y, Shionoiri F, Ohashi K, Harada K, Shimono H, Nagai R, Yamada N: Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: Pleiotropic effects on CD36 expression and HDL. Arteriosclerosis Thromb Vasc Biol 21: 372-377, 2001

    Google Scholar 

  3. Zingg JM, Ricciarelli R, Azzi A: Scavenger receptor regulation and atherosclerosis. Biofactors 11: 189-200, 2000

    Google Scholar 

  4. Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, Joshi SS, Preuss HG: Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology 148: 187-197, 2000

    Google Scholar 

  5. Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ: Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol 93: 179-189, 1997

    Google Scholar 

  6. Sato M, Maulik G, Ray PS, Bagchi D, Das DK: Cardioprotective effects of grape seed proanthocyanidin against ischemic reperfusion injury. J Mol Cell Cardiol 31: 1289-1297, 1999

    Google Scholar 

  7. Ray SD, Patel D, Wong V, Bagchi D: In vivo protection of DNA damage associated apoptotic and necrotic cell deaths during acetaminophen induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract. Res Commun Mol Path Pharmacol 107: 137-166, 2000

    Google Scholar 

  8. Preuss HG, Wallerstedt D, Talpur N, Tutuncuoglu SO, Echard B, Myers A, Bui M, Bagchi D: Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: A pilot study. J Med 31: 227-246, 2000

    Google Scholar 

  9. Ray S, Bagchi D, Lim PM, Bagchi M, Gross SM, Kothari SC, Preuss HG, Stohs SJ: Acute and long-term safety evaluation of a novel IH636 grape seed proanthocyanidin extract. Res Commun Mol Pathol Pharmacol 109: 165-197, 2001

    Google Scholar 

  10. Wren AF, Cleary M, Frantz C, Melton S, Norris L: 90-Day oral toxicity study of a grape seed extract (IH636) in rats. J Agric Food Chem 27: 2180-2192, 2002

    Google Scholar 

  11. Preuss HG, Anderson RA: Chromium update: Examining recent literature 1997-1998. Curr Opin Clin Nutr Met Care 6: 509-512, 1998

    Google Scholar 

  12. Abernathy CO, Cantilli R, Du JT: Essentiality versus toxicity: Some considerations in the risk assessment of essential trace elements. In: J. Saxena (ed). Hazard Assessment of Chemicals 8. Taylor and Francis, Washington, DC, 1993, pp 81-113

    Google Scholar 

  13. Foxall TL, Shwaery GT, Stucchi AF, Nicolosi RJ, Wong SS: Dose-related effects of doxazosin on plasma lipids and aortic fatty streak formation in the hypercholersterolemic hamster model. Am J Pathol 140: 1357-1363, 1992

    Google Scholar 

  14. Kowala MC, Nunnari JJ, Durham SK, Nicolosi RJ: Doxazosin and cholestyramine similarly decrease fatty streak formation in the aortic arch of hyperlipidemic hamsters. Atherosclerosis 91: 35-49, 1991

    Google Scholar 

  15. Lepage G, Munoz G, Champagne J, Roy CC: Preparative steps necessary for the accurate measurement of malondialdehyde by high-performance liquid chromatography. Anal Biochem 197: 277-283, 1991

    Google Scholar 

  16. Gaspardone A, Crea F, Iamele M, Tomai F, Versaci F, Borioni R, Chiariello L, Gioffre PA: Risk factors in patients with different clinical and angiographic manifestations of ischemic heart disease. Cardiologia 40: 679-684, 1995

    Google Scholar 

  17. Lichenstein AH: Atherosclerosis in present knowledge in nutrition 7: 430-437, 1996

    Google Scholar 

  18. Bui MN, Sack, MN, Moutsatsos G, Lu DY, Katz P, McCown R, Breall JA, Rackley CE: Autoantibody titers to oxidized low-density lipoprotein in patients with coronary atherosclerosis. Am Heart J 131: 663-667, 1996

    Google Scholar 

  19. Sato M, Bagchi D, Tosaki A, Das DK: Grape seed proanthocyanidin reduces cardiomyocyte apoptosis by inhibiting ischemia/reperfusion-induced activation of JNK-1 and C-JUN. Free Rad Biol Med 31: 729-737, 2001

    Google Scholar 

  20. Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J, Stohs SJ: Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. Gen Pharmacol 30: 771-776, 1998

    Google Scholar 

  21. Bagchi M, Balmoori J, Bagchi D, Ray SD, Kuszynski C, Stohs SJ: Smokeless tobacco, oxidative stress, apoptosis, and antioxidants in human oral keratinocytes. Free Rad Biol Med 26: 992-1000, 1999

    Google Scholar 

  22. Bagchi D, Ray SD, Patel D, Bagchi M: Protection against drug-and chemical-induced multiorgan toxicity by a novel IH636 grape seed proanthocyanidin extract. Drugs Exper Clin Res XXVII: 3-15, 2001

    Google Scholar 

  23. Mertz W: Chromium in human nutrition: A review. J Nutr 123: 626-633, 1993

    Google Scholar 

  24. Olin KL, Stearns DM, Armstrong WH, Keen CL: Comparative retention/ absorbtion of 51chromium (51Cr) from 51Cr chloride, 51Cr nicotinate and 51Cr picolinate in a rat model. Trace Elem Electro 11: 182-186, 1994

    Google Scholar 

  25. Preuss HG, Grojec PL, Lieberman S, Anderson RA: Effects of different chromium compounds on blood pressure and lipid peroxidation in spontaneously hypertensive rats. Clin Nephrol 47: 325-330, 1997

    Google Scholar 

  26. Preuss HG, Gondal JA, Bustos E, Bushehri N, Lieberman S, Bryden NA, Polansky MM, Anderson RA: Effects of chromium and guar on sugar-induced hypertension in rats. Clin Nephr 44: 170-177, 1995

    Google Scholar 

  27. Lefavi RG, Wilson GD, Keith RE, Anderson RA, Blessing DL, Hames CG, McMillan JL: Lipid-lowering effects of a dietary chromium (III)-nicotinic acid complex in male athletes. Nutr Res 13: 239-249, 1993

    Google Scholar 

  28. Grant KE, Chandler RM, Castle AL, Ivy JL: Chromium and exercise training: Effect on obese women. Med Sci Sports Exerc 29: 992-998, 1997

    Google Scholar 

  29. Crawford V, Scheckenbach R, Preuss HG: Effects of niacin-bound chromium supplementation on body composition in overweight African-American women. Diabetes Obes Metab 1: 331-337, 1999

    Google Scholar 

  30. Preuss HG, Bagchi D, Bagchi M: Protective effects of a novel grape seed proanthocyanidin extract and niacin-bound chromium on advancing age and various aspects of syndrome X. In: D.K. Das, F. Ursini (eds). Alcohol and Wine in Health and Disease. Annals of the New York Academy of Sciences (in press)

  31. Preuss HG, Montamarry S, Echard B, Scheckenbach R, Bagchi D: Long-term effects of chromium, grape seed extract and zinc on various metabolic parameters of rats. Mol Cell Biochem 235: 95-102, 2001

    Google Scholar 

  32. Tavintharan S, Kashyap ML: The benefits of niacin in atherosclerosis. Curr Atherosclerosis Rep 3: 74-82, 2001

    Google Scholar 

  33. Athyros VG, Papageorgiou AA, Demitriadis DS, Kontopoulos AG: Atorvastatin plus pravastatin for the treatment of heterozygous familial hypercholesterolaemia - a pilot study. Curr Med Res Opin 17: 267-272, 2001

    Google Scholar 

  34. Vinson J, Teufel K, Wu N: Red wine, dealcoholized red wine, and especially grape juice, inhibit atherosclerosis in a hamster model. Atherosclerosis 156: 67-72, 2000

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Scranton, Scranton, PA, 18510-4626, USA

    J.A. Vinson, M.A. Mandarano, D.L. Shuta & M. Bagchi

  2. Department of Pharmacy Sciences, Creighton University School of Pharmacy and AHP, Omaha, NE, USA

    D. Bagchi

Authors
  1. J.A. Vinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M.A. Mandarano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D.L. Shuta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Bagchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. Bagchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vinson, J., Mandarano, M., Shuta, D. et al. Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacin-bound chromium in a hamster atherosclerosis model. Mol Cell Biochem 240, 99–103 (2002). https://doi.org/10.1023/A:1020611925819

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020611925819

Search

Navigation