Copyright © 2012 Michael Aviram and Mira Rosenblat. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

1. C. A. Rice-Evans, N. J. Miller, P. G. Bolwell, P. M. Bramley, and J. B. Pridham, “The relative antioxidant activities of plant-derived polyphenolic flavonoids,” Free Radical Research, vol. 22, no. 4, pp. 375–383, 1995. View at Scopus
2. S. A. B. E. Van Acker, D. J. Van Den Berg, M. N. J. L. Tromp et al., “Structural aspects of antioxidant activity of flavonoids,” Free Radical Biology and Medicine, vol. 20, no. 3, pp. 331–342, 1996. View at Publisher · View at Google Scholar · View at Scopus
3. B. Fuhrman and M. Aviram, “Flavonoids protect LDL from oxidation and attenuate atherosclerosis,” Current Opinion in Lipidology, vol. 12, no. 1, pp. 41–48, 2001. View at Publisher · View at Google Scholar · View at Scopus
4. B. Fuhrman and M. Aviram, “Polyphenols and flavonoids protect LDL against atherogenic modifications,” in Handbook of Antioxidants Biochemical, Nutritional and Clinical Aspects, E. Cadenas and L. Packer, Eds., vol. 16, p. 303, Marcel Dekker, NY, USA, 2nd edition, 2001.
5. M. Rosenblat, P. Belinky, J. Vaya et al., “Macrophage enrichment with the isoflavan glabridin inhibits NADPH oxidase-induced cell-mediated oxidation of low density lipoprotein. A possible role for protein kinase C,” Journal of Biological Chemistry, vol. 274, no. 20, pp. 13790–13799, 1999. View at Publisher · View at Google Scholar · View at Scopus
6. M. G. L. Hertog, D. Kromhout, C. Aravanis, et al., “Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study,” Archives of Internal Medicine, vol. 155, no. 4, pp. 381–386, 1995. View at Publisher · View at Google Scholar
7. P. Knekt, J. Kumpulainen, R. Järvinen et al., “Flavonoid intake and risk of chronic diseases,” American Journal of Clinical Nutrition, vol. 76, no. 3, pp. 560–568, 2002. View at Scopus
8. P. Knekt, R. Järvinen, A. Reunanen, and J. Maatela, “Flavonoid intake and coronary mortality in Finland: a cohort study,” British Medical Journal, vol. 312, no. 7029, pp. 478–481, 1996. View at Scopus
9. S. Renaud and M. De Lorgeril, “Wine, alcohol, platelets, and the French paradox for coronary heart disease,” Lancet, vol. 339, no. 8808, pp. 1523–1526, 1992. View at Publisher · View at Google Scholar · View at Scopus
10. M. Aviram, “Antioxidants in restenosis and atherosclerosis,” Current Interventional Cardiology Reports, vol. 1, p. 66, 1999.
11. T. Hayek, B. Fuhrman, J. Vaya et al., “Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 11, pp. 2744–2752, 1997. View at Scopus
12. M. Aviram and B. Fuhrman, “Wine flavonoids, LDL cholesterol oxidation and atherosclerosis,” in Wine: A Scientific explorAtion, M. Sandler and R. M. Pinder, Eds., p. 140, Taylor and Francis, London, UK, 2003.
13. B. Fuhrman, S. Buch, J. Vaya et al., “Licorice extract and its major polyphenol glabridin protect low-density lipoprotein against lipid peroxidation: In vitro and ex vivo studies in humans and in atherosclerotic apolipoprotein E-deficient mice,” American Journal of Clinical Nutrition, vol. 66, no. 2, pp. 267–275, 1997. View at Scopus
14. M. Aviram, J. Vaya, and B. Fuhrman, “Licorice root flavonoid antioxidants reduce LDL oxidation and attenuate cardiovascular diseases,” in Herbal Medicines: Molecular Basis of Biological Activity and Health, L. Packer, B. Halliwel, and C. N. Ong, Eds., chapter 27, p. 595, Marcel Dekker, NY, USA, 2004.
15. B. Fuhrman, N. Volkova, R. Coleman, and M. Aviram, “Grape powder polyphenols attenuate atherosclerosis development in apolipoprotein E deficient (E⁰) mice and reduce macrophage atherogenicity,” Journal of Nutrition, vol. 135, no. 4, pp. 722–728, 2005. View at Scopus
16. B. Fuhrman, M. Rosenblat, T. Hayek, R. Coleman, and M. Aviram, “Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice,” Journal of Nutrition, vol. 130, no. 5, pp. 1124–1131, 2000. View at Scopus
17. P. Langley, “Why a pomegranate?” British Medical Journal, vol. 321, no. 7269, pp. 1153–1154, 2000. View at Scopus
18. M. Aviram, “Polypyhenols from pomegranate juice, red wine and licorice root protect against lipids peroxidation and attenuate cardiovascular diseases,” in Polyphenols, S. Martens, D. Treutter, and G. Forkmann, Eds., Proceedings of the 20th International Conference on Polyphenols, p. 158, Freising-Weihenstephan, Germany, 2002.
19. M. I. Gil, F. A. Tomas-Barberan, B. Hess-Pierce, D. M. Holcroft, and A. A. Kader, “Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing,” Journal of Agricultural and Food Chemistry, vol. 48, no. 10, pp. 4581–4589, 2000. View at Publisher · View at Google Scholar · View at Scopus
20. C. Ben Nasr, N. Ayed, and M. Metche, “Quantitative determination of the polyphenolic content of pomegranate peel,” Zeitschrift fur Lebensmittel -Untersuchung und -Forschung, vol. 203, no. 4, pp. 374–378, 1996. View at Scopus
21. M. Aviram, “Pomegranate juice as a major source for polyphenolic flavonoids and it is most potent antioxidant against LDL oxidation and atherosclerosis,” in Proceedings of the 11th Biennal Meeting of the Society for Free Radical Research International, Monduzzi, Ed., p. 523, MEDIMOND Inc, Paris, France, July 2002.
22. M. Aviram, M. Aviram, B. Fuhrman, M. Rosenblat, et al., “Pomegranate juice polyphenols decreases oxidative stress, low-density lipoprotein atherogenic modifications and atherosclerosis,” Free Radical Research, vol. 36, supplement 1, pp. 72–73, 2002.
23. M. Aviram, L. Dornfeld, M. Kaplan et al., “Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans,” Drugs under Experimental and Clinical Research, vol. 28, no. 2-3, pp. 49–62, 2002. View at Scopus
24. B. Cerdá, R. Llorach, J. J. Cerón, J. C. Espín, and F. A. Tomás-Barberán, “Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice,” European Journal of Nutrition, vol. 42, no. 1, pp. 18–28, 2003. View at Publisher · View at Google Scholar · View at Scopus
25. B. Cerdá, J. J. Cerón, F. A. Tomás-Barberán, and J. C. Espín, “Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic,” Journal of Agricultural and Food Chemistry, vol. 51, no. 11, pp. 3493–3501, 2003. View at Publisher · View at Google Scholar · View at Scopus
26. N. P. Seeram, R. Lee, and D. Heber, “Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice,” Clinica Chimica Acta, vol. 348, no. 1-2, pp. 63–68, 2004. View at Publisher · View at Google Scholar · View at Scopus
27. A. Pérez-Vicente, A. Gil-Izquierdo, and C. García-Viguera, “In vitro gastrointestinal digestion study of pomegranate juice phenolic compounds, anthocyanins, and vitamin C,” Journal of Agricultural and Food Chemistry, vol. 50, no. 8, pp. 2308–2312, 2002. View at Publisher · View at Google Scholar · View at Scopus
28. M. Aviram, L. Dornfeld, M. Rosenblat et al., “Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice,” American Journal of Clinical Nutrition, vol. 71, no. 5, pp. 1062–1076, 2000. View at Scopus
29. M. Kaplan, T. Hayek, A. Raz et al., “Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis,” Journal of Nutrition, vol. 131, no. 8, pp. 2082–2089, 2001. View at Scopus
30. F. De Nigris, S. Williams-Ignarro, L. O. Lerman et al., “Beneficial effects of pomegranate juice on oxidation-sensitive genes and endothelial nitric oxide synthase activity at sites of perturbed shear stress,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 13, pp. 4896–4901, 2005. View at Publisher · View at Google Scholar · View at Scopus
31. M. D. Sumner, M. Elliott-Eller, G. Weidner et al., “Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease,” American Journal of Cardiology, vol. 96, no. 6, pp. 810–814, 2005. View at Publisher · View at Google Scholar · View at Scopus
32. M. Aviram, M. Rosenblat, D. Gaitini et al., “Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation,” Clinical Nutrition, vol. 23, no. 3, pp. 423–433, 2004. View at Publisher · View at Google Scholar · View at Scopus
33. M. H. Davidson, K. C. Maki, M. R. Dicklin et al., “Effects of consumption of pomegranate juice on carotid intima-media thickness in men and women at moderate risk for coronary heart disease,” American Journal of Cardiology, vol. 104, no. 7, pp. 936–942, 2009. View at Publisher · View at Google Scholar · View at Scopus
34. N. P. Seeram, M. Aviram, Y. Zhang et al., “Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States,” Journal of Agricultural and Food Chemistry, vol. 56, no. 4, pp. 1415–1422, 2008. View at Publisher · View at Google Scholar · View at Scopus
35. M. Rosenblat, N. Volkova, J. Attias, R. Mahamid, and M. Aviram, “Consumption of polyphenolic-rich beverages (mostly pomegranate and black currant juices) by healthy subjects for a short term increased serum antioxidant status, and the serum's ability to attenuate macrophage cholesterol accumulation,” Food and Function, vol. 1, no. 1, pp. 99–109, 2010. View at Publisher · View at Google Scholar · View at Scopus
36. M. Rosenblat, T. Hayek, and M. Aviram, “Anti-oxidative effects of pomegranate juice (PJ) consumption by diabetic patients on serum and on macrophages,” Atherosclerosis, vol. 187, no. 2, pp. 363–371, 2006. View at Publisher · View at Google Scholar · View at Scopus
37. W. Rock, M. Rosenblat, R. Miller-Lotan, A. P. Levy, M. Elias, and M. Aviram, “Consumption of Wonderful variety pomegranate juice and extract by diabetic patients increases paraoxonase 1 association with high-density lipoprotein and stimulates its catalytic activities,” Journal of Agricultural and Food Chemistry, vol. 56, no. 18, pp. 8704–8713, 2008. View at Publisher · View at Google Scholar · View at Scopus
38. B. Fuhrman, N. Volkova, and M. Aviram, “Pomegranate juice polyphenols increase recombinant paraoxonase-1 binding to high-density lipoprotein: studies in vitro and in diabetic patients,” Nutrition, vol. 26, no. 4, pp. 359–366, 2010. View at Publisher · View at Google Scholar · View at Scopus
39. M. Aviram, M. Rosenblat, S. Billecke et al., “Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants,” Free Radical Biology and Medicine, vol. 26, no. 7-8, pp. 892–904, 1999. View at Publisher · View at Google Scholar · View at Scopus
40. J. Khateeb, A. Gantman, A. J. Kreitenberg, M. Aviram, and B. Fuhrman, “Paraoxonase 1 (PON1) expression in hepatocytes is upregulated by pomegranate polyphenols: a role for PPAR-γ pathway,” Atherosclerosis, vol. 208, no. 1, pp. 119–125, 2010. View at Publisher · View at Google Scholar · View at Scopus
41. M. Aviram, “Review of human studies on oxidative damage and antioxidant protection related to cardiovascular diseases,” Free Radical Research, vol. 33, pp. S85–S97, 2000. View at Scopus
42. J. A. Berliner, M. Navab, A. M. Fogelman et al., “Atherosclerosis: basic mechanisms: oxidation, inflammation, and genetics,” Circulation, vol. 91, no. 9, pp. 2488–2496, 1995. View at Scopus
43. B. Fuhrman, J. Oiknine, and M. Aviram, “Iron induces lipid peroxidation in cultured macrophages, increases their ability to oxidatively modify LDL, and affects their secretory properties,” Atherosclerosis, vol. 111, no. 1, pp. 65–78, 1994. View at Publisher · View at Google Scholar · View at Scopus
44. B. Fuhrman, O. Judith, S. Keidar, L. Ben-Yaish, M. Kaplan, and M. Aviram, “Increased uptake of LDL by oxidized macrophages is the result of an initial enhanced LDL receptor activity and of a further progressive oxidation of LDL,” Free Radical Biology and Medicine, vol. 23, no. 1, pp. 34–46, 1997. View at Publisher · View at Google Scholar · View at Scopus
45. B. Fuhrman, N. Volkova, and M. Aviram, “Oxidative stress increases the expression of the CD36 scavenger receptor and the cellular uptake of oxidized low-density lipoprotein in macrophages from atherosclerotic mice: protective role of antioxidants and of paraoxonase,” Atherosclerosis, vol. 161, no. 2, pp. 307–316, 2002. View at Publisher · View at Google Scholar · View at Scopus
46. O. Rozenberg, A. Howell, and M. Aviram, “Pomegranate juice sugar fraction reduces macrophage oxidative state, whereas white grape juice sugar fraction increases it,” Atherosclerosis, vol. 188, no. 1, pp. 68–76, 2006. View at Publisher · View at Google Scholar · View at Scopus
47. B. B. Aggarwal and S. Shishodia, “Suppression of the nuclear factor-κB activation pathway by spice-derived phytochemicals: reasoning for seasoning,” Annals of the New York Academy of Sciences, vol. 1030, pp. 434–441, 2004. View at Publisher · View at Google Scholar · View at Scopus
48. S. Y. Schubert, I. Neeman, and N. Resnick, “A novel mechanism for the inhibition of NF-kappaB activation in vascular endothelial cells by natural antioxidants.,” The FASEB Journal, vol. 16, no. 14, pp. 1931–1933, 2002. View at Scopus
49. S. Y. Schubert, E. P. Lansky, and I. Neeman, “Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids,” Journal of Ethnopharmacology, vol. 66, no. 1, pp. 11–17, 1999. View at Publisher · View at Google Scholar · View at Scopus
50. C. J. Ng, D. J. Wadleigh, A. Gangopadhyay et al., “Paraoxonase 2 is aubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein,” Journal of Biological Chemistry, vol. 276, no. 48, pp. 44444–44449, 2001. View at Publisher · View at Google Scholar · View at Scopus
51. M. Rosenblat, D. Draganov, C. E. Watson, C. L. Bisgaier, B. N. La Du, and M. Aviram, “Mouse macrophage paraoxonase 2 activity is increased whereas cellular paraoxonase 3 activity is decreased under oxidative stress,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 3, pp. 468–474, 2003. View at Publisher · View at Google Scholar · View at Scopus
52. C. J. Ng, N. Bourquard, V. Grijalva et al., “Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2,” Journal of Biological Chemistry, vol. 281, no. 40, pp. 29491–29500, 2006. View at Publisher · View at Google Scholar · View at Scopus
53. M. Rosenblat, R. Coleman, S. T. Reddy, and M. Aviram, “Paraoxonase 2 attenuates macrophage triglyceride accumulation via inhibition of diacylglycerol acyltransferase 1,” Journal of Lipid Research, vol. 50, no. 5, pp. 870–879, 2009. View at Publisher · View at Google Scholar · View at Scopus
54. E. Meilin, M. Aviram, and T. Hayek, “Paraoxonase 2 (PON2) decreases high glucose-induced macrophage triglycerides (TG) accumulation, via inhibition of NADPH-oxidase and DGAT1 activity: studies in PON2-deficient mice,” Atherosclerosis, vol. 208, no. 2, pp. 390–395, 2010. View at Publisher · View at Google Scholar · View at Scopus
55. M. Shiner, B. Fuhrman, and M. Aviram, “Macrophage paraoxonase 2 (PON2) expression is up-regulated by pomegranate juice phenolic anti-oxidants via PPARγ and AP-1 pathway activation,” Atherosclerosis, vol. 195, no. 2, pp. 313–321, 2007. View at Publisher · View at Google Scholar · View at Scopus
56. M. Rosenblat, N. Volkova, and M. Aviram, “Pomegranate juice (PJ) consumption antioxidative properties on mouse macrophages, but not PJ beneficial effects on macrophage cholesterol and triglyceride metabolism, are mediated via PJ-induced stimulation of macrophage PON2,” Atherosclerosis, vol. 212, no. 1, pp. 86–92, 2010. View at Publisher · View at Google Scholar · View at Scopus
57. M. Aviram, “Interaction of oxidized low density lipoprotein with macrophages in atherosclerosis, and the antiatherogenicity of antioxidants,” European Journal of Clinical Chemistry and Clinical Biochemistry, vol. 34, no. 8, pp. 599–608, 1996. View at Scopus
58. D. Steinberg, “Low density lipoprotein oxidation and its pathobiological significance,” Journal of Biological Chemistry, vol. 272, no. 34, pp. 20963–20966, 1997. View at Publisher · View at Google Scholar · View at Scopus
59. J. L. Goldstein and M. S. Brown, “Regulation of the mevalonate pathway,” Nature, vol. 343, no. 6257, pp. 425–430, 1990. View at Publisher · View at Google Scholar · View at Scopus
60. M. S. Brown and J. L. Goldstein, “A receptor-mediated pathway for cholesterol homeostasis,” Science, vol. 232, no. 4746, pp. 34–47, 1986. View at Scopus
61. M. Krieger, “The best of cholesterols, the worst of cholesterols: a tale of two receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 8, pp. 4077–4080, 1998. View at Publisher · View at Google Scholar · View at Scopus
62. B. Fuhrman, N. Volkova, and M. Aviram, “Pomegranate juice inhibits oxidized LDL uptake and cholesterol biosynthesis in macrophages,” Journal of Nutritional Biochemistry, vol. 16, no. 9, pp. 570–576, 2005. View at Publisher · View at Google Scholar · View at Scopus
63. P. Cullen, “Evidence that triglycerides are an independent coronary heart disease risk factor,” American Journal of Cardiology, vol. 86, no. 9, pp. 943–949, 2000. View at Publisher · View at Google Scholar · View at Scopus
64. B. Lundberg, “Chemical composition and physical state of lipid deposits in atherosclerosis,” Atherosclerosis, vol. 56, no. 1, pp. 93–110, 1985. View at Scopus
65. A. Aronis, Z. Madar, and O. Tirosh, “Mechanism underlying oxidative stress-mediated lipotoxicity: Exposure of J774.2 macrophages to triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular necrosis,” Free Radical Biology and Medicine, vol. 38, no. 9, pp. 1221–1230, 2005. View at Publisher · View at Google Scholar · View at Scopus
66. M. Rosenblat and M. Aviram, “Pomegranate juice protects macrophages from triglyceride accumulation: inhibitory effect on DGAT1 activity and on triglyceride biosynthesis,” Annals of Nutrition and Metabolism, vol. 58, no. 1, pp. 1–9, 2011. View at Publisher · View at Google Scholar · View at Scopus
67. R. Tzulker, I. Glazer, I. Bar-Ilan, D. Holland, M. Aviram, and R. Amir, “Antioxidant activity, polyphenol content, and related compounds in different fruit juices and homogenates prepared from 29 different pomegranate accessions,” Journal of Agricultural and Food Chemistry, vol. 55, no. 23, pp. 9559–9570, 2007. View at Publisher · View at Google Scholar · View at Scopus
68. N. Seeram, R. Lee, M. Hardy, and D. Heber, “Rapid large scale purification of ellagitannins from pomegranate husk, a by-product of the commercial juice industry,” Separation and Purification Technology, vol. 41, no. 1, pp. 49–55, 2005. View at Publisher · View at Google Scholar · View at Scopus
69. M. Rosenblat, N. Volkova, R. Coleman, and M. Aviram, “Pomegranate byproduct administration to apolipoprotein E-deficient mice attenuates atherosclerosis development as a result of decreased macrophage oxidative stress and reduced cellular uptake of oxidized low-density lipoprotein,” Journal of Agricultural and Food Chemistry, vol. 54, no. 5, pp. 1928–1935, 2006. View at Publisher · View at Google Scholar · View at Scopus
70. M. Aviram, N. Volkova, R. Coleman et al., “Pomegranate phenolics from the peels, arils, and flowers are antiatherogenic: studies in vivo in atherosclerotic apolipoprotein E-deficient (E⁰) mice and in vitro in cultured macrophages and lipoproteins,” Journal of Agricultural and Food Chemistry, vol. 56, no. 3, pp. 1148–1157, 2008. View at Publisher · View at Google Scholar · View at Scopus