Pomegranate Phenolics from the Peels, Arils, and Flowers Are Antiatherogenic: Studiesin Vivoin Atherosclerotic Apolipoprotein E-Deficient (E0) Mice andin Vitroin Cultured Macrophages and Lipoproteins

We have analyzed in vivo and in vitro the antiatherogenic properties and mechanisms of action of all pomegranate fruit parts: peels (POMxl, POMxp), arils (POMa), seeds (POMo), and flowers (POMf), in comparison to whole fruit juice (PJ). Atherosclerotic E0 mice consumed POM extracts [200 µg of gallic acid equivalents (GAE)/mouse/day] for 3 months. Blood samples, peritoneal macrophages (MPM), and aortas were then collected. All POM extracts possess antioxidative properties in vitro. After consumption of PJ, POMxl, POMxp, POMa, or POMf by E0 mice, the atherosclerotic lesion area was significantly decreased by 44, 38, 39, 6, or 70%, respectively, as compared to placebo-treated group, while POMo had no effect. POMf consumption reduced serum lipids, and glucose levels by 18–25%. PJ, POMxl, POMxp, POMf, or POMa consumption resulted in a significant decrement, by 53, 42, 35, 27, or 13%, respectively, in MPM total peroxides content, and increased cellular paraoxonase 2 (PON2) activity, as compared to placebo-treated mice. The uptake rates of oxidized-LDL by E0-MPM were significantly reduced by ∼15% after consumption of PJ, POMxl, or POMxp. Similar results were obtained on using J774A.1 macrophage cell line. Finally, pomegranate phenolics (punicalagin, punicalin, gallic acid, and ellagic acid), as well as pomegranate unique complexed sugars, could mimic the antiatherogenic effects of pomegranate extracts. We conclude that attenuation of atherosclerosis development by some of the POM extracts and, in particular, POMf, could be related to the combined beneficial effects on serum lipids levels and on macrophage atherogenic properties.