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ISHS Acta Horticulturae 744: I International Symposium on Human Health Effects of Fruits and Vegetables

POMEGRANATE AND CARDIOVASCULAR DISEASES: POMEGRANATE JUICE POLYPHENOLIC ANTIOXIDANTS PROTECT AGAINST OXIDATIVE STRESS AND ATHEROSCLEROSIS DEVELOPMENT

Authors:   B. Fuhrman, M. Aviram
Keywords:   pomegranate juice, atherosclerosis, LDL oxidation, oxidative stress, paraoxonase 1 (PON1), macrophages, atherosclerotic mice
Abstract:
Atherosclerosis results from multiple interactive risk factors, including hypertension, increased plasma LDL level and LDL oxidation. We analyzed antiatherogenicity of pomegranate juice (PJ), which is rich in potent antioxidants, on atherosclerosis development in relation to lipoprotein oxidation and macrophage atherogenicity in humans (healthy subjects and atherosclerotic patients) and in the atherosclerotic apolipoprotein E-deficient (E) mice. In vitro studies demonstrated a PJ dose-dependent antioxidant capability against lipid peroxidation in plasma (by 33%), in LDL (by 43%), and in HDL (by 22%). PJ consumption by hypertensive patients reduced their systolic blood pressure (by 6%), along with inhibition (by 40%) of angiotensin converting enzyme (ACE). PJ supplementation to E mice reduced their atherosclerotic lesion size by 44% and the number of foam cells in their lesion. Consumption of PJ by ten patients with carotid artery stenosis (CAS) for one year reduced the patients’ carotid intima-media thickness (IMT) by 32%. These effects were associated with ex-vivo reduced lipid peroxidation in plasma and in isolated lipoproteins in humans and mice. Furthermore, PJ consumption by humans increased the activity of their serum paraoxonase (PON1), an HDL-associated esterase that protects against lipid peroxidation. Macrophage atherogenicity was studied in mouse peritoneal macrophages (MPM) harvested from E mice. Following PJ consumption, uptake of oxidized LDL and cell-mediated oxidation of LDL by macrophages was reduced by 88% and by 20%, respectively, in association with reduced cellular lipid peroxidation, reduced superoxide anion release due to decreased NADPH-oxidase activation, and elevated glutathione content. In vitro studies demonstrated that PJ reduced macrophage Ox-LDL degradation by 40%, and macrophage cholesterol biosynthesis by 50%. Taken together, the results of the above studies demonstrate that PJ consumption has very potent anti-atherogenic properties, which could be associated mainly with PJ hydrolysable tannin anti-oxidative properties.

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