Pomegranate Juice Supplementation to Atherosclerotic Mice Reduces Macrophage Lipid Peroxidation, Cellular Cholesterol Accumulation and Development of Atherosclerosis

Abstract

Inhibition of lipid peroxidation contributes to the attenuation of macrophage cholesterol accumulation, foam-cell formation and atherosclerosis. Evidence suggests that nutritional antioxidants such as pomegranate juice (PJ) can contribute to the reduction of oxidative stress and atherogenesis. The goals of the present study were to determine whether such beneficial effects of PJ exist when supplemented to apolipoprotein E-deficient (E(0)) mice with advanced atherosclerosis and to analyze the antiatherosclerotic activity of a tannin-fraction isolated from PJ. Mice (4-mo-old) were supplemented with PJ in their drinking water for 2 mo and compared with age-matched placebo-treated mice, as well as to young (4-mo-old) control mice, for their mouse peritoneal macrophage (MPM) oxidative state, cholesterol flux and mice atherosclerotic lesion size. PJ supplementation reduced each of the proatherogenic variables determined in the present study compared with age-matched placebo-treated mice. It significantly induced serum paraoxonase activity and reduced MPM lipid peroxide content compared with placebo-treated mice and control mice. PJ administration to E(0) mice significantly reduced the oxidized (Ox)-LDL MPM uptake by 31% and MPM cholesterol esterification and increased macrophage cholesterol efflux by 39% compared with age-matched, placebo-treated mice. PJ consumption reduced macrophage Ox-LDL uptake and cholesterol esterification to levels lower than those in 4-mo-old, unsupplemented controls. PJ supplementation to E(0) mice with advanced atherosclerosis reduced the lesion size by 17% compared with placebo-treated mice. In a separate study, supplementation of young (2-mo-old) E(0) mice for 2 mo with a tannin fraction isolated from PJ reduced their atherosclerotic lesion size, paralleled by reduced plasma lipid peroxidation and decreased Ox-LDL MPM uptake. PJ supplementation to mice with advanced atherosclerosis reduced their macrophage oxidative stress, their macrophage cholesterol flux and even attenuated the development of atherosclerosis. Moreover, a tannin-fraction isolated from PJ had a significant antiatherosclerotic activity.

Natural Antioxidant Ingredient From by-Products of Fruits

“…However, Nunez-Selles (2005) reported that phenolic compounds were found in significant concentration in mango seed kernel and barks to be responsible for antioxidant activity. For phenolic constituents in kernel pomegranate fruits are diver than that reported by several researchers, that the major phenolic compounds were punicalagin, ellagic acid, gallo-tannins and anthocyanins (Kaplan et al, 2001;Noda et al, 2002;Cerda et al, 2003). However, the results agree with that the main phenolics in pomegranate were gallic and ellagic acids (Huang et al, 2005).…”

In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice

“…The biological properties associated with pomegranate fruits [7][8][9][10] prompted us to evaluate their major phytochemical ingredients as single purified compounds, punicalagin and EA (Fig. 1), and as combinations, TPT and PJ.…”

“…Pomegranate juice and extracts have been shown to have potent in vitro antioxidant [7,24] and in vivo anti-atherosclerotic properties [8,9,15], attributed to its high content of polyphenols including ETs and EA. Recently, there have also been numerous reports on the in vitro and in vivo anticancer properties of pomegranates [10,[25][26][27][28][29][30].…”

“…Commercial pomegranate juice (PJ) shows potent antioxidant and anti-atherosclerotic properties attributed to its high content of polyphenols including ellagic acid (EA) in its free and bound forms [as ETs and EA glycosides (EAGs)], gallotannins and anthocyanins (cyanidin, delphinidin and pelargonidin glycosides), and other flavonoids (quercetin, kaempferol and luteolin glycosides) [7][8][9][10][11][12]. The most abundant of these polyphenols is punicalagin (Fig.…”

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

“…12 Dietary supplementation of polyphenol-rich pomegranate juice to atherosclerotic mice significantly inhibited the development of atheroclerotic lesions and this may be attributed to the protection of low-density lipoprotein against oxidation. 13,14 Fermented pomegranate juice and coldpressed PFE can reduce prostaglandin and leukotriene formation by inhibition of cyclooxygenase and lipoxygenase activities. 15 Recent studies have shown that pomegranate wine may serve as a potent inhibitor of nuclear factor kappa B (NF-B) in vascular endothelial cells.…”