Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development ofatherosclerosis

Inhibition of lipid peroxidation contributes to the attenuation of macropha ge cholesterol accumulation, foam-cell formation and atherosclerosis. Evide nce suggests that nutritional antioxidants such as pomegranate juice (PJ) c an contribute to the reduction of oxidative stress and atherogenesis. The g oals of the present study were to determine whether such beneficial effects of PJ exist when supplemented to apolipoprotein E-deficient (E degrees) mi ce with advanced atherosclerosis and to analyze the antiatherosclerotic act ivity of a tannin-fraction isolated from PJ. Mice (4-mo-old) were supplemen ted 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 thei r mouse peritoneal macrophage (MPM) oxidative state, cholesterol flux and m ice atherosclerotic lesion size. PJ supplementation reduced each of the pro atherogenic variables determined in the present study compared with age-mat ched placebo-treated mice. It significantly induced serum paraoxonase activ ity and reduced MPM lipid peroxide content compared with placebo-treated mi ce and control mice. PJ administration to E degrees mice significantly redu ced the oxidized (Ox)-LDL MPM uptake by 31% and MPM cholesterol esterificat ion and increased macrophage cholesterol eff lux by 39% compared with age-m atched, placebo-treated mice. PJ consumption reduced macrophage Ox-LDL upta ke and cholesterol esterification to levels lower than those in 4-mo-old, u nsupplemented controls. PJ supplementation to E degrees mice with advanced atherosclerosis reduced the lesion size by 17% compared with placebo-treate d mice. In a separate study, supplementation of young (2-mo-old) E degrees mice for 2 mo with a tannin fraction isolated from PJ reduced their atheros clerotic lesion size, paralleled by reduced plasma lipid peroxidation and d ecreased Ox-LDL MPM uptake. PJ supplementation to mice with advanced athero sclerosis reduced their macrophage oxidative stress, their macrophage chole sterol flux and even attenuated the development of atherosclerosis. Moreove r, a tannin-fraction isolated from PJ had a significant antiatherosclerotic activity.