Pomegranate juice inhibits oxidized LDL uptake and cholesterol biosynthesis in macrophages.
Macrophage cholesterol accumulation and foam cell formation are the hallmarks of early atherogenesis. Pomegranate juice (PJ) was shown to inhibit macrophage foam cell formation and development of atherosclerotic lesions. The aim of this study was to elucidate possible mechanisms by which PJ reduces cholesterol accumulation in macrophages. J774.A1 macrophages were preincubated with PJ followed by analysis of cholesterol influx [evaluated as LDL or as oxidized LDL (Ox-LDL) cellular degradation], cholesterol efflux and cholesterol biosynthesis. Preincubation of macrophages with PJ resulted in a significant reduction (P<.01) in Ox-LDL degradation by 40%. On the contrary, PJ had no effect on macrophage degradation of native LDL or on macrophage cholesterol efflux. Macrophage cholesterol biosynthesis was inhibited by 50% (P<.01) after cell incubation with PJ. This inhibition, however, was not mediated at the 3-hydroxy-3 methylglutaryl coenzyme A reductase level along the biosynthetic pathway. We conclude that PJ-mediated suppression of Ox-LDL degradation and of cholesterol biosynthesis in macrophages can lead to reduced cellular cholesterol accumulation and foam cell formation.
Fuhrman
Bianca
B
Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa 31096, Israel.
Volkova
Nina
N
Aviram
Michael
M
D000818:Animals; D001628:Beverages; D018955:CD36 Antigens / Q000187:drug effects / Q000235:genetics; D002784:Cholesterol / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005487:Foam Cells / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects / Q000235:genetics; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D029561:Lythraceae; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects
D018955:CD36 Antigens; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases