title: Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages.
abstract: High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25-4 μM). Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels.
authors: Department of Oxidative Stress and Human Diseases, MIGAL-Galilee Research Institute, 11016 Kiryat Shmona, Israel; Tel-Hai College, 12208 Upper Galilee, Israel; Faculty of Medicine in the Galilee, Bar-Ilan University, 1311502 Safed, Israel.
authors: Dana
authors: D
authors: Atrahimovich
authors: Department of Oxidative Stress and Human Diseases, MIGAL-Galilee Research Institute, 11016 Kiryat Shmona, Israel; Tel-Hai College, 12208 Upper Galilee, Israel.
authors: Soliman
authors: S
authors: Khatib
authors: Faculty of Medicine in the Galilee, Bar-Ilan University, 1311502 Safed, Israel; Eliachar Research Laboratory, Western Galilee Hospital, 22100 Nahariya, Israel.
authors: Shifra
authors: S
authors: Sela
authors: Department of Oxidative Stress and Human Diseases, MIGAL-Galilee Research Institute, 11016 Kiryat Shmona, Israel; Tel-Hai College, 12208 Upper Galilee, Israel.
authors: Jacob
authors: J
authors: Vaya
authors: Faculty of Medicine in the Galilee, Bar-Ilan University, 1311502 Safed, Israel.
authors: Abraham O
authors: 0000-0001-7436-3515
authors: AO
authors: Samson
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000378:metabolism / Q000494:pharmacology*; D053299:Apolipoprotein B-100 / Q000378:metabolism; D001665:Binding Sites; D001692:Biological Transport; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D047348:Hydrolyzable Tannins / Q000378:metabolism / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D010636:Phenols / Q000494:pharmacology; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D047348:Hydrolyzable Tannins; D007529:Isoflavones; D008077:Lipoproteins, LDL; D010636:Phenols; C115642:punicalagin; C107601:glabridin