Flavonoids-rich nutrients with potent antioxidant activity prevent atherosclerosis development: the licorice example

Abstract

Background: Macrophage-mediated oxidation of low-density lipoprotein (LDL) has a major role in early atherogenesis, and, thus, intervention means to inhibit this process by flavonoids-rich nutrients (pomegranate, red wine, licorice) are being extensively studied. In the present study, we questioned the ability of the isoflavan glabridin from licorice root to accumulate in macrophages and to affect cell-mediated oxidation of LDL and atherogenesis. Results: Macrophages accumulated glabridin, and this process was time and glabridin dose dependent. In parallel, macrophage-mediated oxidation of LDL was inhibited by up to 80%. Glabridin inhibited superoxides release from MPM by up to 60%, and in glabridin-enriched macrophages, reduced protein kinase C activity by 70% was noted, in comparison to control cells. Translocation of P-47phox, the cytosolic component of NADPH oxidase, to the plasma membrane was substantially inhibited by glabridin. Macrophages (MPM) isolated from the atherosclerotic apolipoprotein E-deficient (E o) mice that consumed glabridin (20 μg/mouse/day) for 6 weeks demonstrated reduced capability to oxidize LDL by 80%, in comparison to placebo-treated mice. This latter phenomenon was associated with a substantial 50% reduction in the mice aortic lesion size. Conclusions: Glabridin accumulation in macrophages affects cell-signaling processes, which are associated with activation of the cellular NADPH oxidase system. These phenomena are responsible for the inhibition of cell-mediated oxidation of LDL and the attenuation of atherosclerosis developments by dietary glabridin.