Pomegranate Protection against Cardiovascular Diseases

Figure 13

Major pathways by which pomegranate polyphenols inhibit macrophage foam cell formation and atherosclerosis development. Pomegranate polyphenols are the most potent antioxidants, and they directly inhibit LDL oxidation (#1). Pomegranate increases paraoxonase1 (PON1) liver expression and serum activity, thereby increasing hydrolysis of already formed lipid peroxides in oxidized LDL (Ox-LDL) (#2). Pomegranate polyphenols protect macrophages from cholesterol accumulation by several mechanisms: decrement in cholesterol influx, by inhibition of Ox-LDL uptake via the cells scavenger receptor CD36 (#3), or by inhibition of cholesterol biosynthesis rate (#4), or by stimulation of HDL-mediated cholesterol efflux from macrophages (#5). PJ polyphenols upregulate macrophage paraoxonase 2 (PON2) expression (#6), leading to reduction in macrophage oxidative stress (#7), and inhibition of reactive oxygen species (ROS), or reactive nitrogen species (RNS) production and release from the cells, which can lead to inhibition of LDL oxidation by the cells (#8). Pomegranate polyphenols also inhibit macrophage triglyceride (TG) biosynthesis rate (#9), thus reducing also TG accumulation in macrophages. Altogether, these antiatherogenic effects of PJ attenuate macrophage conversion into foam cells, and the development of atherosclerotic lesion (#10). CE, cholesterol ester; UC, unesterified cholesterol; TG, triglycerides, SR, scavenger receptor, (+), stimulation; (−), inhibition.