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Atherosclerosis. 2013 Jan;226(1):110-7. doi: 10.1016/j.atherosclerosis.2012.10.054. Epub 2012 Oct 31.

Pomegranate phytosterol (β-sitosterol) and polyphenolic antioxidant (punicalagin) addition to statin, significantly protected against macrophage foam cells formation.

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1
The Lipid Research Laboratory, Technion-Israel Institute of Technology, Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa 31096, Israel.

Abstract

OBJECTIVE:

To assess the anti-atherogenic effects on macrophage cholesterol biosynthesis rate, and on cellular oxidative stress by the combination of simvastatin with a potent polyphenolic antioxidant (punicalagin), or with a phytosterol (β-sitosterol), or with pomegranate juice (POM, that contains both of them).

METHODS AND RESULTS:

Simvastatin (15 μg/ml) decreased J774A.1 macrophage cholesterol biosynthesis rate by 42% as compared to control cells. The addition to the statin of either punicalagin (15 or 30 μM), or β-sitosterol (50 or 100 μM), increased the inhibitory effect of the statin up to 62% or 57%, respectively. Similarly, the combination of POM and simvastatin, resulted in an inhibitory effect up to 59%. While simvastatin inhibited the rate limiting enzyme HMGCoA-reductase, punicalagin, β-sitosterol or POM inhibited macrophage cholesterol biosynthesis downstream to mevalonate. Simvastatin (15 μg/ml) also modestly decreased macrophage reactive oxygen species (ROS) formation by 11%. In the presence of punicalagin (15 or 30 μM) however, a remarkable further inhibition was noted (by 61% or 79%, respectively). Although β-sitosterol alone showed some pro-oxidant activity, the combination of simvastatin, β-sitosterol and punicalagin, clearly demonstrated a remarkable 73% reduction in ROS production. Similarly, simvastatin + POM decreased the extent of ROS formation by up to 63%. These improved antioxidant effects of the combinations could be related to various anti-oxidative properties of the different compounds, including free radicals scavenging capacity, upregulation of paraoxonase 2, and stimulation of reduced glutathione.

CONCLUSION:

The combination of simvastatin with potent antioxidant and phytosterol (such as present in pomegranate) could lead to attenuation of macrophage foam cell formation and atherogenesis.

[Indexed for MEDLINE]

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