Foam cell formation is the hallmark of early atherosclerosis. Lipid uptake by scavenger receptors (SR) in macrophages initiates chronic... » More

Foam cell formation is the hallmark of early atherosclerosis. Lipid uptake by scavenger receptors (SR) in macrophages

initiates chronic proinflammatory cascades linked to atherosclerosis. It has been reported that the upregulation of

cholesterol efflux may be protective in the development of atherosclerosis. Ellagic acid, a polyphenolic compound mostly

found in berries, walnuts, and pomegranates, possesses antioxidative, growth-inhibiting and apoptosis-promoting

activities in cancer cells. However, the antiatherogenic actions of ellagic acid are not well defined. The current study

elucidated oxidized LDL handling of ellagic acid in J774A1 murine macrophages. Noncytotoxic ellagic acid suppressed SRB1

induction and foam cell formation within 6 h after the stimulation of macrophages with oxidized LDL, confirmed by Oil

red O staining of macrophages. Ellagic acid at <5 mmol/L upregulated PPARg and ATP binding cassette transporter-1 in

lipid-laden macrophages, all responsible for cholesterol efflux. In addition, 5 mmol/L ellagic acid accelerated expression and

transcription of the nuclear receptor of liver X receptor-a highly implicated in the PPAR signaling. Furthermore, ellagic acid

promoted cholesterol efflux in oxidized LDL-induced foam cells. These results provide new information that ellagic acid

downregulated macrophage lipid uptake to block foam cell formation of macrophages and boosted cholesterol efflux in

lipid-laden foam cells. Therefore, dietary and pharmacological interventions with berries rich in ellagic acid may be

promising treatment strategies to interrupt the development of atherosclerosis.

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