Abstract: This research was designed to investigate the potential anti-atherogenic effect of urolithin A on macrophage polarization and the formation of macrophage derived-foam cells as well as the underlying molecular mechanisms. It was found that urolithin A could mediate the mRNA expression of different marker genes in M1-type and natural macrophages, indicating its ability to inhibit the polarization of macrophage cell line (RAW264.7) into pro-inflammatory M1-type macrophage and to promote the polarization of macrophage cells into M2 type. The results of oil red O staining revealed that urolithin A inhibited the formation of foam cells derived from macrophages. Real time PCR showed that urolithin A also markedly decreased the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and fatty acid synthase at the transcriptional level. Besides, urolithin A was capable of up-regulating the mRNA expression of the ATP-binding cassette transporters A1 and G1, which was positively associated with macrophage cholesterol efflux. In summary, the findings confirmed the essential role urolithin A plays in macrophage polarization, and further demonstrated the potential molecular mechanisms of urolithin A in preventing foam cell formation and cholesterol synthesis, which are of great significance in investigating and understanding the anti-atherogenic effect of urolithin A in the future.

Key words: urolithin A (Uro-A), macrophage polarization, foam cells, cholesterol, atherosclerosis