A Novel Candidate for Prevention and Treatment of Atherosclerosis: Urolithin B Decreases Lipid Plaque Deposition in apoE−/− Mice and Increases Early Stages of Reverse Cholesterol Transport in ox‐LDL Treated Macrophages Cells

SCOPE: HDL cholesterol is inversely related to the incidence of atherosclerosis. Polyphenols including ellagitannins have been shown to exert antiatherogenic properties. Urolithin B is formed from ellagitannins by components of the gut microbiota, and urolithins might be involved in beneficial effects against cardiovascular diseases in vitro. In this study, the influence of urolithin B on several parameters involved in the lipid plaque deposition and the reverse cholesterol transport is investigated. METHODS AND RESULTS: In apoE-/- mice and two different macrophage cell lines, the influence of urolithin B and its phase II conjugated metabolite on lipid plaque deposition, cholesterol uptake, and expression of ABCA1 and SR-BI is tested. It is shown that urolithin B decreases lipid plaque deposition, both urolithin B and urolithin B sulfate modulate expression of SR-BI and ABCA1, and cholesterol efflux increases from cholesterol laden macrophages to HDL particles as well as to reverse lipid uptake by stimulated THP-1 macrophages. CONCLUSIONS: Urolithin B can decrease lipid plaque deposition, and urolithin B and urolithin B sulfate are able to induce reverse cholesterol transport by influencing expression of key proteins of this pathway. Urolithin B may represent the basis for development of new drugs for prevention and treatment of atherosclerosis in humans.