Absorption and Metabolism of Urolithin A and Ellagic Acid in Mice and Their Cytotoxicity in Human Colorectal Cancer Cells.

Urolithin A and urolithin B were synthesized and purified to reach 98.1% and 99% purity, respectively, and the structures were identified by NMR. In urolithin A intake analysis, urolithin A was only detectable at 3 h, not at 6-24 h; it suggested that urolithin A was rapidly metabolized to some unknown metabolites. Using UPLC-MS/MS analysis, the metabolites might be urolithin A 3-O-glucuronide, urolithin A 3-sulfate, and urolithin A-sulfate glucuronide. After feeding mice with ellagic acid for consecutive 14 days, ellagic acid contents could be detected in the fecal samples, but not in plasma and liver, and urolithin A was not detected in all samples. It suggests that ellagic acid is not easily absorbed and that the biotransformation of ellagic acid to urolithin A by intestinal flora might be very low. From the cytotoxicity assay, it was found that there was anticancer effect in urolithin A and urolithin B but not in ellagic acid. In contrast, ellagic acid promoted the proliferation of SW480 and SW620 cells.