Ellagitannin metabolites, urolithin <scp>A</scp> glucuronide and its aglycone urolithin <scp>A</scp>, ameliorate <scp>TNF</scp>‐α‐induced inflammation and associated molecular markers in human aortic endothelial cells

Abstract

SCOPE: Numerous in vitro and in vivo studies indicate that ellagitannins exhibit anti-inflammatory, anti-atherosclerotic and anti-angiogenic activity which support their potential preventive effect against cardiovascular diseases. Ellagitannins exhibit low bioavailability and are transformed in the gut to ellagic acid and its microbiota metabolites urolithin A (Uro-A) and urolithin B (Uro-B). Urolithins are found in plasma mostly as glucuronides at low μM concentrations. We investigated whether urolithin glucuronides and their aglycones exhibit vascular protective effects. METHODS AND RESULTS: Human aortic endothelial cells were exposed to tumor necrosis factor alpha and to Uro-A glucuronide, Uro-B glucuronide or their corresponding aglycones at low μM concentrations to determine their effects on monocytes adhesion and endothelial cell migration. The levels of related adhesion cytokines and growth molecular markers were also measured. Uro-A glucuronide (∼5-15 μM) inhibited monocyte adhesion and endothelial cell migration in a significant manner. These effects were associated with a moderate but significant down-regulation of the levels of chemokine (C-C motif) ligand 2 (CCL2) and plasminogen activator inhibitor-1 (PAI-1). Uro-A inhibited endothelial cell migration and was able to decrease the expression of CCL2 and interleukin-8 (IL-8). CONCLUSION: Our results suggest that these metabolites might be involved, at least in part, in the beneficial effects against cardiovascular diseases attributed to the consumption of ellagitannin-containing foods.