Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A, ameliorate TNF-α-induced inflammation and associated molecular markers in human aortic endothelial cells

ScopeNumerous 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 mu M concentrations. We investigated whether urolithin glucuronides and their aglycones exhibit vascular protective effects. Methods and resultsHuman aortic endothelial cells were exposed to tumor necrosis factor alpha and to Uro-A glucuronide, Uro-B glucuronide or their corresponding aglycones at low mu M 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 (similar to 515 mu M) 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 (CC 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). ConclusionOur 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.