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


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).


CONCLUSIONS
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.
Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
Juan A
JA
Giménez-Bastida
Antonio
A
González-Sarrías
Mar
M
Larrosa
Francisco
F
Tomás-Barberán
Juan C
JC
Espín
María-Teresa
MT
García-Conesa
D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D020719:Glucuronides / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects* / Q000494:pharmacology
C576587:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one glucuronide; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D003374:Coumarins; D016207:Cytokines; D020719:Glucuronides; D047348:Hydrolyzable Tannins; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D014409:Tumor Necrosis Factor-alpha; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one