Dissimilar in vitro and in vivo effects of ellagic acid and its microbiota-derived metabolites, urolithins, on the cytochrome P450 1A1.
This research shows that the dietary polyphenol ellagic acid (EA) and its colonic metabolites, urolithin-A (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one, Uro-A) and urolithin-B (3-hydroxy-6H-dibenzo[b,d]pyran-6-one, Uro-B), modulate phase I and phase II detoxifying enzymes in colon cancer Caco-2 cells. EA and the urolithins, at micromolar concentrations achievable in the colon from the diet, induced the expression and activity of CYP1A1 and UGT1A10 and inhibited several sulfotransferases. As a result, the synthesis of glucuronides was favored over sulfated conjugates in the treated cells. In situ exposure to these compounds dissolved in buffer also led to the induction of CYP1A1 in the rat colon. However, in situ exposure to the compounds dissolved in oil or oral supplementation of the single compounds or pomegranate extract (PE) added to the feed failed to induce CYP1A1 in the colon mucosa. These results suggest that EA and urolithins may exert some blocking chemopreventive effects in the colon but that this effect is critically affected by interfering factors, such as the food matrix nature.
González-Sarrías
Antonio
A
Department of Food Science and Technology, Centro de Edafología y Biología Aplicada del Segura-Consejo Superior de Investigaciones Científicas, Murcia, Spain.
Azorín-Ortuño
María
M
Yáñez-Gascón
María-Josefa
MJ
Tomás-Barberán
Francisco A
FA
García-Conesa
María-Teresa
MT
Espín
Juan-Carlos
JC
D000818:Animals; D018938:Caco-2 Cells; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D004610:Ellagic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D029561:Lythraceae / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D003374:Coumarins; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D004610:Ellagic Acid; D019363:Cytochrome P-450 CYP1A1