Urolithins, Ellagic Acid-Derived Metabolites Produced by Human Colonic Microflora, Exhibit Estrogenic and Antiestrogenic Activities
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- 作者：Mar Larrosa ; Antonio Gonzá ; lez-Sarrí ; as ; Marí ; a Teresa Garcí ; a-Conesa ; Francisco A. Tomá ; s-Barberá ; n ; and Juan Carlos Espí ; n
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2006
- 出版时间：March 8, 2006
- 年：2006
- 卷：54
- 期：5
- 页码：1611 - 1620
- 全文大小：517K
- 年卷期：v.54,no.5(March 8, 2006)
- ISSN：1520-5118
文摘
Urolithins A and B (hydroxy-6H-dibenzo[b,d]pyran-6-one derivatives) are colonic microflora metabolitesrecently proposed as biomarkers of human exposure to dietary ellagic acid derivatives. Molecularmodels suggest that urolithins could display estrogenic and/or antiestrogenic activity. To this purpose,both urolithins and other known phytoestrogens (genistein, daidzein, resveratrol, and enterolactone)were assayed to evaluate the capacity to induce cell proliferation on the estrogen-sensitive humanbreast cancer MCF-7 cells as well as the ability to bind to 
- and 
-estrogen receptors. Both urolithinsA and B showed estrogenic activity in a dose-dependent manner even at high concentrations (40
M), without antiproliferative or toxic effects, whereas the other phytoestrogens inhibited cellproliferation at high concentrations. Overall, urolithins showed weaker estrogenic activity than theother phytoestrogens. However, both urolithins displayed slightly higher antiestrogenic activity(antagonized the growth promotion effect of 17--estradiol in a dose-dependent manner) than theother phytoestrogens. The IC50 values for the ER and ER binding assays were 0.4 and 0.75 Mfor urolithin A; 20 and 11 M for urolithin B; 3 and 0.02 for genistein; and 2.3 and 1 for daidzein,respectively; no binding was detected for resveratrol and enterolactone. Urolithins A and B enteredinto MCF-7 cells and were metabolized to yield mainly urolithin-sulfate derivatives. These results,together with previous studies regarding absorption and metabolism of dietary ellagitannins and ellagicacid in humans, suggest that the gut microflora metabolites urolithins are potential endocrine-disruptingmolecules, which could resemble other described "enterophytoestrogens" (microflora-derivedmetabolites with estrogenic/antiestrogenic activity). Further research is warranted to evaluate thepossible role of ellagitannins and ellagic acid as dietary "pro-phytoestrogens".Keywords: Breast cancer; phytoestrogen; hydroxy-6H-dibenzo[b,d]pyran-6-one derivative; endocrine-disrupting; estrogen receptor
- and -estrogen receptors. Both urolithinsA and B showed estrogenic activity in a dose-dependent manner even at high concentrations (40M), without antiproliferative or toxic effects, whereas the other phytoestrogens inhibited cellproliferation at high concentrations. Overall, urolithins showed weaker estrogenic activity than theother phytoestrogens. However, both urolithins displayed slightly higher antiestrogenic activity(antagonized the growth promotion effect of 17--estradiol in a dose-dependent manner) than theother phytoestrogens. The IC50 values for the ER and ER binding assays were 0.4 and 0.75 Mfor urolithin A; 20 and 11 M for urolithin B; 3 and 0.02 for genistein; and 2.3 and 1 for daidzein,respectively; no binding was detected for resveratrol and enterolactone. Urolithins A and B enteredinto MCF-7 cells and were metabolized to yield mainly urolithin-sulfate derivatives. These results,together with previous studies regarding absorption and metabolism of dietary ellagitannins and ellagicacid in humans, suggest that the gut microflora metabolites urolithins are potential endocrine-disruptingmolecules, which could resemble other described "enterophytoestrogens" (microflora-derivedmetabolites with estrogenic/antiestrogenic activity). Further research is warranted to evaluate thepossible role of ellagitannins and ellagic acid as dietary "pro-phytoestrogens".Keywords: Breast cancer; phytoestrogen; hydroxy-6H-dibenzo[b,d]pyran-6-one derivative; endocrine-disrupting; estrogen receptor