Biology Reference
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direct contact in vivo with food ETs should be considered with caution.
This is for example the case of studies testing activity of ETs on liver or
breast cancer cell lines. In cultured cells representing systemic tissues
and organs, we should be best evaluating the bioactivity of the actual
metabolites circulating in plasma (urolithins and their glucuronic acid
conjugates) and at the in vivo concentrations reached in plasma (mean
values about 1-5 μM) and/or in tissues (detectable but generally below
the quantification limit). ETs and EA are more relevant in terms of
bioactivity at the gastrointestinal tract, where they are present at
significant concentrations. Both in vitro and in vivo studies show the
potential of these polyphenols as chemopreventive agents in several
types of cancer.
The metabolic transformation of ETs into urolithins A and B is a
widespread phenomenon in nature. These urolithin metabolites have
been previously reported to be present in the faeces of the squirrel
Trogopterus xanthippes and their hyaluronidase inhibitory activity was
also demonstrated (Jeong et al. , 2000). These metabolites have also been
isolated from kidney stones in cattle suffering from the “clover stone”
disease, which is most likely associated with a large and chronic intake
of a clover species ( Trifolium subterraneum ) (Pope, 1964), probably rich
in ETs. Urolithins A and B have also been isolated from beaver
excretions and as such are constituents of Castoreum (Lederer, 1949).
Castoreum is a urine-based fluid from castor sacs and/or anal-gland
secretion (Rosell et al. , 2000).
Apart from the hyaluronidase inhibitory activity (Jeong et al. , 2000),
no other biological activity has been yet attributed to the microbial
metabolites urolithins. However, it is anticipated that these gut
microflora metabolites are potential endocrine-disrupting molecules,
which could resemble other described “enterophytoestrogens”
(microflora-derived metabolites with estrogenic/antiestrogenic activity).
They may have potential estrogenic/antiestrogenic effects in the range of
that is reported for other well-known estrogenic compounds such as
enterolactone, resveratrol, genistein or daidzein (Larrosa et al. , 2006b).
Further research is warranted to evaluate the possible role of ETs and EA
as dietary “pro-phytoestrogens”.
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