Browsing by Subject "Ellagitannins"
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- PublicationRestrictedGene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial(Elsevier, 2017-01-27) Nuñez-Sánchez, María A.; González Sarrías, Antonio; García Villalba, Rocío; Monedero Saiz, Tamara; García Talavera, Noelia V.; Gómez Sánchez, María B.; Sánchez Álvarez, Carmen; García Albert, Ana M.; Rodríguez Gil, Francisco J.; Ruiz Marín, Miguel; Pastor Quirante, Francisco A.; Martínez Díaz, Francisco; Tomás Barberán, Francisco A.; Espín, Juan Carlos; García Conesa, María Teresa; Oftalmología, Optometría, Otorrinolaringología y Anatomía PatológicaThe clinical evidence of dietary polyphenols as colorectal cancer (CRC) chemopreventive compounds is very weak. Verification in humans of tissue-specific molecular regulation by the intake of polyphenols requires complex clinical trials that allow for the procurement of sufficient pre- and postsupplementation tissue samples. Ellagitannins (ETs), ellagic acid (EA) and their gut microbiota-derived metabolites, the urolithins, modify gene expression in colon normal and cancer cultured cells. We conducted here the first clinical trial with 35 CRC patients daily supplemented with 900 mg of an ET-containing pomegranate extract (PE) and evaluated the expression of various CRC-related genes in normal and cancerous colon tissues before (biopsies) and after (surgical specimens) 5–35 days of supplementation. Tissues were also obtained from 10 control patients (no supplementation) that confirmed a large, gene- and tissue-specific interindividual variability and impact of the experimental protocol on gene expression, with some genes induced (MYC, CD44, CDKN1A, CTNNB1), some repressed (CASP3) and others not affected (KRAS). Despite these issues, the consumption of the PE was significantly associated with a counterbalance effect in the expression of CD44, CTNNB1, CDKN1A, EGFR and TYMs, suggesting that the intake of this PE modulated the impact of the protocol on gene expression in a gene- and tissue-specific manner. These effects were not associated with the individuals' capacity to produce specific urolithins (i.e., metabotypes) or the levels of urolithins and EA in the colon tissues and did not reproduce in vitro effects evidencing the difficulty of demonstrating in vivo the in vitro results.
- PublicationRestrictedOccurrence of urolithins, gut microbiota ellagic acid metabolites and proliferation markers expression response in the human prostate gland upon consumption of walnuts and pomegranate juice(Wiley, Wiley-VCH Verlag, 2010-03) Gonzalez-Sarrias, Antonio; Giménez Bastida, Juan A.; García-Conesa, María T.; Gómez-Sánchez, Maria B.; García Talavera, Noelia V.; Gil-Izquierdo, Ángel; Sánchez-Álvarez, Carmen; Fontana-Compiano, Luis O.; Morga-Egea, Juan P.; Pastor-Quirante, Francisco A.; Martinez Diaz, Francisco; Tomás-Barberan, Francisco A.; Espín, Juan Carlos; Oftalmología, Optometría, Otorrinolaringología y Anatomía PatológicaEpidemiology supports the important role of nutrition in prostate cancer (PCa) prevention. Pomegranate juice (PJ) exerts protective effects against PCa, mainly attributed to PJ ellagitannins (ETs). Our aim was to assess whether ETs or their metabolites ellagic acid and urolithins reach the human prostate upon consumption of ET-rich foods and to evaluate the effect on the expression of three proliferation biomarkers. Sixty-three patients with BPH or PCa were divided into controls and consumers of walnuts (35 g walnuts/day) or pomegranate (200 mL PJ/day) for 3 days before surgery. Independently of the ETs source, the main metabolite detected was urolithin A glucuronide, (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide) (up to 2 ng/g) together with the traces of urolithin B glucuronide, (3-hydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide) and dimethyl ellagic acid. The small number of prostates containing metabolites was likely caused by clearance of the compounds during the fasting. This was corroborated in a parallel rat study and thus the presence of higher quantities of metabolites at earlier time points cannot be discarded. No apparent changes in the expression of CDKN1A, MKi-67 or c-Myc were found after consumption of the walnuts or PJ. Our results suggest that urolithin glucuronides and dimethyl ellagic acid may be the molecules responsible for the beneficial effects of PJ against PCa.