M. A. Núñez-Sánchez and R. García-Villalba contributed equally to the work.
Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients
Article first published online: 16 FEB 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 6, pages 1199–1211, June 2014
How to Cite
Nuñez-Sánchez, M. A., García-Villalba, R., Monedero-Saiz, T., García-Talavera, N. V., Gómez-Sánchez, M. B., Sánchez-Álvarez, C., García-Albert, A. M., Rodríguez-Gil, F. J., Ruiz-Marín, M., Pastor-Quirante, F. A., Martínez-Díaz, F., Yáñez-Gascón, M. J., González-Sarrías, A., Tomás-Barberán, F. A. and Espín, J. C. (2014), Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients. Mol. Nutr. Food Res., 58: 1199–1211. doi: 10.1002/mnfr.201300931
- Issue published online: 5 JUN 2014
- Article first published online: 16 FEB 2014
- Manuscript Accepted: 16 JAN 2014
- Manuscript Revised: 14 JAN 2014
- Manuscript Received: 10 DEC 2013
- MINECO, Spain
- Clinical trial;
- Colon cancer;
- Ellagic acid;
Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from colorectal cancer (CRC) patients after pomegranate extract (PE) intake.
Methods and results
CRC patients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE-1) and high (PE-2) punicalagin:EA ratio were administered. Twenty-three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC-ESI-QTOF-MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 ± 367 ng/g) was found in NT after consumption of PE-1 and the lowest concentration (42.4 ± 10.2 ng/g) in MT with PE-2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE-2) hampered urolithins formation.
Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.