Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients

María A. Nuñez-Sánchez, Rocío García-Villalba, Tamara Monedero-Saiz, Noelia V. García-Talavera, María B. Gómez-Sánchez, Carmen Sánchez-Álvarez, Ana M. García-Albert, Francisco J. Rodríguez-Gil, Miguel Ruiz-Marín, Francisco A. Pastor-Quirante, Francisco Martínez-Díaz, María J. Yáñez-Gascón, Pomegranate ImageAntonio González-Sarrías, Francisco A. Tomás-Barberán and Juan C. Espín

Maria Nunez-Sanchez and colleagues from Quality, Safety and Bioactivity of Plant Foods (Campus de Espinardo, ES) and the Nutrition, Digestion, Surgery and Anatomical Pathology Services (Hospital Reina Sofia, Murcia, ES) found that colorectal cancer cells taken from patients who had consumed pomegranate extract (PE) contained bioactive polyphenols, such as ellagic acid (EA) and urolithins.

EA is a polyphenol that is known to lower blood pressure and delay the growth of cancer cells whilst urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and EA. However, it was not known if these compounds reach colon tissue following oral intake of PE.

This study found that cells taken from patients who had consumed PE contained free (EA), five EA conjugates, gallic acid and 12 urolithins. However, individual and total metabolite levels of these derivatives were higher in healthy tissue compared to tumour cells, regardless of the amounts of PE consumed. Further studies are required to better understand the potentially beneficial biological activity of EA and its derivatives, such as urolithins, if a health claim for PE in the prevention or management of colorectal cancer is to be made. One of the first stages in this process was to determine if these metabolites are present in colorectal tissues following oral consumption of PE.

CRC patients (n = 52) were assigned to two groups, either a control PE-consumer (900 mg/day for 15 days) group prior to surgical resection. PEs with low (PE-1) and high (PE-2) punicalagin:EA ratios were consumed by the second group of patients. Urolithins were detected in urine, blood plasma, and normal or malignant tissues using UPLC-ESI-QTOF-MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole time-of-flight; mass spectrometry).

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  1. Urolithin A and isourolithin A were the main urolithins produced by patients with urolithin A (54%) and isourolithin A (46%) phenotypes
  2. High punicalagin content (PE-2) hampered urolithins formation
  3. Free ellagic acid (EA), five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues from patients consuming PE