title: Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, Campus de Espinardo, Murcia, Spain.
authors: María A
authors: MA
authors: Nuñez-Sánchez
authors: Rocío
authors: R
authors: García-Villalba
authors: Tamara
authors: T
authors: Monedero-Saiz
authors: Noelia V
authors: NV
authors: García-Talavera
authors: María B
authors: MB
authors: Gómez-Sánchez
authors: Carmen
authors: C
authors: Sánchez-Álvarez
authors: Ana M
authors: AM
authors: García-Albert
authors: Francisco J
authors: FJ
authors: Rodríguez-Gil
authors: Miguel
authors: M
authors: Ruiz-Marín
authors: Francisco A
authors: FA
authors: Pastor-Quirante
authors: Francisco
authors: F
authors: Martínez-Díaz
authors: María J
authors: MJ
authors: Yáñez-Gascón
authors: Antonio
authors: A
authors: González-Sarrías
authors: Francisco A
authors: FA
authors: Tomás-Barberán
authors: Juan C
authors: JC
authors: Espín
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002853:Chromatography, Liquid; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003374:Coumarins / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004610:Ellagic Acid / Q000378:metabolism; D005260:Female; D006801:Humans; D047348:Hydrolyzable Tannins / Q000097:blood / Q000652:urine; D057230:Limit of Detection; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: D003374:Coumarins; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D059808:Polyphenols; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D004610:Ellagic Acid; C115642:punicalagin
keywords: Clinical trial; Colon cancer; Ellagic acid; Pomegranate; Urolithins