NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins

J Nutr Biochem. 2016 Aug:34:136-45. doi: 10.1016/j.jnutbio.2016.05.007. Epub 2016 May 27.


A (1)H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using (1)H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D (1)H-(13)C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and α-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, α-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake.

Keywords: Cranberries; Metabolomics; Multivariate analyses; NMR; Procyanidins.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Animals
  • Anti-Infective Agents, Urinary / administration & dosage*
  • Anti-Infective Agents, Urinary / metabolism
  • Biomarkers / urine
  • Dietary Supplements*
  • Discriminant Analysis
  • Female
  • Freeze Drying
  • Fruit / chemistry*
  • Hippurates / urine
  • Lactic Acid / urine
  • Magnetic Resonance Spectroscopy
  • Malus / chemistry
  • Metabolomics / methods*
  • Plant Extracts / administration & dosage*
  • Plant Extracts / chemistry
  • Plant Extracts / metabolism
  • Principal Component Analysis
  • Proanthocyanidins / administration & dosage*
  • Proanthocyanidins / analysis
  • Proanthocyanidins / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Renal Elimination
  • Succinic Acid / urine
  • Vaccinium macrocarpon / chemistry*


  • Anti-Infective Agents, Urinary
  • Biomarkers
  • Hippurates
  • Plant Extracts
  • Proanthocyanidins
  • Lactic Acid
  • Succinic Acid
  • hippuric acid