Profiling Vaccinium macrocarpon components and metabolites in human urine and the urine ex-vivo effect on Candida albicans adhesion and biofilm-formation

Biochem Pharmacol. 2020 Mar:173:113726. doi: 10.1016/j.bcp.2019.113726. Epub 2019 Nov 26.

Abstract

The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran®). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran® were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran™ Phytosome™, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone was found effective thus confirming the ex-vivo results.

Keywords: Candida albicans; Cranberry; Mass spectrometry; UTIs; Urine metabolites; Vaccinium macrocarpon.

MeSH terms

  • Adult
  • Anthocyanins / urine
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Candida albicans / drug effects*
  • Candida albicans / physiology
  • Chromatography, High Pressure Liquid / methods
  • Female
  • Flavonoids / urine
  • Humans
  • Hydroxybenzoates / urine
  • Lactones / chemistry
  • Lactones / pharmacology*
  • Lactones / urine
  • Mass Spectrometry / methods
  • Pentanoic Acids / chemistry
  • Pentanoic Acids / pharmacology*
  • Pentanoic Acids / urine
  • Plant Extracts / administration & dosage
  • Plant Extracts / metabolism
  • Plant Extracts / urine*
  • Polyphenols / classification
  • Polyphenols / urine
  • Vaccinium macrocarpon / chemistry*
  • Young Adult

Substances

  • Anthocyanins
  • Flavonoids
  • Hydroxybenzoates
  • Lactones
  • Pentanoic Acids
  • Plant Extracts
  • Polyphenols
  • n-pentanoic acid
  • phenolic acid
  • gamma-valerolactone
  • 3-hydroxyflavone