Urinary excretion of 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone, a ring-fission metabolite of (-)-epicatechin, in rats and its in vitro antioxidant activity

J Agric Food Chem. 2003 Nov 5;51(23):6893-8. doi: 10.1021/jf034578e.


There is great interest in the nutritional potential of (-)-epicatechin, a common polyphenolic constituent of many foods and beverages, because of its potent antioxidant capacity. To better evaluate the biological role of (-)-epicatechin, we studied the urinary excretion of 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone, a ring-fission metabolite of (-)-epicatechin by intestinal microflora, in rats as well as its antioxidant activity in vitro. The method for measuring the urinary levels of (-)-epicatechin and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone was based on the enzymatic hydrolysis of beta-glucuronidase and sulfatase, and was subsequently determined by HPLC coupled to an electrochemical detector. Following administration of (-)-epicatechin at doses of 0, 20, 40, and 80 mumol per rat, (-)-epicatechin and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone were excreted into the urine within 24 h in a dose-dependent manner. Urinary 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone was mostly in the conjugated form, with a higher ratio of conjugation than (-)-epicatechin. We assessed the relative antioxidant potentials for scavenging radicals in the aqueous phase as expressed in the Trolox equivalent antioxidant capacity (TEAC). The results demonstrated that the degradation of (-)-epicatechin into 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone attenuated the antioxidant ability of the former. However, 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone showed stronger antioxidant activity than l-ascorbic acid. These results led us to suppose that 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone, a microbial metabolite of (-)-epicatechin, circulating in the body may also at least be biologically active in terms of contributing to its combined antioxidant effect.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology
  • Catechin / metabolism*
  • Catechin / urine
  • Chromans / chemistry
  • Chromatography, High Pressure Liquid
  • Lactones / pharmacology*
  • Lactones / urine*
  • Male
  • Rats
  • Rats, Wistar


  • (-)-5-(3',4'-dihydroxyphenyl)-valerolactone
  • Antioxidants
  • Chromans
  • Lactones
  • Catechin
  • Ascorbic Acid
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid