The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats

Abstract

Rats were fed ag rape seed extract (GSE) containing ( þ )-catechin,( 2 )-epicatechin and dimers, trimers, tetramers and polymeric procyanidins. Liver, kidney, brain and gastrointestinal (GI) tract together with plasma, urine and faeces were collected over a24h period and their flavan-3-ol content was analysed by HPLC with tandem mass spectrometry and diode array detection. Small amounts of the GSE flavan-3-ols moved out of the stomach and into the duodenum/jejunum, and to ag reater extent the ileum 1h after ingestion, and into the caecum after 2h with relatively small amounts being detected in the colon after 3h.T he GI tract contained the parent GSE flavan-3-ols and procyanidins with only trace amounts of metabolites and there were no indications that proanthocyanidins were depolymerised in the GI tract releasing monomeric flavan-3-ols.Plasma contained exclusively catechin glucuronidesand methylated glucuronide metabolites which were also detected in the liver and kidneys. These metabolites were also present in urine together with sulphated metabolites and low amounts of the procyanidin dimers B 1 ,B 2 ,B 3 and B 4 as well as the trimer C 2 and an unknown GSE trimer. The amounts of ( þ )-catechin and ( 2 )-epicatechin metabolitesexcreted in urine relative to the quantity of the monomers ingested were 27 and 36 %, respectively, after 24 h. This is similar to the levels of urinary excretion reported to occur by other investigators after feeding ( 2 )-epicatechin to rats and provides further, albeit indirect, evidence that the procyanidinoligomers in the GSE were not depolymerised to monomers to any extent after ingestion. No convincing analytical data were obtained for the presence of flavan-3-ol metabolites in the brain.

Effects of Herbal Supplements on Drug Glucuronidation. Review of Clinical, Animal, andIn VitroStudies

“…Resveratrol is also a substrate for UGT1A1 and UGT1A9 enzymes, but no information is available on its potential to modulate UGT enzymes [54,55]. In rats, catechin glucuronides were the primary existing form of catechins in plasma following oral grape seed extract administration [80]. Taken together, grape seed extract is rich in phytochemicals that are substrates for UGT enzymes.…”

Bioavailability of procyanidin dimers and trimers and matrix food effects in in vitro and in vivo models

“…PC belong to the group of flavonoids, and are phenolic compounds mainly formed of (þ)-catechin and (2 )-epicatechin units with C 4 -C 8 and/or C 4 -C 6 bonds. PC are formed from the condensation of monomeric units, between two and five units for oligomers and over five units for polymers (1) .Grape seed procyanidin extracts (GSPE) have shown several bioactivities. They improve antioxidant cell defences (2) and the plasma lipid profile (3,4) , limit adipogenesis (5) and function as insulinomimetic (6) and anti-inflammatory (7) agents.…”

“…PC belong to the group of flavonoids, and are phenolic compounds mainly formed of (þ)-catechin and (2 )-epicatechin units with C 4 -C 8 and/or C 4 -C 6 bonds. PC are formed from the condensation of monomeric units, between two and five units for oligomers and over five units for polymers (1) .…”

In Vivo Bioavailability, Absorption, Excretion, and Pharmacokinetics of [14C]Procyanidin B2 in Male Rats

“…Later studies in animals, using liquid chromatography/electrospray ionization/mass spectrometry analyses, reported the presence, after enzymatic hydrolysis, of unconjugated procyanidin dimers, including B1, B2, B3, B4, and B5, in various tissues including plasma and urine after feeding large doses of proanthocyanidin extracts or proanthocyanidin-rich seeds (Baba et al, 2002;Tsang et al, 2005;Shoji et al, 2006). Likewise, human studies have detected unconjugated procyanidin B1, B2, and B5 in plasma and serum within 30 min of consumption of the test material (Holt et al, 2002;Sano et al, 2003).…”