Pharmacokinetics and tissue distribution of 14C-labeled grape polyphenols in the periphery and the central nervous system following oral administration.
Grape polyphenols confer potential health benefits, including prevention of neurodegenerative diseases. To determine the absorption and tissue distribution of the complex grape polyphenol mixture, (14)C-labeled polyphenols were biosynthesized by grape cell suspension cultures, during co-incubation with radioisotopically labeled sucrose, and fractionated into polyphenolic subfractions. The pharmacokinetics and distribution of grape polyphenols into blood, brain, and peripheral interstitial fluid were determined by tracking the (14)C label. The blood peak (14)C concentration of the fractions ranged from 15 minutes to 4 hours. Absorption and tissue distribution varied greatly between fractions. Concentrations in interstitial fluid were lower than in blood. The amount of residual label in the brain at 24 hours ranged from 0.1% to 1.7% of the dose, depending on the fraction. (14)C label found in the brain tissue and brain microdialysate indicated that grape polyphenols or their metabolites are able to cross the blood-brain barrier. Using (14)C-labeled plant polyphenols it is possible to track the compounds or their metabolic products into any tissue and determine distribution patterns in spite of low concentrations. A central question regarding the potential role of dietary polyphenolics in neurodegenerative research is whether they are bioavailable in the brain. Our observations indicate that some grape-derived polyphenolics do reach the brain, which suggests their potential value for applications in neurodegenerative disorders.
Janle
Elsa M
EM
Department of Foods and Nutrition, Purdue University, West Lafayette, Indiana 47907-2059, USA. janle@purdue.edu
Lila
Mary Ann
MA
Grannan
Michael
M
Wood
Lauren
L
Higgins
Aine
A
Yousef
Gad G
GG
Rogers
Randy B
RB
Kim
Helen
H
Jackson
George S
GS
Ho
Lap
L
Weaver
Connie M
CM
D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes / Q000032:analysis / Q000493:pharmacokinetics; D002490:Central Nervous System / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D045604:Extracellular Fluid / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D010636:Phenols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D027843:Vitis / Q000737:chemistry*
D002250:Carbon Radioisotopes; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols