Pharmacokinetics and Tissue Distribution of¹⁴C-Labeled Grape Polyphenols in the Periphery and the Central Nervous System Following Oral Administration

Abstract

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.

Effect of aronia melanocarpa fruit juice on reserpine-induced hypokinesia and oxydative stress in rats

“…The main AMFJ anthocyanins are glycosides of cyanidin. Recent studies have shown that polyphenols from berries can cross the blood-brain barrier (1,14,19) and do accumulate in the brain following long-term consumption (24).…”

Antioxidant Plant Polyphenols and Cognitive Disorders

“…However, these signals were lower than those in corresponding samples of blood. The amount of residual label in the brain did not exceeded 1.7 % of the dose, and the radioactivity was spread homogenously over all the brain structures (Janle et al 2010 ).…”

“…Single oral administration of 14 C-labeled grape polyphenols preparation in rats resulted in the appearance of radioactivity in cerebral interstitial fl uid sampled with microdialysis probes from hippocampus and also in brain slices obtained at 24-h postdose (Janle et al 2010 ). Maximal signals for labeled catechin/epicatechin (monomers, oligomers) peonidins, cyanidins, and cyanidin glycosides occurred in cerebral fl uid sampled between 0.75 and 1.5 h after grape polyphenols ingestion.…”

Therapeutic targets of brain insulin resistance in sporadic Alzheimer s disease

“…Grape seed extracts also contain resveratrol, and therefore provide neuroprotection (269,270). Pharmacokinetic studies have affirmed that grape seed polyphenols abundantly distribute in the brain (271). The neuroprotective actions of resveratrol are mediated by enhancement of glutathione free radical scavenger activity (272,273), and reduction in AβPP-Aβ levels (274) due to increased clearance via the proteasome (275) or autophagy and lysosomal degradation (276).…”