Bioavailability of Gallic Acid and Catechins from Grape Seed Polyphenol Extract is Improved by Repeated Dosing in Rats: Implications for Treatment in Alzheimer's Disease

Abstract

The present study explored the bioavailability and brain deposition of a grape seed polyphenolic extract (GSPE) previously found to attenuate cognitive deterioration in a mouse model of Alzheimer's disease (AD). Plasma pharmacokinetic response of major GSPE phenolic components was measured following intragastric gavage of 50, 100, and 150 mg GSPE per kg body weight. Liquid chromatography-mass spectrometry (LC-MS) analysis identified gallic acid (GA), catechin (C), and epicatechin (EC) in plasma of rats gavaged acutely with GSPE. Additionally, 4-methylgallic acid (4-OMeGA), 3'-methylcatechin (3'-OMeC), and 3'-methylepicatechin (3'-OMeEC) were identified as circulating metabolites of GSPE phenolic constituents. Cmax for individual GSPE constituents and their metabolites increased in a dose-dependent fashion (with increasing GSPE oral dose). Repeated daily exposure to GSPE was found to significantly increase bioavailability (defined as plasma AUC0-8h) of GA, C, and EC by 198, 253, and 282% relative to animals receiving only a single acute GSPE dose. EC and C were not detectable in brain tissues of rats receiving a single GSPE dose but reached levels of 290.7 +/-45.9 and 576.7 +/- 227.7 pg/g in brain tissues from rats administered GSPE for 10 days. This study suggests that brain deposition of GA, C, and EC is affected by repeated dosing of GSPE.

Paired Helical Filaments from Alzheimer Disease Brain Induce Intracellular Accumulation of Tau Protein in Aggresomes

“…Grape-derived bioactive GSE preparations comprising proanthocyanidins have been demonstrated to exert a wide scope of neuroprotective biological activities in animal models of tauopathy and neurodegeneration (33)(34)(35)(36)65). More complex proanthocyanidins, however, including dimers, trimers, and oligomers have a reduced bioavailability in the rat brain when compared with monomers (66). Results of the present studies indicate that such a bioavailable monomeric GSE-enriched fraction may interfere with the formation of GFP-Tau aggregates.…”

Tannic Acid Is a Natural β-Secretase Inhibitor That Prevents Cognitive Impairment and Mitigates Alzheimer-like Pathology in Transgenic Mice

“…In particular, oral administration of gallic acid led to intestinal absorption over a period of ϳ60 min in rodents (69), which equated to 76 min in humans (70). Flavonoids including gallate have also been shown to cross into the brain in rodents (68,71,72). Thus, the gallate moiety is a likely candidate for mediating the bioactivity of TA in our system; yet, future study is warranted to characterize which chemical structure in TA plays a pivotal role on mitigating A␤ pathology.…”

The Gallic Acid–Phospholipid Complex Improved the Antioxidant Potential of Gallic Acid by Enhancing Its Bioavailability

“…In one experiment conducted in healthy human volunteers, the maximum concentration of GA in plasma was 1.83±0.16 μmol/L after intake of 50 mg GA (12). In another experiment, after oral administration of 50, 100, and 150 mg/kg grape seed extract containing 91 mg GA/g of extract in male Sprague-Dawley rats, the C max of GA was 309.8 ±102.6, 239.6±39.2, and 323.4±76.9 ng/mL (13). In the present study, the C max of GA was 2.5±0.18 μg/mL after 150 mg/kg oral dose of pure GA, which is quite comparable to previous works.…”

“…Despite these health benefits, the usage of GA is restricted due to its poor absorption, low bioavailability, and rapid elimination from the body studied both in human and animal (12,13). GA metabolizes rapidly to its major metabolite 4-Omethylgallic acid and pyrogallol which are converted to pyrogallol-1-O-β-D-glucuronide, 4-O-methylgallic acid-3-O-sulfate, 2-O-methylpyrogallol-1-O-β-D-glucuronide, 2-Omethylpyrogallol, and 4-O-methylgallic acid (14)(15)(16)(17).…”