Administration Time Significantly Affects Plasma Bioavailability of Grape Seed Proanthocyanidins Extract in Healthy and Obese Fischer 344 Rats

Abstract

Scope: Phenolic compounds are bioactive molecules that are associated with several health benefits. Metabolization and absorption are the main determinants of their bioavailability and bioactivity. Thus, the study of the factors that modulate these processes, such as sex or diet is essential. Recently, it has been shown that biological rhythms may also play a key role. Hence, the aim of this study is to evaluate if the bioavailability of a grape proanthocyanidin extract (GSPE) is affected by the administration time in an animal model of metabolic syndrome (MetS). Methods and Results: Female and male Fischer 344 rats are fed either a standard or a cafeteria diet (CAF) for 9 weeks, and an oral dose of GSPE (25 mg kg−1) is daily administered either at 8:00 am (zeitgeber time (ZT)-0) or at 8:00 pm (ZT-12) during the last 4 weeks. Plasma phenolic compounds are then quantified by liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Phase-II and gut microbiota-derived phenolic metabolites are affected by ZT in all conditions or only in obese rats, respectively. CAF feeding affected the bioavailability of phenolic acids and free flavan-3-ols. Differences due to sex are also observed. Conclusion: These findings demonstrate that ZT, diet, and sex are key factors influencing phenolic compounds bioavailability.