The ability of anthocyanins to permeate the gastric mucosa can be suggested as a possible explanation of the fast kinetics of plasma appearance of anthocyanins in rats and humans. This paper presents an in vivo experiment aimed to prove the involvement of the stomach in the absorption of grape anthocyanins in rats. The required analytical selectivity and sensitivity was achieved by high-performance liquid chromatography, diode array detection and mass spectrometry. Malvidin 3-glucoside appeared in both portal and systemic plasma after only 6 min. The average concentrations measured in portal and systemic plasma were 0.650 þ 0.162 W WM and 0.234 þ 0.083 W WM (mean þ S.E.M.), respectively. ß

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Fruits and vegetables are rich in flavonoids, and ample epidemiological data show that diets rich in fruits and vegetables confer protection against cardiovascular, neurodegenerative and inflammatory diseases, and cancer. However, flavonoid bioavailability is reportedly very low in mammals and the molecular mechanisms of their action are still poorly known. This review focuses on membrane transport of flavonoids, a critical determinant of their bioavailability. Cellular influx and efflux transporters are reviewed for their involvement in the absorption of flavonoids from the gastro-intestinal tract and their subsequent tissue distribution. A focus on the mammalian bilirubin transporter bilitranslocase (TCDB 2.A.65.1.1) provides further insight into flavonoid bioavailability and its relationship with plasma bilirubin (an endogenous antioxidant). The general function of bilitranslocase as a flavonoid membrane transporter is further demonstrated by the occurrence of a plant homologue in organs (petals, berries) where flavonoid biosynthesis is most active. Bilitranslocase appears associated with sub-cellular membrane compartments and operates as a flavonoid membrane transporter.

Different polyphenol compounds are ingested when consuming a serving of fruits rich in polyphenols, spanning from one-phenol hydroxybenzoic acid to more complex polymeric compounds. Only a minor quantity of the polyphenols (5-10%) is absorbed. The remainder reaches the colon and is extensively metabolized by gut microbiota to low-molecular weight metabolites. Their subsequent tissue distribution is still undefined, although these microbial metabolites are currently believed to play a role in human health and disease states. To fill this knowledge gap, we performed a pharmacokinetics experiment in which a single bolus of 23 polyphenol microbial metabolites (total 2.7 μmol) was administered intravenously to rats to reliably reproduce a physiological postabsorption situation. Tissues and urine were collected shortly thereafter (15 s to 15 min) and were analyzed by UHPLC-MS/MS to quantitatively track these compounds. Remarkably, the brain was found to be a specific target organ for 10 of the 23 polyphenol metabolites injected, which significantly increased in the treated animals. In most cases, their appearance in the brain was biphasic, with an early wave at 2 min (4 compounds) and a second wave starting at 5 min; at 15 min, 9 compounds were still detectable. Most compounds were excreted into the urine. The concentrations in the brain of the treated animals were compared against those of the control group by Student's t test, with p-values < 0.1 considered to be statistically significant. These findings provide new perspectives for understanding the role of diet on brain chemistry. Our experimental approach has enabled us to obtain rich metabolomics information from a single experiment involving a limited number of animals.

Anthocyanins represent the main flavonoid pigments in red grape and wine, in red berries, and in many other fruits and vegetables and are widespread in the human diet. After ingestion, these complex, hydrophilic compounds quickly appear as intact molecules in the plasma. This study investigated their presence in the brain of anesthetized rats that received 8 mg/kg of body weight of a pure anthocyanin mixture extracted from Vitis vinifera grapes. The mixture was maintained in the stomach for 10 min. After this time, intact anthocyanins were detected by HPLC-DAD-MS not only in the plasma (176.4 +/- 50.5 ng/mL, mean +/- SEM) but also in the brain (192.2 +/- 57.5 ng/g). These results demonstrate for the first time that grape pigments can reach the mammalian brain within minutes from their introduction into the stomach.