Enhancement of flavonoid ability to cross the blood–brain barrier of rats by co-administration with α-tocopherol

Abstract

Vitamin E and polyphenols could exhibit a therapeutic role in the treatment of oxidative stress-induced neurodegenerative diseases. Therefore, their ability to cross the blood-brain barrier (BBB) represents an important issue to be explored by different diet combinations. In this study, we have evaluated the ability of α-tocopherol to support epigallocatechin-3-gallate (EGCG), quercetin and rutin to cross the BBB, following oral administration. Eighteen rats were fed a standard diet (C), a diet supplemented with α-tocopherol (A), with a mixture of EGCG, quercetin and rutin (P); or with a mixture of α-tocopherol and the three flavonoids (AP). Flavonoids and their conjugated derivatives were assayed in brain and plasma by HPLC-MS, whereas α-tocopherol was detected by RP-HPLC. The oxidative damage, due to the potential pro-oxidant activity of flavonoids, was evaluated by the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in hippocampal Cornus Ammonis, one of the most vulnerable sites in the brain. Our results indicate that α-tocopherol is able to promote quercetin transport across the BBB. The mixture of rutin and quercetin seems to favour the accumulation of quercetin and/or its conjugated derivatives in the brain. In contrast, α-tocopherol does not affect EGCG transport across the BBB. The densitometric analysis of 8-OHdG immunoreactivity does not reveal any difference of oxidative damage among the experimental groups. Our results suggest that α-tocopherol may promote quercetin transport across the BBB, leading to a significant increase of α-tocopherol and quercetin concentration in the brain.

Bioavailability of dietary polyphenols: Factors contributing to their clinical application in CNS diseases

“…However, there was no apparent difference in oxidative damage in the presence or absence of α-tocopherol (Ferri et al 2015). Table 1 lists the bioavailability of dietary polyphenols in the CNS.…”

Anti-amyloid Aggregation Activity of Natural Compounds: Implications for Alzheimer’s Drug Discovery

“…It should be noted that polar polyphenolic natural compounds such as 4, 5, 11, and 12 (Figs. 2 and 3) exhibit weak blood-brain barrier (BBB) penetration and can undergo metabolic changes in the gut, while some lipophilic compounds are capable of entering the brain and reaching levels higher than the physiological a The number of hydrogen bond donors and acceptors were calculated using the Discovery Studio program using CHARMm force field b Molecular volume was calculated using the Discovery Studio (BIOVIA/Accelrys Inc) program energy minimization c AlogP was calculated using the Discovery Studio program concentration of soluble Aβ in the brain [60,[116][117][118]. Thus, the development of new compounds with superior in vivo metabolic stability and BBB penetration is critical.…”

Flavonoids and Diarylheptanoids: Neuroprotective Activities of Phytochemicals

“…This test mimics oxidative stress that is attributed to the development of neurodegenerative disorders [18]. alpha-tocopherol as verified by the increase in the presence of flavonoid derivatives in the brain and plasma as detected by high performance liquid chromatography mass spectrometry [14]. The use of rutin on rats in 100 mg/kg/day dosage for five weeks suggests an application for rutin in the treatment of the neurodegenerative eye disease diabetic retinopathy since rutin promotes nerve growth [36].…”

“…The neuroprotective effects of flavonoids and diarylheptanoids were tested using H202 and glutamate stressed cell lines [18,14,[25][26][27][28][29][30][31]. This test mimics oxidative stress that is attributed to the development of neurodegenerative disorders [18].…”