Plasma Levels and Distribution of Flavonoids in Rat Brain after Single and Repeated Doses of StandardizedGinkgo bilobaExtract EGb 761®

Abstract

It is undisputed that terpene lactones and flavonoid glycosides of Ginkgo biloba are responsible for most of the extracts (e.g., EGb 761®) pharmacological actions. This investigation focused on the pharmacokinetic and the ability of the flavonoid constituents to cross the blood-brain barrier in rats, after single (600 mg/kg) or repeated (8 days, 100, or 600 mg/kg) oral administration of EGb 761®, and their distribution in different areas of the brain. For this purpose, we developed an HPLC-fluorescence method for the determination of the Ginkgo flavonoid metabolites (quercetin, kaempferol, and isorhamnetin derivatives) in the brain and plasma. A single dose of 600 mg/kg EGb 761® resulted in maximum plasma concentrations of 176, 341, and 183 ng/mL for quercetin, kaempferol, and isorhamnetin/tamarixetin, respectively and in maximum brain concentrations of 291 ng/g protein for kaempferol and 161 ng/g protein for isorhamnetin/tamarixetin. In comparison, the repeated administration of the same dose for 8 days led to an approximate 4.5-fold increase in the plasma concentration for quercetin, 11.5-fold increase for kaempferol, and 10-fold increase for isorhamnetin/tamarixetin. In the brain, an approximate 2-fold increase was observed for kaempferol and isorhamnetin/tamarixetin. About 90% of the determined flavonoids were distributed in the hippocampus, frontal cortex, striatum, and cerebellum, which together represent only 38% of the whole brain.

Effects of Quercetin on Human α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor-Mediated Ion Currents

“…24) However, it appears that the measured concentrations of flavonoids including qurecetin in rat brain and plasma after oral administration of standardized Gingko bilboa (EGb 761), which is rich in flavonoids, was in the range of nM. 41) The concentration is much less than those of flavonoids including quercetin exhibiting various in vitro neuropharmacological actions including the present study. 15,16) Therefore, we must be careful to explain the beneficial effects of flavonoids including quercetin in nervous systems.…”

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).…”

Simultaneous Determination of Flavonols and Terpene Lactones in Beagle Dog Plasma by Ultra-Performance Liquid Chromatography-Tandem - Mass Spectrometry: 1. Method Development

“…FDA suggested that botanical drug products should be investigated with regard to blood levels of known representative markers, active constituents, and major chemical constituents. The pharmacokinetic studies of G. biloba and its preparations were mostly implemented in rats, which most only for flavonols or lactones of single preparation [13][14][15][16][17]. In this paper, a UPLC-ESI-MS/MS method for simultaneous determination of three flavonoids (KMF, QCT, and ISR) and four lactones (GA, GB, GC, and BB) in beagle dog plasma was described for the first time.…”