title: Method for evaluating the potential of C labeled plant polyphenols to cross the blood-brain barrier using accelerator mass spectrometry.
abstract: Bioactive compounds in botanicals may be beneficial in preventing age-related neurodegenerative diseases, but for many compounds conventional methods may be inadequate to detect if these compounds cross the blood brain barrier or to track the pharmacokinetics in the brain. By combining a number of unique technologies it has been possible to utilize the power of AMS to study the pharmacokinetics of bioactive compounds in the brain at very low concentrations. (14)C-labeled compounds can be biosynthesized by plant cell suspension cultures co-incubated with radioisotopically-labeled sucrose and isolated and separated into a series of bioactive fractions.To study the pharmacokinetics and tissue distribution of (14)C labeled plant polyphenols, rats were implanted with jugular catheters, subcutaneous ultrafiltration probes and brain microdialysis probes. Labeled fractions were dosed orally. Interstitial fluid (ISF) and brain microdialysate samples were taken in tandem with blood samples. It was often possible to determine (14)C in blood and ISF with a β-counter. However, brain microdialysate samples (14)C levels on the order of 10(7) atoms/sample required AMS technology. The Brain Microdialysate(AUC)/Serum(AUC) ranged from .021- to .029, with the higher values for the glycoside fractions. By using AMS in combination with traditional methods, it is possible to study uptake by blood, distribution to ISF and determine the amount of a dose which can reach the brain and follow the pharmacokinetics in the brain.
authors.affiliation: Purdue University, Department of Foods and Nutrition, West Lafayette, IN, USA.
authors.forename: Elsa M
authors.initials: EM
authors.lastname: Janle
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Lila
authors.forename: Michael
authors.initials: M
authors.lastname: Grannan
authors.forename: Lauren
authors.initials: L
authors.lastname: Wood
authors.forename: Aine
authors.initials: A
authors.lastname: Higgins
authors.forename: Gad G
authors.initials: GG
authors.lastname: Yousef
authors.forename: Randy B
authors.initials: RB
authors.lastname: Rogers
authors.forename: Helen
authors.initials: H
authors.lastname: Kim
authors.forename: George S
authors.initials: GS
authors.lastname: Jackson
authors.forename: Connie M
authors.initials: CM
authors.lastname: Weaver