Location: Human Nutrition Research Center on Aging
Title: Xenobiotic metabolism and berry flavonoid transport across the blood brain barrier Authors
|Milbury, Paul -|
|Kalt, Wilhelmina -|
Submitted to: Journal of Agriculture and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 22, 2010
Publication Date: April 1, 2010
Citation: Milbury, P.E., Kalt, W. 2010. Xenobiotic metabolism and berry flavonoid transport across the blood brain barrier. Journal of Agriculture and Food Chemistry. 59(7):3950-3956. Interpretive Summary: Scientific evidence supports the hypothesis that berry flavonoids play a health beneficial role in preventing and reversing age-related neurological changes that occur during aging. Anthocyanins are bioactive flavonoids in berries suspected to be responsible for preventing cognitive impairment and protecting against neurodegenerative disorders. The exact biological mechanisms explaining anthocyanin actions in brain tissue can be determined only after scientists know how much anthocyanin reached the brain. Pigs were fed 2% whole freeze-dried, powdered blueberry in the diet for 8 weeks. Anthocyanin and their metabolites were measured in parts of the brain including the cortex, cerebellum, and midbrain and diencephalon using chromatography and mass spectroscopy. Anthocyanins and their metabolites were found in the brain at very low concentration, measuring only femptomoles per gram of fresh weight tissue at 18 hours after the pigs consumed their last meal. This time point is considered to be a fasting sample point and by this time anthocyanins had been removed from the blood by normal metabolism. This assures that the anthocyanins observed are actually in the brain tissue and not an artifact of contamination. While anthocyanin levels may have been higher closer to the meal, the observed levels nevertheless suggest that anthocyanins do not protect brain tissue primarily by quenching radicals. Glutathione, a small antioxidant made by the body is available in vastly higher quantities for this purpose. Rather, anthocyanins protect brain tissue by modifying signal transduction processes or the way cells communicate and/or gene expression in brain tissue and thus have a more profound effect on brain metabolism.
Technical Abstract: A compelling body of literature suggests berry phytochemicals play beneficial roles in reversing age-related cognitive impairment and protect against neurodegenerative disorders. Anthocyanins are bioactive phytochemicals in berries suspected to be responsible for some of these neuroprotective effects. The plausible mechanisms of anthocyanin bioactivity in brain tissue are dependent on their bioavailability to the brain. Pigs were fed 2% whole freeze-dried, powdered blueberry in the diet for 8 weeks. Anthocyanin and anthocyanin glucuronides were measured in the cortex, cerebellum, and midbrain and diencephalon by LC/MS/MS. Anthocyanins and their glucuronides were found in the range of femptomole/gram FW tissue at 18 hours postprandial, after anthocyanins had been removed from the blood by xenobiotic metabolism. Xenobiotic metabolism and anthocyanin interaction and transporter barriers to brain bioavailability are briefly discussed. The plausible mechanism of neuroprotective action of anthocyanins may be via modulation of signal transduction processes and/or gene expression in brain tissue rather than by direct antioxidant radical quenching.