NEUROPROTECTIVE ABILITIES OF NATURAL EXTRACTS AND PHYTONUTRIENTS IN HIPPOCAMPAL CELLS: POSSIBLE IMPACT IN BRAIN AGING ?





Rémi Quirion* & Stéphane Bastianetto

Douglas Hospital Research Centre
Department of Psychiatry and Pharmacology and Therapeutics
McGill University
6875 LaSalle Boulevard
Verdun Quebec
H4H 1R3 CANADA




Among various strategies that are envisioned to prevent or delay the onset of age-related neurological disorders, there is a growing number of studies suggesting that plant-derived extracts and phytonutrients have a beneficial impact on brain aging.
Considering that accumulation of b-amyloid (Ab) peptides and reactive oxygen species (ROS) plays a deleterious role in neurological disorders that occur during aging and in Alzheimer's disease (AD), we investigated the possible neuroprotective effects of various natural extracts and plant-derived polyphenolic constituents on cell death induced by either Ab peptides or oxidative stress in cultured cells of the hippocampus, an area involved in cognitive processes and severely affected in various neurodegenerative diseases including AD.
We found that the ginkgo biloba extract referred as EGb 761 was able to protect hippocampal neurons against toxic (necrotic, apoptotic, ROS accumulation) effects induced by Aß fragments (Aß25-35, Aß1-40, and Aß1-42), and these effects were attributable, at least in part, to its flavonoid polyphenols. Similar effects were observed with green tea- and grape seed-extracted ingredients known as derivatives of catechin.
Natural extracts such as EGb 761, green tea and grape seed extracts also protected hippocampal cells from toxicity induced by H2O2, a major peroxide possibly involved in mediating Aß toxicity, suggesting that purported neuroprotective effects are associated with antioxidant/free radical scavenging properties of their bio-active constituents.
Moreover, we found that an exposure of hippocampal cells to the free radical nitric oxide (NO) donors (sodium nitroprusside, SNP; 3-morpholinosydnonimine, SIN-1) resulted in both decrease in cell survival and increase in free radical accumulation that were inhibited by either EGb 761 or red wine-derived polyphenolic constituents such as the stilbene resveratrol, and the flavonols quercetin and (+)-catechin, mainly through their antioxidant activities. In addition, EGb 761 and quercetin, but neither resveratrol nor (+)-catechin, blocked the stimulatory effect of SNP on the activity of protein kinase C, an enzyme that is known to play a role in various neurodegenerative processes such as ischemic events, suggesting that their protective abilities also involve their inhibitory effect on NO-activated PKC activity.
Taken together, these results support the hypothesis that natural extracts may be useful in the treatment of brain amyloidosis associated with AD- and age-related cognitive symptoms. Moreover, these data raise the hypothesis that daily consumption of plant- and food-derived polyphenolic constituents that are present in human diet may have a positive impact in the incidence of age-related neuropathological diseases in which free radical accumulation likely plays a deleterious role.
This work was supported by the CIHR.




Key words: natural extracts;phytonutrients;amyloid peptides;oxidative stress;alzheimer's disease







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