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SUMMARYIncreasing evidence suggests that depression may be both a cause and consequence of neurological disorders such as Alzheimer's disease (AD), and that antidepressants could provide an alternative strategy to current AD therapies. Association of side effect and herbal-drug interaction with conventional antidepressant and St. John's wort warrant investigating new antidepressant drugs. Antidepressant effects of ginkgo biloba extract (EGb 761) have been demonstrated in animal models of depression and in human volunteers. We report here that ginkgo flavonols quercetin and kaempferol stimulates depression-related signaling pathways involving brain-derived neurotrophic factor BDNF/phosphorylation of cyclic AMP response element binding protein CREB/postsynaptic density proteins PSD95, and reduces amyloid-β peptide (Aβ) in neurons isolated from double transgenic AD mouse (TgAPPswe/PS1e9). In addition, enhanced BDNF expression and reduction of Aβ oligomers was confirmed in hippocampus of the double transgenic mice administered with flavonol, which correlates with cognitive improvement behaviors in these mice. The present results suggest that stimulating BDNF and reducing Aβ toxicity by natural flavonols provide a therapeutic implication for treatment of AD.

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