Effect of a short- and long-term treatment with Ginkgo biloba extract on Amyloid Precursor Protein Levels in a transgenic mouse model relevant to Alzheimer's disease

Institute of Animal Nutrition and Physiology, Christian-Albrechts-University of Kiel, Hermann-Rodewald-Strasse 9, 24098 Kiel, Germany.
Archives of Biochemistry and Biophysics (Impact Factor: 3.02). 11/2008; 481(2):177-82. DOI: 10.1016/
Source: PubMed


Several clinical trials have reported beneficial effects of the Ginkgo biloba extract EGb761 in the prevention and therapy of cognitive disorders including Alzheimer's disease (AD). The aim of the present long-term feeding trial was to study the impact of dietary EGb761 on Amyloid precursor protein (APP) metabolism in mice transgenic for human APP (Tg2576). Tg2576 mice were fed diets with and without EGb761 (300 mg/kg diet) for 1 and 16 months, respectively. Long-term treatment (16 months) with EGb761 significantly lowered human APP protein levels by approximately 50% as compared to controls in the cortex but not in the hippocampus. However, APP levels were not affected by EGb761 in young mice. Current data indicate that APP seems to be an important molecular target of EGb761 in relation to the duration of the Ginkgo biloba treatment and/or the age of the animals. Potential neuroprotective properties of EGb761 may be, at least partly, related to its APP lowering activity.

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Available from: Gerald Rimbach, Jan 30, 2015
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    • "It showed that longterm treatment with the extract significantly lowered APP levels by more than half in cortex but not hippocampus when compared to controls. APP levels, however, were not affected in young mice treated for one month [173]. While the soluble Aβ load and plaque burden were not changed, Tg2576 mice receiving six months of oral treatment with 70mg/kg of EGb 761 daily were able to retain spatial memory to a similar level as wild type mice whereas untreated Tg2576 mice showed spatial learning impairments [174]. "
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    ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Bio- and histochemical evidence suggests a pivotal role of central and peripheral inflammation in its aetiopathology, linked to the production of free radicals. Numerous epidemiological studies support that the long-term use of non-steroidal anti-inflammatory drugs is preventive against AD, but these medications do not slow down the progression of the disease in already diagnosed patients. There are a number of studies focusing on traditional herbal medicines and small molecules (usually plant secondary metabolites) as potential anti-inflammatory drugs, particulary in respect to cytokine suppression. For instance, ω-3 polyunsaturated fatty acids and a number of polyphenolic phytochemicals have been shown to be effective against inflammation in animal and cell models. Some of these plant secondary metabolites have also been shown to possess antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects. This review will overview the the effects of catechins/proanthocyanidins from green tea, curcumin from turmeric, extracts enriched in bacosides from Brahmi, Ginkgo flavone glycosides, and ω-3 polyunsaturated fatty acids not only counteract one pathophysiological aspect of AD in numerous in vitro and in vivo studies of models of AD, but also ameliorate several of the above mentioned pathologies. The evidence suggests that increased consumption of these compounds might lead to a safe strategy to delay the onset of AD. The continuing investigation of the potential of these substances is necessary as they are promising to yield a possible remedy for this pervasive disease.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 09/2014; 13(7). DOI:10.2174/1871527313666140917110635 · 2.63 Impact Factor
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    • "The main active ingredients of ginkgo biloba extract (GbE) are flavonoids (including meletin, kaempferol and isorhamnetin) and laetones (including ginkgolides and bilobalide). GbE can remove free radicals, protect the endothelial cells of blood vessels, block platelet activating factors, and improve brain circulation.[6],[7] GbE has been widely used in the treatment of dementia, cognitive impairment, peripheral nerve problems, and vascular tinnitus.[8] "
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    ABSTRACT: Given the increasing burden of dementia internationally and the lack of effective treatments, several countries are already recommending the use of ginkgo biloba extract (GbE) in the treatment of dementia, despite the inconsistent research results about its effectiveness.
    Shanghai Archives of Psychiatry 02/2013; 25(1):10-21. DOI:10.3969/j.issn.1002-0829.2013.01.005
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    • "Similarly administration of Gingko biloba and a number of unsaturated fatty acids to rodents have been reported to increase TTR mRNA abundance in cortical neurons as measured by microarray analysis [232-234]. Some of these compounds have had favorable effects in transgenic models of human AD [235,236]. However large studies of at least one of these in human AD patients have failed to show any benefit [237]. Perhaps this is just an example of "too little too late" rather than a conceptual error. "
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    ABSTRACT: Since the mid-1990's a trickle of publications from scattered independent laboratories have presented data suggesting that the systemic amyloid precursor transthyretin (TTR) could interact with the amyloidogenic β-amyloid (Aβ) peptide of Alzheimer's disease (AD). The notion that one amyloid precursor could actually inhibit amyloid fibril formation by another seemed quite far-fetched. Further it seemed clear that within the CNS, TTR was only produced in choroid plexus epithelial cells, not in neurons. The most enthusiastic of the authors proclaimed that TTR sequestered Aβ in vivo resulting in a lowered TTR level in the cerebrospinal fluid (CSF) of AD patients and that the relationship was salutary. More circumspect investigators merely showed in vitro interaction between the two molecules. A single in vivo study in Caenorhabditis elegans suggested that wild type human TTR could suppress the abnormalities seen when Aβ was expressed in the muscle cells of the worm. Subsequent studies in human Aβ transgenic mice, including those from our laboratory, also suggested that the interaction reduced the Aβ deposition phenotype. We have reviewed the literature analyzing the relationship including recent data examining potential mechanisms that could explain the effect. We have proposed a model which is consistent with most of the published data and current notions of AD pathogenesis and can serve as a hypothesis which can be tested.
    Molecular Neurodegeneration 11/2011; 6(1):79. DOI:10.1186/1750-1326-6-79 · 6.56 Impact Factor
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