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

Augustin, Sabine; Rimbach, Gerald; Augustin, Kay; Schliebs, Reinhard; Wolffram, Siegfried; Cermak, Rainer

doi:10.1016/j.abb.2008.10.032

Cited by 58 publications

(37 citation statements)

References 41 publications

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“…Antioxidant agents are reported to have a mediating role in the prevention of cell damage in the ageing brain (Oyama et al 1994). There are animal studies to support its protective role on cardiomyocytes (Schneider et al 2008), intestinal inflammation (Kotakadi et al 2008), liver carcinogenesis (Dias et al 2008), intermittent claudication (Pittler & Ernst, 2000), hippocampal loss (Takuma et al 2007) and other neuronal damage (Augustin et al 2009;Rojas et al 2008;Saleem et al 2008). Ginkgo has antioxidant properties (Maclennan et al 2002) and has been found to improve brain circulation at the microvascular level (Kubota et al 2001;Sun et al 2003;Yan et al 2008).…”

Section: Background and Hypothesismentioning

confidence: 94%

Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic schizophrenia

Singh

Chan

2009

Int. J. Neuropsychopharm.

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This study aimed to review the roles of antioxidants in the pathophysiology of schizophrenia, whether the properties of ginkgo can ameliorate symptoms of this illness, and evaluate available literature to test this assumption. This review is based upon published works on antioxidants and ginkgo. A primary electronic search for meta-analysis on the usage of ginkgo or its derived products in schizophrenia was conducted using Pubmed, Cochrane Library, EMBASE, CINAHL, PsycINFO and AMED. Inclusion criteria were: criteria-based diagnosis of schizophrenia, randomized case assignment, use of ginkgo as an add-on therapy, and assessment using standardized rating scales to measure the state of psychopathology for negative and total symptoms of schizophrenia. Additionally, a detailed review was undertaken to investigate if antioxidants are involved in development of psychotic symptoms in schizophrenia. The six studies that fulfilled the selection criteria were constituted of 466 cases on ginkgo and 362 cases on placebo. They all used the Scale for the Assessment of Negative Symptoms (SANS) to measure negative symptoms, and the Scale for the Assessment of Positive Symptoms (SAPS) or the Brief Psychiatric Rating Scale (BPRS) to measure total symptoms. Difference between ginkgo and control groups from their pre- and post-trial scores and its pooled standard deviation were used to compute standardized mean difference (SMD). Ginkgo as an add-on therapy to antipsychotic medication produced statistically significant moderate improvement (SMD=-0.50) in total and negative symptoms of chronic schizophrenia. Ginkgo as add-on therapy ameliorates the symptoms of chronic schizophrenia. The role of antioxidants in pathogenesis of schizophrenia has also been explored.

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Section: Background and Hypothesismentioning

confidence: 94%

Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic schizophrenia

Singh

Chan

2009

Int. J. Neuropsychopharm.

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“…64 At the APP processing level, it was demonstrated that longterm treatment (16 months) with Ginkgo biloba extract (EGb761) significantly lowered APP protein levels in a transgenic mouse model of AD, suggesting that its potential neuroprotective properties may be, at least partly, related to its APP lowering effects. 65 Also, brain parenchymal and cerebral vascular β-amyloid deposits were diminished in tannic acid treated PSAPP mice, suggesting that it acts as a natural β-secretase inhibitor. 66 Natural flavonoids were shown to potently inhibit BACE-1 activity and reduce the level of secreted Aβ in primary cortical neurons, 67 whereas epigallocatechin-3-gallate and curcumin suppress amyloid beta-induced BACE-1 upregulation in neuronal cultures.…”

Section: ■ Flavonoidsmentioning

confidence: 97%

Flavonoids as Therapeutic Compounds Targeting Key Proteins Involved in Alzheimer’s Disease

Baptista

Henriques

Silva

et al. 2014

ACS Chem. Neurosci.

161

111

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Alzheimer's disease is characterized by pathological aggregation of protein tau and amyloid-β peptides, both of which are considered to be toxic to neurons. Naturally occurring dietary flavonoids have received considerable attention as alternative candidates for Alzheimer's therapy taking into account their antiamyloidogenic, antioxidative, and anti-inflammatory properties. Experimental evidence supports the hypothesis that certain flavonoids may protect against Alzheimer's disease in part by interfering with the generation and assembly of amyloid-β peptides into neurotoxic oligomeric aggregates and also by reducing tau aggregation. Several mechanisms have been proposed for the ability of flavonoids to prevent the onset or to slow the progression of the disease. Some mechanisms include their interaction with important signaling pathways in the brain like the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways that regulate prosurvival transcription factors and gene expression. Other processes include the disruption of amyloid-β aggregation and alterations in amyloid precursor protein processing through the inhibition of β-secretase and/or activation of α-secretase, and inhibiting cyclin-dependent kinase-5 and glycogen synthase kinase-3β activation, preventing abnormal tau phosphorylation. The interaction of flavonoids with different signaling pathways put forward their therapeutic potential to prevent the onset and progression of Alzheimer's disease and to promote cognitive performance. Nevertheless, further studies are needed to give additional insight into the specific mechanisms by which flavonoids exert their potential neuroprotective actions in the brain of Alzheimer's disease patients. KEYWORDS: Flavonoids, Alzheimer's disease, amyloid precursor protein, amyloid beta, BACE-1, tau, signaling A lzheimer's disease (AD) is a neurodegenerative disorder and the most common form of dementia worldwide. The major histopathological hallmarks of AD include proteinous aggregates in the form of neurofibrillary tangles (NFTs), consisting of hyperphosphorylated tau 1,2 and extracellular senile plaques, which are deposits of heterogeneously sized small peptides of amyloid-β (Aβ) that are formed via sequential proteolytic cleavages of the amyloid precursor protein (APP) 3 (Figure 1). Dominant mutations in APP, presenilin-1 (PS1) or PS2 are responsible for the early onset or familial form of AD. These mutations have been shown to profoundly alter APP metabolism, favoring the production of aggregation-prone Aβ species, these findings formed the basis for the "amyloid cascade hypothesis" of AD pathogenesis. This broadly accepted hypothesis states that the generation of neurotoxic Aβ peptides by β-secretase and γ-secretase are at the basis of AD pathophysiology. Other hallmarks of this disease, like neurotransmitter changes 4,5 and neuronal and synapse loss in the neocortex and the hippocampus 6,7 develop as a consequence of this event.■ AMYLOID PRECURSOR PROTEIN APP belongs to a protein f...

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“…It is suggested that compounds of natural origin, such as extracts from Ginkgo biloba and active component of the medicinal herb Salvia miltiorrhiza could be proposed for the treatment and prevention of AD [123][124][125][126]. Polyphenolic compounds, components of red wine, could be used for the prevention and/or therapy of AD [127].…”

Section: Alzheimer's Disease Some Therapeutic Strategiesmentioning

confidence: 99%

Colostral Proline-Rich Polypeptides – Immunoregulatory Properties and Prospects of Therapeutic Use in Alzheimers Disease

Janusz¹,

Zabłocka

2010

CAR

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A proline-rich polypeptide complex (PRP), subsequently called Colostrinin(CLN), was first isolated from ovine colostrum, was shown to possess immunoregulatory properties, including effects on the maturation and differentiation of murine thymocytes and humoral and cellular immune responses, both in vivo and in vitro. PRP seems to restore balance in cellular immune functions and is not species specific. PRP is a complex of peptides of molecular masses ranging from 500 to 3000 Da. The polypeptide contains 25% proline and 40% hydrophobic amino acids. PRP shows a regulatory activity in cytokine (IFN, TNF-alpha, IL-6, IL-10) induction and possesses the ability to inhibit the overproduction of oxygen reactive species and nitric oxide. Besides its immunoregulatory activity, PRP also showed psychotropic properties, improving cognitive activity and behavior of old rats, humans, and chickens. The properties of PRP prompted the authors to propose the complex for the treatment neurodegenerative disorders. Beneficial effects of PRP/Colostrinin were shown for the first time in double-blind placebo-controlled trials and long-term open-label studies. The results were confirmed in multicenter clinical trials. A very important property of PRP/Colostrinin is the prevention of Abeta aggregation and the disruption of already existing aggregates. The same properties were expressed by one of PRP's components, a nonapeptide (NP). Moreover, PRP modulates neurite outgrowth, suppresses uncontrolled activation of cells, reduces 4-HNE-mediated cellular damage, and modulates expression in cellular redox regulation, cell proliferation, and differentiation. Its biological response modifying activity can play an important role in its use in the treatment of Alzheimer's disease.

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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

Cited by 58 publications

References 41 publications

Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic schizophrenia

Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic schizophrenia

Flavonoids as Therapeutic Compounds Targeting Key Proteins Involved in Alzheimer’s Disease

Colostral Proline-Rich Polypeptides – Immunoregulatory Properties and Prospects of Therapeutic Use in Alzheimers Disease

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