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Long-term treatment with Ginkgo biloba extract EGb 761 improves symptoms and pathology in a transgenic mouse model of Alzheimer’s disease
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease characterized by extracellular deposits of amyloid β peptide (Aβ) and microglia-dominated neuroinflammation. The therapeutic options for AD are currently limited. In this study, we investigated the antiinflammatory effects and the underlying molecular mechanisms of Ginkgo biloba extract EGb 761 when administered to TgCRND8 AD mice, which overexpress human Alzheimer's amyloid precursor protein (APP) specifically in neurons. We gave APP-transgenic mice EGb 761 as a dietary supplement for 2 or 5months. Plasma concentrations of EGb 761 components in mice were in the same range as such concentrations in humans taking EGb 761 at the recommended dose (240mg daily). Treatment with EGb 761 for 5months significantly improved the cognitive function of the mice as measured by the Barnes Maze test. It also attenuated the loss of synaptic structure proteins, such as PSD-95, Munc18-1, and SNAP25. Treatment with EGb 761 for 5months inhibited microglial inflammatory activation in the brain. The effects of treatment with EGb 761 for 2months were weak and not statistically significant. Moreover, EGb 761 activated autophagy in microglia. Treatment with EGb 761 decreased Aβ-induced microglial secretion of TNF-α and IL-1β and activation of caspase-1, both of which were abolished by the inhibition of autophagy. Treatment with EGb 761 also reduced the concentrations of NLRP3 protein that colocalized with LC3-positive autophagosomes or autolysosomes in microglia. Additionally, long-term treatment with EGb 761 may reduce cerebral Aβ pathology by inhibiting β-secretase activity and Aβ aggregation. Therefore, long-term treatment with G. biloba extract EGb 761, a clinically available and well-tolerated herbal medication, ameliorates AD pathology by antiinflammatory and Aβ-directed mechanisms.
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“Moreover, EGb 761 minimized synaptic loss and cognitive impairment in AD, possibly by preventing Aβ aggregation and fostering neuroprotection and neurogenesis [99].”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [99]
In the citing paper
“Xu Liu et al. revealed that long-term oral administration of GB extract EGb 761 alleviated AD pathogenesis by promoting autophagy and reducing neuroinflammation.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [99]
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Metadata
- Authors
- Liu, X., Hao, W., Qin, Y., Decker, Y., Wang, X., Burkart, M., Schötz, K., Menger, M. D., Fassbender, K., & Liu, Y.
- Affiliations
- Saarland University (DE)
- Soochow University (CN)
- Dr Willmar Schwabe (Germany) (DE)
- Corresponding author
- Liu, Xu
- Liu, Yang
- ORCID
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 46
- Pages
- 121-131
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2032028277
- Cited by
- 149
- References
- 61
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 18 · 2023: 12 · 2022: 15 · 2021: 13 · 2020: 13 · 2019: 12 · 2018: 18 · 2017: 10 · 2016: 13 · 2015: 2
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Willmar Schwabe GmbH & Co. KG
- EU (211696)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Ginkgo biloba and Cashew Applications
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, Ginkgo biloba extract EGb 761, TgCRND8 mice, amyloid-beta, microglial neuroinflammation, autophagy, NLRP3 inflammasome, synaptic proteins, cognitive function, beta-secretase, amyloid fibril formation, herbal medicine, anti-inflammatory therapy
- MeSH terms
- Disks Large Homolog 4 Protein, Ginkgo Extract, Alzheimer Disease, Animals, Brain, Membrane Proteins, Mice, Transgenic, Neurons, Plant Extracts, Amyloid beta-Peptides, Neuroprotective Agents, Maze Learning, Ginkgo biloba, Synaptosomal-Associated Protein 25, Mice, Guanylate Kinases, Munc18 Proteins
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