title: 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.
authors: Department of Neurology, University of the Saarland, 66421 Homburg/Saar, Germany; German Institute for Dementia Prevention (DIDP), University of the Saarland, 66421 Homburg/Saar, Germany.
authors: Xu
authors: X
authors: Liu
authors: Department of Neurology, University of the Saarland, 66421 Homburg/Saar, Germany; German Institute for Dementia Prevention (DIDP), University of the Saarland, 66421 Homburg/Saar, Germany.
authors: Wenlin
authors: W
authors: Hao
authors: Department of Neurology, University of the Saarland, 66421 Homburg/Saar, Germany; German Institute for Dementia Prevention (DIDP), University of the Saarland, 66421 Homburg/Saar, Germany; The Institute of Neuroscience, Soochow University, 215123 Suzhou, China.
authors: Yiren
authors: Y
authors: Qin
authors: Department of Neurology, University of the Saarland, 66421 Homburg/Saar, Germany; German Institute for Dementia Prevention (DIDP), University of the Saarland, 66421 Homburg/Saar, Germany.
authors: Yann
authors: Y
authors: Decker
authors: Department of Pharmacy, Putuo People's Hospital, 200060 Shanghai, China.
authors: Xuan
authors: X
authors: Wang
authors: Dr. Willmar Schwabe GmbH & Co. KG, 76227 Karlsruhe, Germany.
authors: Martin
authors: M
authors: Burkart
authors: Preclinical Research, Dr. Willmar Schwabe GmbH & Co. KG, 76227 Karlsruhe, Germany.
authors: Karl
authors: K
authors: Schötz
authors: Institute for Clinical and Experimental Surgery, University of the Saarland, 66421 Homburg/Saar, Germany.
authors: Michael D
authors: MD
authors: Menger
authors: Department of Neurology, University of the Saarland, 66421 Homburg/Saar, Germany; German Institute for Dementia Prevention (DIDP), University of the Saarland, 66421 Homburg/Saar, Germany.
authors: Klaus
authors: K
authors: Fassbender
authors: Department of Neurology, University of the Saarland, 66421 Homburg/Saar, Germany; German Institute for Dementia Prevention (DIDP), University of the Saarland, 66421 Homburg/Saar, Germany. Electronic address: a.liu@mx.uni-saarland.de.
authors: Yang
authors: Y
authors: Liu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000076122:Disks Large Homolog 4 Protein; D020441:Ginkgo biloba; D051528:Guanylate Kinases / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051938:Munc18 Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D000096983:Ginkgo Extract
chemical_list: D016229:Amyloid beta-Peptides; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D008565:Membrane Proteins; D051938:Munc18 Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; D050825:Synaptosomal-Associated Protein 25; C501447:Dlg4 protein, mouse; C497938:Stxbp1 protein, mouse; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract
keywords: Alzheimer’s disease; Autophagy; Aβ; Inflammation; Microglia; Neurodegeneration