diospyros and Memory-Disorders

Amyloid-β peptide (Aβ) initiates a cascade of pathological events, including activation of microglial cells, oxidative stress, and inflammation, leading to neuronal death and the typical pathological changes in Alzheimer's disease (AD). Flavonoids have been reported to exert neuroprotective activities, not only through their generally accepted antioxidant effects, but also through their ability to protect against neurotoxin-induced injury. Flavonoids reduce Aβ production, inhibit neuroinflammation, increase cerebrovascular function, and improve cognitive performance. Here, we analyzed the effects of a flavonoid-rich ethanol extract from the leaves of Diospyros kaki (FLDK) in APP/PS1 transgenic mice. We found that oral treatment with FLDK reversed learning and memory impairment, reduced Aβ burden and expression of β-site amyloid precursor protein cleavage enzyme 1 (BACE1), and decreased microglial activation in senile plaques. FLDK restored antioxidant enzyme activities, as well as reduced the lipid peroxidation product, malondialdehyde, and inflammatory mediators. These results demonstrate that FLDK alleviates cognitive decline and reduces Aβ burden, microglial activation, oxidative stress, and inflammation responses. Thus, FLDK treatment may be a potential therapeutic strategy for preventing and treating AD, at least in part via its anti-oxidant and anti-inflammatory biological activities and its effect on the Aβ producing enzyme BACE1.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Cognition; Cognition Disorders; Cognitive Dysfunction; Diospyros; Ethanol; Flavonoids; Humans; Memory Disorders; Mice; Mice, Transgenic; Microglia; Neuroimmunomodulation; Oxidative Stress; Plant Leaves; Plaque, Amyloid; Presenilin-1

Mice were subcutaneously injected with d-galactose (D-gal, 150 mg/kg per day) for 6 weeks and were administered high molecular weight persimmon condensed tannin (HMWPT) simultaneously. After 6 weeks of treatment, the animal behavior was observed in the open field test and water maze test, and the morphology of hippocampus and skin were checked. Meanwhile, the activities of antioxidant enzymes, the levels of non-enzymatic antioxidants, as well as malondialdehyde (MDA) were evaluated. The results indicated that HMWPT markedly inhibited the d-gal induced learning and memory impairment in both open field test and Morris water maze. Biochemical examination revealed that HMWPT significantly increased the decreased activities of superoxide dismutase (SOD), catalase (CAT), elevated the lowered total anti-oxidation capability (T-AOC), glutathione (GSH) and hydroxyproline (Hyp) contents (p<0.01 or p<0.05), and decreased the raised monoamine oxidase (MAO), total cholinesterase (TChE) activities and MDA level (p<0.01) in serum, liver or brain of aging mice induced by d-gal in a dose-dependent fashion. Furthermore, HMWPT significantly and (p<0.01) attenuated the d-gal induced number decrease, neuronal degeneration and karyopycnosis in cells in the hippocampus and decrease of thickness of skin epidermis and dermis.

Topics: Aging; Animals; Antioxidants; Behavior, Animal; Catalase; Cholinesterases; Cognition Disorders; Diospyros; Galactose; Glutathione; Hippocampus; Hydroxyproline; Lipid Peroxidation; Male; Malondialdehyde; Maze Learning; Memory Disorders; Mice; Molecular Weight; Monoamine Oxidase; Oxidative Stress; Skin; Superoxide Dismutase; Tannins

Senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence, shows age-related deficits in learning and memory. We investigated the effect of oligomeric proanthocyanidins (oligomers) on memory impairment using the SAMP8 model involving the oral administration of oligomers for 5 weeks. To analyse memory improvement in SAMP8, we performed Morris water maze, object location and object recognition tests. The oral administration of oligomers improved spatial and object recognition impairment in SAMP8. Expressions of phosphorylated neurofilament-H (P-NF-H, axon marker), microtubule-associated proteins (MAP) 2a and 2b (MAP2; dendrite marker) and synaptophysin were increased in the brains of SAMP8-administered oligomers. In particular, the expression of P-NF-H was significantly elevated in the hippocampal CA1. This indicates that oligomers result in an increase in the densities of axons, dendrites and synapses. To investigate the protective mechanisms of oligomers against brain dysfunction with ageing, we carried out a receptor tyrosine kinase phosphorylation antibody array, and clarified that the administration of oligomers led to an increase in the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2, suggesting the neuroprotective role of oligomers. The phosphorylation of VEGFR-2 was more greatly increased in the hypothalamus and choroid plexus than in other brain regions of SAMP8. Memory in oligomer-treated mice was impaired by SU1498, a VEGFR-2-specific antagonist. Elucidating the relationship between memory impairment with ageing and VEGFR-2 signalling may provide new suggestions for protection against memory deficit in the ageing brain.

Topics: Aging; Animals; Brain; Cinnamates; Diospyros; Disease Models, Animal; Fruit; Male; Maze Learning; Memory Disorders; Mice; Mice, Inbred Strains; Microtubule-Associated Proteins; Neurofilament Proteins; Neurons; Neuroprotective Agents; Phosphorylation; Phytotherapy; Plant Extracts; Proanthocyanidins; Spatial Behavior; Synaptophysin; Vascular Endothelial Growth Factor Receptor-2