diospyros and Cognitive-Dysfunction

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

Topics: Acetates; Animals; Antioxidants; Apoptosis; Brain; Cell Count; Cognition; Cognitive Dysfunction; Diospyros; JNK Mitogen-Activated Protein Kinases; Male; Maze Learning; Membrane Potential, Mitochondrial; Mice; Mitochondria; Neurons; Neuroprotective Agents; Plant Extracts; Proto-Oncogene Proteins c-akt; Pyramidal Cells; Signal Transduction