ligustilide and Memory-Disorders

Alzheimer's disease (AD) is an age-related neurodegenerative disease. The main active component in

Topics: 4-Butyrolactone; Aging; Animals; Apoptosis; Brain; Inflammation; Male; Maze Learning; Memory Disorders; Mice; Mitochondria; Neuroprotective Agents; Oxidative Stress; Spatial Memory

Klotho, an aging-suppressor gene, encodes a protein that potentially acts as a neuroprotective factor by modulating insulin-like growth factor 1 signaling and oxidative stress. In the present study, we investigated the potential role of Klotho in the therapeutic effect of ligustilide against Alzheimer's disease (AD)-like neuropathologies and memory impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. Ligustilide treatment (10 and 40 mg/kg for 8 weeks, intragastrically) in 10-month-old SAMP8 mice reduced memory deficits, amyloid-β(1)-42 accumulation, tau phosphorylation, and neuron loss, increased mitochondrial manganese-superoxide dismutase and catalase expression and activity, and decreased malondialdehyde, protein carbonyl, and 8-hydroxydesoxyguanosine levels in the brain. Ligustilide upregulated Klotho expression in the cerebral choroid plexus and serum, decreased Akt and Forkhead box class O1 phosphorylation. Moreover, ligustilide inhibited the insulin-like growth factor 1 pathway and induced Forkhead box class O1 activation in 293T cells along with Klotho upregulation. An inverse correlation was found between Klotho expression and the AD phenotype, suggesting that Klotho might be a novel therapeutic target for age-related AD, and Klotho upregulation might contribute to the neuroprotective effect of ligustilide against AD.

Topics: 4-Butyrolactone; Aging; Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Cells, Cultured; Disease Models, Animal; Forkhead Box Protein O1; Forkhead Transcription Factors; Gene Expression Regulation, Developmental; Glucuronidase; Insulin-Like Growth Factor I; Klotho Proteins; Male; Memory Disorders; Mice; Mice, Inbred Strains; Molecular Targeted Therapy; Neuroprotective Agents; Oxidative Stress; Peptide Fragments; Phosphorylation; Signal Transduction; tau Proteins; Up-Regulation

We investigated the effect of Z-ligustilide (LIG) on scopolamine-induced memory impairment in ICR mice. LIG (2.5-40 mg/kg) or tacrine (10 mg/kg) was orally administrated for 26 days. Behavior was examined in the Morris water maze and Y-maze after scopolamine administration (2 mg/kg, i.p.). The central acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities were assessed spectrophotometrically. LIG significantly improved spatial long-term memory and short-term memory impairment, inhibited AChE activity and increased ChAT activity. Moreover, LIG and tacrine showed the comparable efficacy in both neurobehavioral and cholinergic evaluation. These data suggest that LIG may alleviate memory deficits probably via enhancing cholinergic function.

Topics: 4-Butyrolactone; Acetylcholinesterase; Angelica; Animals; Choline O-Acetyltransferase; Cholinergic Agents; Male; Maze Learning; Memory; Memory Disorders; Mice; Mice, Inbred ICR; Phytotherapy; Plant Extracts; Plant Roots; Scopolamine; Tacrine