Abstract
Ginsenoside F1, the metabolite of Rg1, is one of the most important constituents of Panax ginseng. Although the effects of ginsenosides on amyloid beta (Aβ) aggregation in the brain are known, the role of ginsenoside F1 remains unclear. Here, we investigated the protective effect of ginsenoside F1 against Aβ aggregation in vivo and in vitro. Treatment with 2.5 μM ginsenoside F1 reduced Aβ-induced cytotoxicity by decreasing Aβ aggregation in mouse neuroblastoma neuro-2a (N2a) and human neuroblastoma SH-SY5Y neuronal cell lines. Western blotting, real-time PCR, and siRNA analysis revealed an increased level of insulin-degrading enzyme (IDE) and neprilysin (NEP). Furthermore, liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis confirmed that ginsenoside F1 could pass the blood–brain barrier within 2 h after administration. Immunostaining results indicate that ginsenoside F1 reduces Aβ plaques in the hippocampus of APPswe/PSEN1dE9 (APP/PS1) double-transgenic Alzheimer’s disease (AD) mice. Consistently, increased levels of IDE and NEP protein and mRNA were observed after the 8-week administration of 10 mg/kg/d ginsenoside F1. These data indicate that ginsenoside F1 is a promising therapeutic candidate for AD.
Highlights
Alzheimer’s disease (AD) is a classic cause of dementia
Dulbecco’s modified Eagle’s medium (DMEM), fetal bovine serum (FBS), and phosphate-buffered saline, DMEM/F12, OPTI-MEM, and penicillin-streptomycin solution were purchased from Thermo Fisher Company. trichloroacetic acid (TCA) and acetone were purchased from Fluka (Buchs, Switzerland); Aβ was obtained from Cellmano Biotech (Hefei, China); horseradish peroxidase (HRP)-linked anti-rabbit IgG and HRP-linked antimouse IgG were bought from Cell Signaling Technology (Beverly, MA, USA); insulin-degrading enzyme (IDE) and NEP from Abcam (La Jolla, CA, USA); Aβ and β-actin were purchased from Santa Cruz
We investigated whether ginsenoside F1 affects cell viability in neuronal cells
Summary
Alzheimer’s disease (AD) is a classic cause of dementia. The pathological features of AD include memory loss and cognitive decline [1]. Major lesions are found in the cerebral cortex and hippocampus, which have abnormally hyperphosphorylated neurofibrillary tangles in the neurons and amyloid beta (Aβ) plaque accumulating outside the cell. These pathological characteristics are common, among which the toxic protein Aβ is a major component, and its over-accumulation is reported to be a common phenomenon [2,3]. The main components of Aβ plaques found in AD patients, are natural products of metabolism and contain 36–43 amino acids. Aβ peptides are derived from the β-site proteolytic cleavage of amyloid precursor protein (APP) by a β-secretase, and γ-secretase, a protein complex with presenilin 1 at its catalytic core [4]. Aβ levels in the brain can be mediated by the dynamic equilibrium between Aβ production from APP and removal by amyloid-degrading enzymes (ADEs) [5]
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