Panaxcerol D from Panax ginseng ameliorates the memory impairment induced by cholinergic blockade or Aβ25-35 peptide in mice

Abstract

Background: Alzheimer's disease (AD) has memory impairment associated with aggregation of amyloid plaques and neurofibrillary tangles in the brain. Although anti-amyloid β (Aβ) protein antibody and chemical drugs can be prescribed in the clinic, they show adverse effects or low effectiveness. Therefore, the development of a new drug is necessarily needed. We focused on the cognitive function of Panax ginseng and tried to find active ingredient(s). We isolated panaxcerol D, a kind of glycosyl glyceride, from the non-saponin fraction of P. ginseng extract.

Methods: We explored effects of acute or sub-chronic administration of panaxcerol D on cognitive function in scopolamine- or Aβ_25-35 peptide-treated mice measured by several behavioral tests. After behavioral tests, we tried to unveil the underlying mechanism of panaxcerol D on its cognitive function by Western blotting.

Results: We found that pananxcerol D reversed short-term, long-term and object recognition memory impairments. The decreased extracellular signal-regulated kinases (ERK) or Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) in scopolamine-treated mice was normalized by acute administration of panaxcerol D. Glial fibrillary acidic protein (GFAP), caspase 3, NF-kB p65, synaptophysin and brain-derived neurotrophic factor (BDNF) expression levels in Aβ_25-35 peptide-treated mice were modulated by sub-chronic administration of panaxcerol D.

Conclusion: Pananxcerol D could improve memory impairments caused by cholinergic blockade or Aβ accumulation through increased phosphorylation level of ERK or its anti-inflammatory effect. Thus, panaxcerol D as one of non-saponin compounds could be used as an active ingredient of P. ginseng for improving cognitive function.

Keywords: ERK and CaMKⅡ pathway; Learning and memory; Panax ginseng; Panaxcerol D; p65-BDNF pathway.

Graphical abstract

Fig. 1

The chemical structure of panaxcerol D.

Fig. 2

Effects of panaxcerol D on cognitive function measured by Y-maze test, NORT, and PAT in mice The spontaneous alternation (A) in Y-maze test, the object preference ratio (B) in NORT, and the step-through latencies in the acquisition trial and retention trial (C) in PAT were presented. Data were presented means ± S.E.M. (n = 8-10/group) (∗∗∗P < 0.001 versus the vehicle-administered group; ^#P < 0.05 versus the scopolamine administered group; ^###P < 0.001 versus the scopolamine administered group). Con, control.

Fig. 3

Effects of sub-chronic panaxcerol D treatment on Aβ_25-35 peptide-induced memory impairment in Y-maze test, NORT, and PAT in mice The spontaneous alternation (A) in Y-maze test, the object preference ratio (B) in NORT, and the step-through latencies in the acquisition trial and retention trial (C) in PAT were presented. Data were presented means ± S.E.M. (n = 9-10/group) (∗∗∗P < 0.001 versus the vehicle-administered group; ^##P < 0.01 versus the scopolamine administered group; ^###P < 0.001 versus the scopolamine administered group). Con, control.

Fig. 4

Effects of panaxcerol D on the scopolamine-induced phosphorylation levels of ERK and CaMKⅡ in the hippocampus The immunoreactivity (A) and quantitative analysis of expression levels of ERK (B) and CaMKⅡ (C) were presented. Data were presented means ± S.E.M. (n = 5-6/group) (∗∗∗P < 0.001 versus the vehicle-administered group; ^##P < 0.01 versus the scopolamine administered group; ^###P < 0.001 versus the scopolamine administered group). Con, control.

Fig. 5

Effects of sub-chronic treatment of panaxcerol D on Aβ_25-35 peptide-induced the expression level of GFAP and caspase 3 and phosphorylation level of ERK and p65 and expression level of synaptophysin and BDNF in the cortex The immunoreactivity (A) and the quantitative analysis (B) of expression levels of GFAP, caspase 3, synaptophysin and BDNF or phosphorylation levels of ERK and p65 were presented. Data were shown as the means ± S.E.M. (n = 5-6/group) (∗P < 0.05 versus the vehicle-administered group; ∗∗P < 0.01 versus the vehicle-administered group; ^#P < 0.05 versus the Aβ_25-35 administered group; ^##P < 0.01 versus the Aβ_25-35 administered group). PD, panaxcerol D; SYP, synaptophysin; Con, control.