Pseudoginsenoside-F11 alleviates cognitive deficits and Alzheimer's disease-type pathologies in SAMP8 mice.

Alzheimer's disease (AD) is a common neurodegenerative disease which is characterized by aggregation of amyloid beta (Aβ) and hyperphosphorylated tau. We previously reported that pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, improved cognitive function and reduced Aβ aggregation in APP/PS1 mice, a familial AD model. Here, we chose senescence-accelerated mouse prone 8 (SAMP8) mice, a widely used model of aging, to investigate the effect of PF11 on sporadic AD. PF11 was orally administered to male 6-month-old SAMP8 mice for 3 months. Consistent with previous studies, SAMP8 mice showed several AD-type pathologies including cognitive impairment, Aβ deposition and tau hyperphosphorylation. We found increased protein levels of cytoplasmic amyloid precursor protein (APP) and β-site APP cleavage enzyme 1 (BACE1) in the hippocampus and cortex of SAMP8 mice. The protein level of demethylated protein phosphatase 2A (PP2A) was elevated in SAMP8 animals and the protein level of leucine carboxyl methyltransferase 1 (LCMT-1) was reduced. PF11 attenuated learning and memory impairments in the novel object recognition test and Morris water maze. PF11 promoted the transport of APP from cytoplasm to plasma membrane and decreased the abnormally high expression of BACE1 in hippocampus and cortex of SAMP8 mice. The elevated protein level of demethylated PP2A and the reduced expression of LCMT-1 in hippocampus and cortex of SAMP8 were also attenuated by PF11. Together, our findings indicate that PF11 has beneficial effects on AD-like pathological changes in SAMP8 mice and may act by inhibiting amyloidogenic processing of APP and attenuating tau hyperphosphorylation.