Notoginsenoside R1 (NTR1) is the main active ingredient of the well-known traditional
Chinese herbal medicine Panax notoginseng, the root of Panax notoginseng (Burk.) F. H. Chen.
Studies demonstrated that NTR1 may have some neuronal protective effects. Alzheimer’s disease (AD) is a
neurodegenerative disease characterized by β -amyloid protein (Aβ) deposition, neurofibrillary tangle formation and
neuronal loss. This study was designed to explore the protective effect of NTR1 on an APP/PS1 double-transgenic mouse
model of AD and investigate the possible mechanism. The 3-month-old mice were fed with 5 mg/(kg•d), 25 mg/(kg•d)
NTR1 or vehicle via oral gavage for 3 months and changes in behavior, neuropathology, and amyloid pathology were
investigated. The mice with NTR1 treatment showed significant amelioration in the cognitive function and increased
choline acetyl transferase expression, as compared to the vehicle treated mice. NTR1 treatment inhibited Aβ accumulation
and increased insulin degrading enzyme expression in both APP/PS1 mice and N2a-APP695sw cells, suggesting that of
NTR1 may exert its protective effects through the enhancement of the Aβ degradation. Furthermore, our data showed that
the increased level of peroxisome proliferator-activated receptor γ (PPARγ) and the up-regulation of insulin degrading
enzyme induced by NTR1 were inhibited by administration of GW9662 (a PPARγ antagonist), indicating that the effect of
NTR1 was mediated, at least in part, by PPARγ. Thus, our findings provide the evidences that NTR1 has protective effect
on AD mouse model and NTR1 may be a potential candidate for AD treatment.