Notoginseng Saponin Rg1 Prevents Cognitive Impairment through Modulating APP Processing in Aβ_1–42-injected Rats

Abstract

With the intensification of the aging process of the world, Alzheimer’s disease (AD), which is the main type of senile dementia, has become a primary problem in the present society. Lots of strategies have been used to prevent and treat AD in animal models and clinical trials, but most of them ended in failure. Panax notoginseng saponins (PNS) contain a variety of monomer compositions which have been separated and identified. Among of the monomer compositions, notoginseng saponin Rg1 (Rg1) accounts for 20% of the cultivation of panax notoginseng roots. And now PNS have been reported to be widely used to treat cardio-cerebrovascular diseases and have neuroprotective effects to restrain the β-amyloid peptide (Aβ)25–35-mediated apoptosis. Moreover, it is reported that PNS could accelerate the growth of nerve cells, increase the length of axons and promote synaptic plasticity. Whether Rg1 can ameliorate the cognitive impairment and the underlying mechanism has not been elucidated. To study the preventive effect of Rg1 on cognitive impairment and the possible mechanism, we established the cognitive impairment model in rats through Aβ_1–42 (2.6 µg/µL, 5 µL) injection and then treated the rats with Rg1 (25, 50 and 100 mg/kg) administered intragastrically for 4 weeks. We observed that Aβ_1–42 could induce spatial learning and memory deficits in rats. Simultaneously, Aβ_1–42 injection also resulted in the reduced neuron number in cornuammonis 1 (CA1) and dentate gyrus (DG) of hippocampus, as well as the increased level of hyperphosphorylated β-amyloid precursor protein (APP) at Thr668 site with up-regulation of β-APP cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) and down-regulation of a disintegrin and metalloprotease domain-containing protein 10 (ADAM10) and insulin-degrading enzyme (IDE). Administration of Rg1 effectively rescued the cognitive impairment and neuronal loss, and inhibited the β-secretase processing of APP through reducing APP-Thr668 phosphorylation and BACE1/PS1 expression, and increasing the expression of ADAM10 and IDE. We concluded that Rg1 might have neuroprotective effects and could promote learning and memory ability, which might be a viable candidate in AD therapy probably through reducing the generation of Aβ and increasing the degradation of Aβ.

Keywords

notoginseng saponin Rg1 / Alzheimer’s disease / spatial learning and memory deficits / β-amyloid peptide / secretase / degrading enzyme

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