Effects of ginsenoside Rg1 or 17β-estradiol on a cognitively impaired, ovariectomized rat model of Alzheimer’s disease

Ginsenoside Rg1, which could improve spatial learning and memory, might be a useful agent for preventing and treating cognitive impairment in Alzheimer's disease (AD). The present study was designed to test the neuroprotective effects of ginsenoside Rg1 on an ovariectomized (OVX) and d-galactose (d-gal)-injected rat model of AD, which is characterized with progressive learning and memory deficits, AD-related molecules alteration and differentiation/apoptosis imbalance in hippocampal neurons. OVX Wistar rats received daily injections of d-gal (100mg/kg) combined with different concentrations of ginsenoside Rg1 (5, 10, 20mg/kg) or 17-β-estradiol (E2, 100 μg/kg), or normal saline (NS, 1.0 ml/kg) for 6 weeks. Ovarian steroid deprivation plus d-gal injection led to spatial learning and memory capacity impairments, as well as increased Aβ(1-42) production. Ginsenoside Rg1 and E2-treatment significantly ameliorated these deteriorations in AD rats. Seven weeks after surgery, α-secretase a disintegrin and metallopeptidase domain 10 (ADAM 10) in hippocampus of AD rats was dramatically decreased, while β-secretase β-site APP-cleaving enzyme 1 (BACE 1) increased compared with those in sham-operated ones (P<0.05). Levels of cleaved caspase 3 were increased in the hippocampus of AD rats. Ginsenoside Rg1 and E2-treatment increased ADAM 10 level while reduced BACE 1 level and apoptosis. Moreover, moderate i.e. 10mg/kg/d and high i.e. 20mg/kg/d ginsenoside Rg1 displayed more effective function than low i.e. 5mg/kg/d ginsenoside Rg1. Our findings demonstrate the neuroprotective effects of ginsenoside Rg1 and E2 on AD rats and support the potential application of ginsenoside Rg1 in the treatment of learning and memory impairments in postmenopausal women.