Abstract
This present study was designed to investigate the different effects of ginsenosides Rb1 and Rg1 on improving cognitive deficits in 4-month-old SAMP8 mice. Mice were divided into six groups, including the SAMP8 group, the SAMP8 + Donepezil (1.6 mg/kg) group, the SAMP8 + Rb1 (30 and 60 µmol/kg), and SAMP8 + Rg1 (30 and 60 µmol/kg) groups. SAMR1 mice of the same age were used as the control group. Ginsenosides and donepezil were administrated orally to animals for 8 weeks, then the learning and memory ability of mice were measured by using Morris water maze (MWM) test, object recognition test and passive avoidance experiments. The possible mechanisms were studied including the anti-glial inflammation of Rb1 and Rg1 using HE staining, immunohistochemistry and western blot experiments. Results revealed that Rb1 and Rg1 treatment significantly improved the discrimination index of SAMP8 mice in the object recognition test. Rb1 (60 µmol/kg) and Rg1 (30, 60 µmol/kg) could significantly shorten the escape latency in the acquisition test of the MWM test in SAMP8 mice. Furthermore, Rb1 and Rg1 treatments effectively reduced the number of errors in the passive avoidance task in SAMP8 mice. Western blot experiments revealed that Rb1 showed higher effect than Rg1 in decreasing protein expression levels of ASC, caspase-1 and Aβ in the hippocampus of SAMP8 mice, while Rg1 was more effective than Rb1 in decreasing the protein levels of iNOS. In addition, although Rb1 and Rg1 treatments showed significant protective effects in repairing neuronal cells loss and inhibiting the activation of astrocyte and microglia in hippocampus of SAMP8 mice, Rb1 was more effective than Rg1. These results suggest that Rb1 and Rg1 could improve the cognitive impairment in SAMP8 mice, and they have different mechanisms for the treatment of Alzheimer's disease.
Highlights
Alzheimer's disease (AD) is a neurodegenerative disease with complex pathogenic factors
Our study showed that ginsenosides Rb1 and Rg1 could ameliorate memory impairments in SAMP8 mice and suggested that their action may be mediated via modulation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, decreasing tumor necrosis factor-a (TNF-a) level, astrocytes, and microglias activation, ameliorating oxidative stress, and inhibiting expression of p-Nuclear factor-kB (NF-kB)-p65, ASC, caspase-1, and inducible nitric oxide synthase (iNOS) in hippocampus
SAMP8 mice show severe inflammatory reactions and oxidative stress related to aging, which can exacerbate neurological damage and cognitive decline (Jiang et al, 2018; Puigoriol-Illamola et al, 2018)
Summary
Alzheimer's disease (AD) is a neurodegenerative disease with complex pathogenic factors. Its main symptoms are cognitive impairment, execution disorder, memory impairment, obvious mental disorder, sleep disorder, and even behavioral abnormalities (Yang et al, 2017; Yutaro et al, 2018). Many studies have indicated the cardinal features of Alzheimer pathology are amyloid plaques, neurofibrillary tangles (NFTs), associated with astrogliosis and microglial activation (Lane et al, 2018; Boumenir et al, 2019). Apoptotic process closely associated with inflammasome, and lead to neuronal cell death in AD (Xingxing and Tao, 2018). Microglia and astrocyte are the main cells involved in neuroinflammatory reactions. Activated microglia and astrocyte can produce pro-inflammatory cytokines such as tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), and interleukin-6 (IL-6) (Kima et al, 2019)
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