Astragalus polysaccharide alleviates cognitive impairment and β-amyloid accumulation in APP/PS1 mice via Nrf2 pathway

• Published in: Biochemical and biophysical research communications 2020-10, Vol.531 (3), p.431-437
• Main Authors: Qin, Xiude, Hua, Jun, Lin, Song-jun, Zheng, Hao-tao, Wang, Jian-jun, Li, Wei, Ke, Jin-ju, Cai, Hao-bin
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Alzheimer’s disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Animals; Apoptosis - drug effects; Astragalus Plant - chemistry; Astragalus polysaccharide; Cognition - drug effects; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - physiopathology; Male; Mice, Inbred C57BL; Mice, Transgenic; Neurons - drug effects; Neurons - pathology; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidative Stress - drug effects; Polysaccharides - pharmacology; Polysaccharides - therapeutic use; Presenilin-1 - metabolism; Signal Transduction; β-amyloid
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.07.122

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and its etiology and pathogenesis are not fully understood. Astragalus polysaccharide (APS) has many pharmacological activities, but there are few reports about its role in AD. Using the common AD model APP/PS1 mice, it was found that the expression of Keap1 (a negative regulatory factor of Nrf2), the protein level of cytoplasmic Nrf2 and the content of MDA were increased significantly, while the mRNA level of Nrf2, the expression of Nrf2 in nucleus and the contents of SOD and GSH-Px were decreased significantly. APS treatment significantly increased the expression of Nrf2 in the nucleus but decreased its expression in the cytoplasm, and restored the expression levels of Keap1, SOD, GSH-Px and MDA. When APP/PS1 mice were treated with APS and injected with Nrf2 siRNA, the down-regulation of Nrf2 expression significantly blocked the regulation of APS on oxidative stress. Continuing to test the physiological function of AD mice showed that the spatial learning and memory abilities of APP/PS1 mice were impaired, the apoptosis of brain cells and the content of β-amyloid (Aβ) were significantly increased. APS treatment significantly improved the cognitive ability of APP/PS1 mice, reduced apoptosis and the accumulation of Aβ, but the above effects of APS were blocked by Nrf2 siRNA injection. Therefore, APS can activate Nrf2 pathway to improve the physiological function of AD mice, which may have important clinical application value. •APS activates Nrf2 pathway in AD mice.•APS activates Nrf2 pathway to regulate oxidative stress in AD mice.•APS activates Nrf2 pathway to improve apoptotic level and cognitive ability of AD mice.•APS activates Nrf2 pathway to reduce the accumulation of Aβ in AD mice.