Effect of Astragaloside IV on Neural Stem Cell Transplantation in Alzheimer’s Disease Rat Models

Abstract

Stem cell-based therapy is a promising treatment strategy for neurodegenerative diseases such as Alzheimer's disease (AD). However, the mechanism underlying the maintenance of renewal and replacement capabilities of endogenous progenitor cells or engrafted stem cells in a pathological environment remains elusive. To investigate the effect of astragaloside IV (ASI) on the proliferation and differentiation of the engrafted neural stem cells (NSCs), we cultured NSCs from the hippocampus of E14 rat embryos, treated the cells with ASI, and then transplanted the cells into the hippocampus of rat AD models. In vitro experimentation showed that 10−5 M ASI induced NSCs to differentiate into β-tubulin III+ and GFAP+ cells. NSCs transplantation into rat AD models resulted in improvements in learning and memory, especially in the ASI-treated groups. ASI treatment resulted in an increase in the number of β-tubulin III+ cells in the hippocampus. Further investigation showed that ASI inhibited PS1 expression in vitro and in vivo. The high-dose ASI downregulated the Notch intracellular domain, whereas the low-dose ASI increased Notch-1 and NICD. In conclusion, ASI treatment resulted in improvements in learning and memory of AD models by promoting NSC proliferation and differentiation partly through the Notch signal pathway.

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

“…NSCs were cultured in Neurobasal medium supplemented with 2% B27, 1% N2, 2% Gln, 20 ng/ml recombinant murine epidermal growth factor (EGF, Peprotech, Cat# 315-09), and 20 ng/ml recombinant murine fibroblast growth-basic factor (FGF, Peprotech, Cat# 450-33) for 7-10 days (Homayouni-Moghadam et al, 2018). To observe NSCs proliferation under different conditions, recombinant mouse IL-17A (IL-17A, Novoprotein, Shanghai, China, Cat# CX14) 1 ng/ ml, recombinant mouse IL-17F (IL-17F, Novoprotein, Shanghai, China, Cat# CC11) 1 ng/ml, 100 nM As IV (Haiyan et al, 2016;Wang et al, 2020), or the 5 ml/ml PLDK CMV G&PR U6 Wnt2 virus (Wnt2, Neuron biotech, Lenti-3206-GR749) (Williams et al, 2016) were used, according to the product introduction. The morphology and growth feature of the NSCs were observed and taken pictures by inverted microscope after 3 days' treatment, and collected for immunochemistry staining and western blots.…”

Analysis of the influence of inoculation of ischiatic nerve fragments in the presence of astragalosíde ivin the neuroprotection of dorsal root ganglions in animals submitted to the transcription of the spinal cord

“…Cells were treated and transplanted into the hippocampus of AD rat mice. In vitro, it was shown that 10-5 AS-IV induced NSCs to differentiate into GFAP and β-tubulin III, a marker that is related to microtubule formation and neuron structure (Haiyan et al, 2016) . Therefore, in agreement our findings also allowed us to observe increase of cells expressing GFAP superior to the untreated groups and we performed analysis of a specific marker that regulates the synaptic transmission and plasticity, the GAP-43, indicating that the AS-IV acts in the maintenance of plasticity mechanisms.…”

Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known Chinese Tonic

“…The neural stem cell (NSC) transplantation is a potential therapeutic approach for AD. In an AD model transplanted with NSC into the hippocampus, AST-IV increased the proliferation of NSC and immature neurons and promoted the learning and memory by up-regulating Notch-1 and down-regulating presenilin-1 (PS-1) [ 108 ].…”