4.7 Article

Icarisid II promotes proliferation and neuronal differentiation of neural stem cells via activating Wnt/β-catenin signaling pathway

期刊

PHYTOTHERAPY RESEARCH
卷 35, 期 5, 页码 2773-2784

出版社

WILEY
DOI: 10.1002/ptr.7022

关键词

Alzheimer's disease; differentiation; icarisid II; neural stem cell; proliferation; Wnt/beta-catenin signaling pathway

资金

  1. Department of Education of Liaoning Province [L201945, L202036]

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Adult neurogenesis is crucial for cognitive function maintenance in mammals and humans, and it is seen as a potential therapeutic strategy for neurodegenerative diseases like Alzheimer's disease. Icarisid II (ICS II), derived from Epimedii Folium, has been shown to have neuroprotective effects, including promoting proliferation and differentiation of neural stem cells (NSCs). The study demonstrates that ICS II promotes NSCs proliferation and neuronal differentiation by activating the Wnt/beta-catenin signaling pathway.
Adult neurogenesis plays a vital role in maintaining cognitive functions in mammals and human beings. Mobilization of hippocampal neurogenesis has been regarded as a promising therapeutic approach to restore injured neurons in neurodegenerative diseases including Alzheimer's disease (AD). Icarisid II (ICS II), an active ingredient derived from Epimedii Folium, has been reported to exhibit multiple neuroprotective effects. In the present study, we investigated the effects of ICS II on the proliferation and differentiation of neural stem cells (NSCs) and amyloid precusor protein (APP)-overexpressing NSCs (APP-NSCs) in vitro. Our results demonstrated that ICS II dose-dependently suppressed apoptosis and elevated viability of APP-NSCs. ICS II (1 mu M) potently promoted proliferation and neuronal differentiation of NSCs and APP-NSCs. ICS II (1 mu M) significantly upregulated Wnt-3a expression, increased the phosphorylation of glycogen synthase kinase-3 beta and enhanced the nuclear transfer of beta-catenin. Moreover, ICS II also promoted astrocytes to secrete Wnt-3a, which positively modulates Wnt/beta-catenin signaling pathway. These findings demonstrate that ICS II promotes NSCs proliferation and neuronal differentiation partly by activating the Wnt/beta-catenin signaling pathway.

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