Tenuigenin ameliorates cognitive dysfunction in Alzheimer’s disease via hippocampal neurogenesis enhancement

A promising strategy for treating Alzheimer’s disease (AD) is hippocampal neurogenesis enhancement. Tenuigenin (TEN) is a bioactive compound extracted from Polygala tenuifolia that is widely used for treating amnesia in Chinese medicine. However, whether TEN is effective in treating AD through hippocampal neurogenesis is not fully clear. This study aimed to explore the pharmacologic effect and underlying mechanism of TEN on hippocampal neurogenesis and cognitive deficit amelioration in AD. In an in vivo study, TEN administration significantly ameliorated the cognitive decline in APP/PS1 transgenic AD mice via enhancement of hippocampal neurogenesis, which might be attributed to activation of the GSK-3β/β-catenin pathway. Furthermore, an in silico study suggested that TEN might be directly targeted to GSK-3β. Overall, TEN enhanced hippocampal neurogenesis and consequently ameliorated cognitive deficits via GSK-3β/β-catenin pathway activation, indicating that TEN might be a promising novel agent for AD treatment.