Ginsenoside RK3 promotes neurogenesis in Alzheimer's disease through activation of the CREB/BDNF pathway

作者：Lingyu She, Hao Tang, Yuqing Zeng, Liwei Li, Xiong Li, Jinfeng Sun, Fan Chen, Juan Ren, Jing Zhang, Wei Wang, Xia Zhao, Guang Liang · 发表于：Journal of Ethnopharmacology · 年份：2023 · DOI：10.1016/j.jep.2023.117462 · 被引用次数：28 · 研究领域：Neurological Disease Mechanisms and Treatments、Ginseng Biological Effects and Applications、Fibroblast Growth Factor Research

ETHNOPHARMACOLOGICAL RELEVANCE: In the ancient book "Shen Nong's Herbal Classic," Panax ginseng CA Mey was believed to have multiple benefits, including calming nerves, improving cognitive function, and promoting longevity. Ginsenosides are the main active ingredients of ginseng. Ginsenoside RK3 (RK3), a rare ginsenoside extracted from ginseng, displays strong pharmacological potential. However, its effect on neurogenesis remains insufficiently investigated. AIM OF THE STUDY: This study aims to investigate whether RK3 improves learning and memory by promoting neurogenesis, and to explore the mechanism of RK3 action. MATERIALS AND METHODS: The therapeutic effect of RK3 on learning and memory was determined by the Morris water maze (MWM) and novel object recognition test (NORT). The pathogenesis and protective effect of RK3 on primary neurons and animal models were detected by immunofluorescence and western blotting. Protein expression of cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway was detected by western blotting. RESULTS: Our results showed that RK3 treatment significantly improved cognitive function in APPswe/PSEN1dE9 (APP/PS1) mice and C57BL/6 (C57) mice. RK3 promotes neurogenesis and synaptogenesis in the mouse hippocampus. In vitro, RK3 prevents Aβ-induced injury in primary cultured neurons and promotes the proliferation of PC12 as well as the expression of synapse-associated proteins. Mechanically, the positve r...