背景:在古书《神农草药经典》中,\“人参CAMey被认为有多种好处,包括镇静神经,改善认知功能,促进长寿。人参皂苷是人参的主要活性成份。人参皂苷RK3(RK3),一种从人参中提取的稀有人参皂苷,显示强大的药理潜力。此外,其对神经发生的影响仍未得到充分研究。
目的:本研究旨在探讨RK3是否通过促进神经发生来改善学习和记忆,并探讨RK3的作用机制。
方法:通过Morris水迷宫(MWM)和新物体识别测试(NORT)确定RK3对学习和记忆的治疗作用。免疫荧光和免疫印迹法检测RK3对原代神经元和动物模型的发病机制和保护作用。免疫印迹法检测cAMP反应元件结合蛋白(CREB)-脑源性神经营养因子(BDNF)信号通路的蛋白表达。
结果:我们的结果表明,RK3治疗显着改善了APPswe/PSEN1dE9(APP/PS1)小鼠和C57BL/6(C57)小鼠的认知功能。RK3促进小鼠海马中的神经发生和突触发生。体外,RK3可防止Aβ诱导的原代神经元损伤,并促进PC12的增殖以及突触相关蛋白的表达。机械上,RK3通过CREB-BDNF途径在体内和体外发挥积极作用。
结论:结论:本研究表明,RK3通过CREB-BDNF信号通路促进神经发生和突触发生,促进APP/PS1和C57小鼠的学习和认知。因此,RK3有望进一步发展成为治疗阿尔茨海默病(AD)的潜在候选药物。
BACKGROUND: 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.
OBJECTIVE: This study aims to investigate whether RK3 improves learning and memory by promoting neurogenesis, and to explore the mechanism of RK3 action.
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 role of RK3 on neurogenesis was combined with the activation of CREB/BDNF pathway. Inhibition of CREB/BDNF pathway attenuated the effect of RK3.
CONCLUSIONS: In conclusion, this study demonstrated that RK3 promotes learning and cognition in APP/PS1 and C57 mice by promoting neurogenesis and
synaptogenesis through the CREB/BDNF signaling pathway. Therefore, RK3 is expected to be further developed into a potential drug candidate for the treatment of Alzheimer\'s disease (AD).