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

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Ginsenoside RK3 promotes neurogenesis in Alzheimer's disease through activation of the CREB/BDNF pathway
Journal of Ethnopharmacology ( IF 4.8 ) Pub Date : 2023-11-18 , DOI: 10.1016/j.jep.2023.117462
Lingyu She ₁ , Hao Tang ₂ , Yuqing Zeng ₂ , Liwei Li ₂ , Li Xiong ₃ , Jinfeng Sun ₄ , Fan Chen ₃ , Juan Ren ₃ , Jing Zhang ₂ , Wei Wang ₅ , Xia Zhao ₆ , Guang Liang ₂

Affiliation

Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, Jilin, 133002, China; Affiliated Yongkang First People's Hospital and School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, 311399, China.
Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.
Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.
Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, Jilin, 133002, China; Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.
Affiliated Yongkang First People's Hospital and School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, 311399, China.
Affiliated Yongkang First People's Hospital and School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, 311399, China; Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.

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 role of RK3 on neurogenesis was combined with the activation of CREB/BDNF pathway. Inhibition of CREB/BDNF pathway attenuated the effect of RK3.

Conclusion

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).

中文翻译：

人参皂苷 RK3 通过激活 CREB/BDNF 通路促进阿尔茨海默病的神经发生

民族药理学相关性

在古书《神农本草经》中，人参被认为具有安神、改善认知功能、延年益寿等多种功效。人参皂苷是人参的主要活性成分。人参皂苷RK3（RK3）是一种从人参中提取的稀有人参皂苷，具有很强的药理潜力。然而，其对神经发生的影响尚未得到充分研究。

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记忆，并探讨RK3的作用机制。

材料和方法

通过莫里斯水迷宫（MWM）和新物体识别测试（NORT）确定RK3对学习和记忆的治疗效果。通过免疫荧光和蛋白质印迹检测RK3的发病机制和对原代神经元和动物模型的保护作用。采用蛋白质印迹法检测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 促进小鼠海马神经发生和突触发生。在体外，RK3 可防止原代培养的神经元中 Aβ 诱导的损伤，并促进 PC12 的增殖以及突触相关蛋白的表达。从机制上来说，RK3 对神经发生的积极作用与 CREB/BDNF 通路的激活相结合。 CREB/BDNF 通路的抑制减弱了 RK3 的作用。