银杏叶提取物761通过调节Wnt/β-连环蛋白信号通路诱导海马神经元细胞凋亡和自噬来抑制血管性痴呆。

EGb761 suppressed vascular dementia via modulating Wnt/β-catenin signaling pathway-induced apoptosis and autophagy in hippocampal neuronal cells.

作者信息

Yin Nan, Tang Zhipeng, Yang Yanyan, Li Xiuqin, Duan Ruisheng, Xu Guodong, Lv Peiyuan

机构信息

Department of Neurology, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang City, Hebei Province, 050017, People's Republic of China.

Department of Neurology, Hebei General Hospital, No. 348 Heping West Road, Shijiazhuang City, Hebei Province, 050051, People's Republic of China.

出版信息

Eur J Med Res. 2025 Jun 19;30(1):497. doi: 10.1186/s40001-025-02681-6.

DOI:10.1186/s40001-025-02681-6

PMID:40537804

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12178017/

Abstract

OBJECTIVES

The study aimed to explore the effects of EGb761 on vascular dementia (VD) rats and the mechanisms of action.

METHODS

The Morris water maze test was utilized to assess the spatial learning and memory abilities of the rats; Hematoxylin and Eosin (HE) staining and electron microscopy were used to observe changes in hippocampal neuron cells; Immunohistochemistry was performed to detect the expression of cleaved caspase-3 and microtubule-associated proteins light chain 3 (LC3-II) positive cells in hippocampal neurons; immunofluorescence staining was carried out to determine the immunofluorescence intensity of IRGM in hippocampal neurons; western blotting was used to measure the expression of related proteins.

RESULTS

EGb761 significantly improved the cognitive function of vascular dementia rats (P < 0.01) and reduced the apoptosis of hippocampal neurons.Furthermore, EGb761 suppressed ROS, thereby promoting the expression of proteins related to the Wnt/β-catenin signaling pathway and inhibiting the expression of C-Jun N-terminal Kinase (p-JNK), c-Jun N-terminal kinase (p-c-JUN), Protein 53 (P53), immunity-related GTPase M (IRGM), Transcription Factor EB (TFEB), microtubule-associated proteins light chain 3 (LC3), Lysosomal Associated Membrane Protein 1 (LAMP1), and Sequestosome 1 (SQSTM1).

CONCLUSIONS

Ginkgo Biloba Extract 761 (EGb761) mediated the Wnt/β-catenin signaling pathway to inhibit apoptosis and autophagy in hippocampal neurons in VD rats.

摘要

目的

本研究旨在探讨银杏叶提取物761（EGb761）对血管性痴呆（VD）大鼠的影响及其作用机制。

方法

采用Morris水迷宫试验评估大鼠的空间学习和记忆能力；用苏木精-伊红（HE）染色和电子显微镜观察海马神经元细胞的变化；进行免疫组织化学检测海马神经元中裂解的半胱天冬酶-3和微管相关蛋白轻链3（LC3-II）阳性细胞的表达；进行免疫荧光染色以确定海马神经元中免疫相关鸟苷三磷酸酶M（IRGM）的免疫荧光强度；用蛋白质免疫印迹法检测相关蛋白的表达。

结果

EGb761显著改善血管性痴呆大鼠的认知功能（P<0.01），并减少海马神经元的凋亡。此外，EGb761抑制活性氧，从而促进Wnt/β-连环蛋白信号通路相关蛋白的表达，并抑制c-Jun氨基末端激酶（p-JNK）、c-Jun氨基末端激酶（p-c-JUN）、蛋白质53（P53）、免疫相关鸟苷三磷酸酶M（IRGM）、转录因子EB（TFEB）、微管相关蛋白轻链3（LC3）、溶酶体相关膜蛋白1（LAMP1）和聚集体蛋白1（SQSTM1）的表达。