Ginkgo biloba Extract GBE50 ameliorates cerebrovascular dysfunction and cognitive impairment in a mouse model of Alzheimer's disease

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-03-19 DOI:10.1016/j.phymed.2025.156646

Ting Yu , Zijie Wei , Jing Wang , Chenghuan Song , Wanying Huang , Pingao Zhang , Jiyun Shi , Rui Zhang , Meifang Jiang , Dandan Wang , Yongfang Zhang , Hongzhuan Chen , Hao Wang

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引用次数: 0

Abstract

Background

Alzheimer's disease (AD) is a complex neurodegenerative disorder in which neurovascular unit (NVU) dysfunction plays a critical role. GBE50, a refined extract of Ginkgo biloba containing over 50 % total flavonoids and terpene lactones, is widely used in the clinical prevention and treatment of cardiovascular and cerebrovascular diseases due to its anti-platelet aggregation, anti-inflammatory, and antioxidant properties. However, its specific effects on NVU integrity and cerebrovascular function in AD remain unclear.

Purpose

This study aims to investigate the therapeutic effects of GBE50 on NVU integrity and cognitive impairment in an AD mouse model.

Methods

APP/PS1 transgenic mice were treated with GBE50 via intragastric administration for 10 weeks. Cognitive performance was assessed through behavioral tests, while the structural and functional integrity of the NVU was evaluated using immunofluorescence, laser speckle imaging, and in vivo multi-photon imaging. Furthermore, target prediction and transcriptomic analyses were conducted to uncover potential molecular mechanisms and identify specific targets of GBE50.

Results

GBE50 treatment significantly alleviated cognitive deficits in APP/PS1 mice. It enhanced cerebrovascular structure and function by increasing vessel density, diameter, and branching, leading to improved cerebral blood flow (CBF). GBE50 also restored NVU components such as endothelial cells, astrocytes, and pericytes, promoted parenchyma and perivascular Aβ clearance, and reduced neuroinflammation. Bioinformatics and transcriptomic analyses revealed that GBE50 exerted its effects by regulating pathways related to vascular repair, neuroprotection, and Aβ clearance.

Conclusion

The findings demonstrate that GBE50 improves cognitive dysfunction in AD by restoring NVU integrity and cerebrovascular function through multi-target mechanisms. This study highlights the potential of GBE50 as a promising therapeutic approach for AD and other neurodegenerative diseases involved in cerebrovascular dysfunction.

Abstract Image

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银杏叶提取物GBE50改善阿尔茨海默病小鼠模型的脑血管功能障碍和认知障碍

阿尔茨海默病（AD）是一种复杂的神经退行性疾病，其中神经血管单元（NVU）功能障碍起着关键作用。GBE50是银杏总黄酮和萜烯内酯含量超过50%的精制提取物，具有抗血小板聚集、抗炎、抗氧化等作用，广泛应用于临床防治心脑血管疾病。然而，其对AD患者NVU完整性和脑血管功能的具体影响尚不清楚。目的探讨GBE50对AD小鼠NVU完整性和认知功能障碍的治疗作用。方法GBE50灌胃治疗sapp /PS1转基因小鼠10周。通过行为测试评估认知能力，而使用免疫荧光、激光散斑成像和体内多光子成像评估NVU的结构和功能完整性。此外，我们还进行了靶标预测和转录组学分析，以揭示GBE50的潜在分子机制并确定其特异性靶标。结果gbe50治疗可显著减轻APP/PS1小鼠的认知缺陷。它通过增加血管密度、直径和分支来增强脑血管结构和功能，从而改善脑血流（CBF）。GBE50还能恢复NVU成分，如内皮细胞、星形胶质细胞和周细胞，促进实质和血管周围Aβ清除，减少神经炎症。生物信息学和转录组学分析显示，GBE50通过调节与血管修复、神经保护和Aβ清除相关的途径发挥作用。结论GBE50可通过多靶点机制改善AD患者认知功能障碍，恢复NVU完整性和脑血管功能。这项研究强调了GBE50作为一种有希望的治疗AD和其他涉及脑血管功能障碍的神经退行性疾病的方法的潜力。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.