Sanshen San Formula Hinders Cognitive Function and Pathology in Alzheimer's Disease Through Potentiating the Function of Synapse

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-04-09 DOI:10.1111/cns.70349

Shiquan Chang, Nana Ding, Yalin Li, Ying Li, Ziling Tang, Junping Pan, Li Yan, Jiaxu Chen

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Abstract

Background

Alzheimer's disease (AD) constitutes a devastating neurodegenerative disorder, manifested by amyloid-β aggregation, phosphorylated tau accumulation, and progressive cognitive deterioration. Current therapeutic interventions remain predominantly symptomatic, underscoring the urgency for more efficacious treatment strategies.

Purpose

This study elucidated the therapeutic potential of Sanshen San (SSS), a traditional Chinese herbal formula encompassing Polygala Radix, Pini Radix in Poria, and Acori Tatarinowii Rhizoma, on cognitive function and AD pathology.

Methods

We implemented both acute Aβ_1-42-injected mice and 5xFAD transgenic mouse models. The therapeutic efficacy of SSS was assessed through behavioral paradigms including Y-maze, Novel Object Recognition, and Morris Water Maze. Molecular mechanisms were delineated utilizing RNA sequencing, metabolomics analysis, immunofluorescence staining, Golgi-Cox staining, transmission electron microscopy, and Western blotting.

Results

Chemical analysis unveiled 10 principal bioactive compounds in SSS. The formula substantially ameliorated cognitive performance in both Aβ_1-42-injected and 5xFAD mouse models, attenuated Aβ plaque burden, and augmented microglial phagocytosis. SSS safeguarded synaptic integrity, enhanced mitochondrial function, and facilitated autophagy. Transcriptomic and metabolomic analyses demonstrated that SSS predominantly operates by reinstating synaptic transmission and neurotransmitter function, particularly in the dopaminergic system.

Conclusion

SSS efficaciously mitigates AD pathology through potentiating synaptic function, optimizing mitochondrial homeostasis, and restoring neurotransmitter balance, exemplifying a promising multi-target therapeutic strategy for the treatment of AD.

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三神散方通过增强突触功能对阿尔茨海默病认知功能和病理的影响

阿尔茨海默病（AD）是一种破坏性的神经退行性疾病，表现为淀粉样蛋白-β聚集、磷酸化tau蛋白积累和进行性认知衰退。目前的治疗干预措施仍然主要是对症治疗，这强调了迫切需要更有效的治疗策略。目的研究中药复方三神散（SSS）对认知功能和AD病理的治疗作用。三神散是一种由茯苓、茯苓、石菖蒲组成的中药复方。方法采用急性a β1-42注射小鼠和5xFAD转基因小鼠模型。通过y型迷宫、新物体识别和Morris水迷宫等行为范式评估SSS的治疗效果。利用RNA测序、代谢组学分析、免疫荧光染色、高尔基-考克斯染色、透射电镜和Western blotting来描述分子机制。结果化学分析揭示了SSS中10种主要的生物活性化合物。该配方显著改善了注射Aβ1-42和5xFAD小鼠模型的认知能力，减轻了Aβ斑块负担，增强了小胶质细胞吞噬。SSS保护突触完整性，增强线粒体功能，促进自噬。转录组学和代谢组学分析表明，SSS主要通过恢复突触传递和神经递质功能，特别是在多巴胺能系统中起作用。结论SSS通过增强突触功能、优化线粒体稳态和恢复神经递质平衡，有效减轻AD病理，是一种有前景的多靶点治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.