Astragaloside Ⅳ improves neuroinflammation in Parkinson's disease by regulating amino acid metabolism and the PI3K-AKT signaling pathway

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-08-28 DOI:10.1016/j.neuropharm.2025.110661

Lianmei Liu , Zhixin Li , Xuemei Qin , Lei Xu , Zhenyu Li , Shengnan Xiao

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Abstract

Objective

Elucidation the pharmacological mechanism of AS-Ⅳ, providing a scientific basis for the development of AS-Ⅳ as a therapeutic agent for Parkinson's disease (PD).

Methods

An acute PD model was established in C57BL/6 mice through intraperitoneal injection of MPTP. A comprehensive multi-omics approach was employed for in-depth data analysis and processing. The effects of AS-Ⅳ on motor dysfunction and neuropathological changes were validated at both protein and mRNA levels using Western blotting and RT-qPCR, revealing its therapeutic potential and mechanisms of action in PD.

Results

AS-Ⅳ significantly improved behavioral parameters in PD mouse models, increased the population of dopaminergic neurons, and attenuated neuroinflammation. Metabolomic analysis revealed that AS-Ⅳ exerts anti-neuroinflammatory effects through modulation of amino acid metabolism. Further investigation demonstrated that AS-Ⅳ downregulates CCN3 gene expression, thereby enhancing PI3K-AKT phosphorylation and suppressing the expression of inflammatory factors.

Conclusions

In summary, this study elucidates a novel mechanism of AS-Ⅳ in PD treatment, providing a scientific foundation for the development of AS-Ⅳ drugs for PD.

Abstract Image

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黄芪甲苷Ⅳ通过调节氨基酸代谢和PI3K-AKT信号通路改善帕金森病的神经炎症

目的阐明AS-Ⅳ的药理作用机制，为AS-Ⅳ作为帕金森病（PD）治疗剂的开发提供科学依据。方法通过腹腔注射MPTP建立C57BL/6小鼠急性PD模型。采用综合多组学方法对数据进行深入分析和处理。通过Western blotting和RT-qPCR在蛋白和mRNA水平上验证AS-Ⅳ对运动功能障碍和神经病理改变的影响，揭示其在PD中的治疗潜力和作用机制。结果as -Ⅳ可显著改善PD小鼠模型的行为参数，增加多巴胺能神经元的数量，减轻神经炎症。代谢组学分析显示AS-Ⅳ通过调节氨基酸代谢发挥抗神经炎症作用。进一步研究发现AS-Ⅳ下调CCN3基因表达，从而增强PI3K-AKT磷酸化，抑制炎症因子的表达。综上所述，本研究阐明了AS-Ⅳ在PD治疗中的新机制，为开发AS-Ⅳ治疗PD的药物提供了科学依据。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).