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

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

  • Neuropharmacology. 2025 Aug 28:110661. doi: 10.1016/j.neuropharm.2025.110661.
Lianmei Liu 1,  Zhixin Li 1,  Xuemei Qin 2,  Lei Xu 3,  Zhenyu Li 4,  Shengnan Xiao 5
Affiliations

Affiliations

  • 1 Institute of Taihang Materia Medica, Shanxi University of Chinese Medicine, Jinzhong, 030600, China.
  • 2 Institute of Taihang Materia Medica, Shanxi University of Chinese Medicine, Jinzhong, 030600, China; Modern Research Center for Traditional Chinese Medicine of Shanxi University, NO.92, Wucheng Road, Taiyuan 030006, China.
  • 3 Institute of Taihang Materia Medica, Shanxi University of Chinese Medicine, Jinzhong, 030600, China. Electronic address: 18246691730@163.com.
  • 4 Institute of Taihang Materia Medica, Shanxi University of Chinese Medicine, Jinzhong, 030600, China; Modern Research Center for Traditional Chinese Medicine of Shanxi University, NO.92, Wucheng Road, Taiyuan 030006, China. Electronic address: lizhenyu@sxu.edu.cn.
  • 5 Institute of Taihang Materia Medica, Shanxi University of Chinese Medicine, Jinzhong, 030600, China. Electronic address: 869086406@qq.com.
PMID: 40882598 DOI: 10.1016/j.neuropharm.2025.110661
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.

Keywords

Astragaloside Ⅳ; Multi omics analysis; Neuroinflammation; PI3K-AKT pathway; Parkinson's Disease.

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