Exploring the therapeutic potential of Astragalin in Parkinson’s disease: a network pharmacology approach
TL;DR
This study provides comprehensive evidence that AST may alleviate symptoms associated with PD by modulating the IL-17 signaling pathway and highlights the potential of AST as a novel treatment for PD.
Abstract
Background/objectives: Parkinson’s disease (PD) is a neurodegenerative disorder with limited treatment options. This study investigated the therapeutic potential of astragalin (AST) in PD and explored its underlying mechanisms. Methods: Network pharmacology identified nine overlapping genes between the AST and PD target sets. Protein-protein interaction networks were constructed using Cytoscape and STRING. Based on KEGG pathway analysis, AST may influence PD through the IL-17 signaling pathway. Molecular docking simulations demonstrated a strong binding affinity between AST and key target proteins. In vitro, various concentrations of AST were applied to SH-SY5Y cells, and cell viability and inflammation-related factors were assessed using Cell Counting Kit-8 assays, RT-qPCR, immunoblotting, and enzyme-linked immunosorbent assay. In vivo, mice received intraperitoneal injections of AST, followed by behavioral assessments to evaluate AST's effects on PD symptoms. Results: Nine overlapping genes were identified. Molecular docking analyses revealed robust binding interactions between AST and PTGS2, PRSS1, PRKACA, and PIK3CG. In vitro results indicated that 40 μM and 60 μM concentrations of AST partially mitigated MPP+-induced cytotoxicity and morphological damage. Furthermore, treatment with AST led to a reduction in inflammatory factor expression while inhibiting IKKα/IκBα/p65 phosphorylation. In vivo experiments demonstrated that AST improved motor function and ameliorated cognitive impairments induced by MPTP administration, while enhancing tyrosine hydroxylase protein expression without causing significant organ damage. Conclusions: This study provides comprehensive evidence that AST may alleviate symptoms associated with PD by modulating the IL-17 signaling pathway. These findings highlight the potential of AST as a novel treatment for PD. Graphical abstract: Graphical abstract available at: https://links.lww.com/MS9/B316.