Elucidating Astragaloside IV's Anti-Glioma Action via Network Pharmacology, Molecular Docking, and Experimental Evidence for PI3K/AKT Pathway Inhibition

Objective: To investigate astragaloside IV's (AS-IV) anti-glioma effects and mechanisms. Methods: Potential AS-IV targets were screened using SwissTarget, Super PRED, and PharmMapper databases. Glioma-related targets were identified from GeneCards, OMIM, and TTD. Intersection genes underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Anti-glioma mechanisms were investigated using A172 and U251 glioma cell lines. Cells were treated with AS-IV at 20, 30, or 50 mg/mL. MTT assessed proliferation. Cell scratch and transwell assays evaluated invasion. Flow cytometry analyzed cell cycle distribution and apoptosis. Western blot measured expression of cell cycle, apoptosis, epithelial-mesenchymal transition, and PI3K-AKT pathway-related genes. Results: Network pharmacology and molecular docking predicted AS-IV anti-glioma targets were associated with the PI3K/AKT pathway. AS-IV inhibited A172 and U251 cell proliferation and invasion dose- and time-dependently. It arrested the cell cycle in G0/G1 phase and induced apoptosis. AS-IV upregulated P21, Bax, and E-cadherin expression while downregulating CDK4, CDK6, Bcl-2, Vimentin, P-PI3K, and P-AKT. Conclusion: AS-IV exhibits anti-tumor effects against glioma cells, potentially by inhibiting the PI3K/AKT signaling pathway. This leads to apoptosis induction, proliferation suppression, cell cycle arrest, and invasion inhibition.