Exploring the Anti-Glioma Mechanisms of Oridonin: Network Pharmacology and Experimental Insights into EMT Pathways.

Introduction: Gliomas are aggressive brain tumors with a poor prognosis and high recurrence. Oridonin, a traditional Chinese medicine, has shown potential in treating various cancers, but its role in glioma treatment, especially in modulating Epithelial- Mesenchymal Transition (EMT), remains underexplored.

Methods: We identified 371 potential target genes of Oridonin using various bioinformatics databases. Enrichment analyses, including Differential Expression Analysis, Gene Set Enrichment Analysis (GSEA), and Weighted Gene Co-expression Network Analysis (WGCNA), were performed to link these targets to glioma characteristics. in vitro experiments validated Oridonin's impact on EMT-related gene expression in glioma cells.

Results: Enrichment analyses identified 19 common genes between Oridonin and glioma targets, with 12 EMT-related core genes. KEGG enrichment highlighted PI3K-Akt, MAPK pathways, and glioma pathways, while DO enrichment included high-grade gliomas. CCK8 assay showed Oridonin IC50 values of 6.92 μM for H4 and 10.54 μM for SW1783 glioma cell lines. WB results indicated increased E-Cadherin and decreased Vimentin, N-Cadherin, and Snail expression after Oridonin treatment. PPI network and single- cell transcriptome analyses identified key genes linked to glioma progression and immune cell infiltration.

Discussion: Oridonin may inhibit glioma progression by targeting EMT-related pathways like PI3K-Akt and MAPK. The upregulation of E-Cadherin and downregulation of Vimentin, N-Cadherin, and Snail suggest a reversal of the EMT process. Future work should validate these effects in vivo and explore Oridonin's ability to cross the blood- -brain barrier.

Conclusion: Oridonin may provide a novel therapeutic approach for glioma by targeting EMT-related pathways, offering a foundation for further clinical investigation.