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

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.

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.

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.

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.

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