Asian Journal
Of Traditional Medicines

Abstract: Glioma is a common primary intracranial tumor with high mortality and postoperative recurrence. Developing efficient therapies with lower toxicity is urgently needed. Sophora flavescens (SF) is a common Chinese medicine used to treat eczema, wet ulcers and itchy skin. Modern pharmacological studies have showed that SF has anti-glioma effects, but the mechanism of action remains unclear. This study aims to reveal the pharmacological mechanism of SF in treating glioma. The active components and related targets of SF were obtained from TCMSP. Genecard and Online Mendelian Inheritance in Man (OMIM) databases were used to explore the therapeutic targets for glioma. By making Venn diagram, we obtained 132 common targets of compounds and diseases. STRING databases and Cytoscape were used to construct diagrams of Protein-Protein Interaction (PPI) networks. Through the construction of PPI network, potential targets with degree value greater than the median were taken as core targets
for further analysis. A total of 66 core targets were screened out. The degree values of TP53, HSP90AA1, MAPK1, and AKT1 were higher, indicating that these genes played important roles in this network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to further discover the mechanism of active components in SF. Through enrichment analysis, it was found that the core targets were mainly enriched in PI3K/AKT signaling pathway, cell senescence related signaling pathway and IL-17 signaling pathway. In order to further explore the binding between active components and selected target, molecular docking was carried out. Finally, SwissADME was used to determine whether the compound could cross the blood-brain barrier. Based on network pharmacology, we speculated that matrine and formononetin in SF might inhibit PI3K/AKT signaling pathway and cellular senescence related signaling pathway by targeting AKT1, TP53,
MAPK1 and other key targets. In summary, this study preliminarily explored the target and mode of action of SF in the treatment of glioma, laying the foundation for further research on its mechanism.

Key words: network pharmacology, Sophora flavescens, glioma, PI3K/AKT signaling pathway, AKT1