Abstract
BACKGROUND: Semen strychni is commonly used to treat gliomas in China. However, the underlying mechanism of action of semen strychni in glioma treatment remains unknown. Using network pharmacology and molecular docking, we investigated the probable pharmacological mechanisms of semen strychni in glioma treatment. METHODS: The active components of semen strychni were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. Using the Cytoscape program created the active component-target network diagram of semen strychni. The GeneCards, DisGeNET, and Online Mendelian Inheritance in Man databases were used to compile the list of targets related to glioma. Using the STRING database created a protein-protein interaction network of popular drugs and disease targets. For Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis of common targets, the Database for Annotation, Visualization and Integrated Discovery database was utilized. In order to identify the main targets of semen strychni in the treatment of glioma, a target-pathway interaction network was built. The molecular docking of critical and crucial components was done using AutoDock. Glioma samples from the Cancer Genome Atlas and Human Protein Atls databases were extracted to detect the mRNA and protein expression levels of ADRB1 and ADRB2 and analyze the correlation between expression and survival of glioma patients. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, Transwell, and wound healing assays validate the effect of stigmasterol on the malignant progression of glioma cells. RESULTS: The core components of semen strychni used in the treatment of glioma included stigmasterol, (S)-stylopine, isobrucine, icaride A, and isostrychnine N-oxide (I), which may operate on core targets such as ADRB1, ADRB2, CHRM3, ADRA1A, and ESR1. The significant pathways discovered using Kyoto Encyclopedia of Genes and Genomes enrichment analysis were chemical carcinogenesis-receptor activation, calcium signaling pathway, and pathways in cancer. The outcomes of the molecular docking demonstrated a strong affinity between the central targets and elements. Data from the Cancer Genome Atlas and Human Protein Atls databases indicate that ADRB1 and ADRB2 are expressed in glioma, and high expression of ADRB2 may predict a good outcome. In vitro experimental results indicate that stigmasterol can inhibit the malignant progression of U251 cells. CONCLUSION: This article discusses the probable mechanism of action of semen strychni in the treatment of glioma, which can serve as a theoretical basis and evidence for subsequent experimental investigations.