Systematic elucidation of the pharmacological mechanisms of Rhynchophylline for treating epilepsy via network pharmacology

BACKGROUND: Epilepsy, one of the most common neurological disorders, affects over 70 million people worldwide. Rhynchophylline displays a wide variety of pharmacologic actives. However, the pharmacologic effects of rhynchophylline and its mechanisms against epilepsy have not been systematically elucidated. METHODS: The oral bioavailability and druglikeness of rhynchophylline were evaluated using the Traditional Chinese Medicine Systems Pharmacology Database. Rhynchophylline target genes to treat epilepsy were identified using PharmMapper, SwissTargetPrediction and DrugBank databases integration. Protein-protein interaction analysis was carried out by utilizing the GeneMANIA database. WebGestalt was employed to perform Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The drug-disease-target-Gene Ontology-pathway network was constructed using Cytoscape. RESULTS: The oral bioavailability and druglikeness of rhynchophylline were calculated to be 41.82% and 0.57, respectively. A total of 20 rhynchophylline target genes related to epilepsy were chosen. Among the 20 genes and their interacting genes, 54.00% shared protein domains and 16.61% displayed co-expression characteristics. Gene ontology, Kyoto Encyclopedia of Genes and Genomes and network analyses illustrate that these targets were significantly enriched in regulation of sensory perception, morphine addiction, neuroactive ligand-receptor interaction and other pathways or biological processes. CONCLUSION: In short, rhynchophylline targets multiple genes or proteins, biological processes and pathways. It shapes a multiple-layer network that exerts systematic pharmacologic activities on epilepsy.