To explore the mechanism of Arisaema cum Bile on epilepsy based on network pharmacology and experimental verification

This study aims to explore the mechanism of Arisaema cum Bile on epilepsy using combination of network pharmacology and patch clamp recording. Active ingredients of Arisaema cum Bile were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literatures. Epilepsy-related targets were identified from GeneCards and OMIM database. STRING platform was employed to perform protein-protein interaction (PPI), and David platform was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis. The drug-ingredient-target-pathway-disease network was constructed with Cytoscape software. The animal experiments were approved by the Laboratory Animal Ethical and Welfare Committee Hebei Medical University. Nine compounds were detected as the active ingredients of Arisaema cum Bile, including chenodeoxycholic acid (CDCA), deoxycholic acid and β-sitosterol, etc. A total of 22 key potential targets were identified, including 5-hydroxytryptamine transporter (SLC6A4), gamma-aminobutyric acid receptor type A subunit alpha 2 (GABRA2) and neuronal acetylcholine receptor subunit alpha-7 (CHRNA7). These targets were associated with biological processes of serotonergic synapse, GABAergic synapse and ion transmembrane transport. Brain slice electrophysiology experiments revealed that β-sitosterol and CDCA inhibited the action potential (AP) of CA1 pyramidal neurons in the mouse hippocampus. Both β-sitosterol and CDCA affected the properties of AP, such as rheobase, delay and depolarization duration. In addition, the inhibitory effect of AP was more prominent when the two compounds were given together. Combining with network pharmacology and electrophysiological experiments, our study reveals the potential mechanisms of Arisaema cum Bile for the treatment of epilepsy in a "multi-ingredients, multi-targets and multi-pathways" manner. Our study provides a reference for further studies of Arisaema cum Bile.