Objective: Epilepsy is a neuronal disorder that is characterized by epileptic seizures and linked with abnormal neural functioning in the brain. Traditional Chinese medicine (TCM) formula Chaibei Zhixian decoction (CZD) has been widely used for epilepsy in China while the pharmacological mechanisms are still unclear. In the present study, systematic and comprehensive network pharmacology was utilized for the first time to reveal the potential pharmacological mechanisms of CZD on epilepsy.
Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform was utilized for the development of an ingredients-targets database. After identifying epileptic targets of CZD, their interaction with other proteins was estimated based on protein-protein interaction network created from STITCH and gene ontology (GO) enrichment analysis utilizing Cytoscape-ClueGO plugin.
Results: CZD formula was found to have 643 chemical ingredients, and the potential protein targets of these ingredients were 5230, as retrieved from TCMSP database. Twenty-six protein targets were found to be associated with epilepsy. Thirteen hub genes were regulated by CZD in epilepsy, including estradiol, ESR1, ESR2, SRC, CTNNB1, EP300, MAPK1, MAPK3, SP1, BRCA1, NCOA3, CHRM1, and GSK3B. The results of GO terms analysis showed that 8 GO terms were recovered in the form of 3 clusters, including negative regulation of protein kinase B signaling, positive regulation of interleukin-1 production, and microvillus assembly.
Conclusions: Network pharmacology approach provides better understanding of the underlying pharmacological mechanisms of CZD on epilepsy. Estradiol, ESR1, ESR2, CTNNB1, EP300, MAPK1, MAPK3, BRCA1, and GSK3B are likely to be important molecules regulated by CZD in treatment of epilepsy. Negative regulation of protein kinase B signaling may play vital roles in the treatment of epilepsy by CZD.