Investigation on the active ingredient and mechanism of Cannabis sativa L. for treating epilepsy based on network pharmacology

Abstract

Cannabis sativa L. (cannabis) is a medicinal plant and has been used for many years for the treatment of epilepsy (EP), which is a common neurological disease. This study aimed to investigate the mechanism of cannabis action in EP, with emphasis on the leading compounds, targets and pathways. In this study, systematic pharmacology and bioinformatics approaches were employed to identify the active ingredients and potential targets of cannabis for treating EP. Furthermore, network construction, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and molecular docking were used to elucidate the mechanism of cannabis against EP. A total of 360 compounds were collected in this work. Among them, 226 active compounds and 116 predicted targets were obtained based on absorption, distribution, metabolism and excretion (ADME) screening and databases, respectively. Among the 226 active compounds, most were cannabinoids. The topological analysis showed that cannabinoid receptor 1, albumin and glycogen synthase kinase-3 beta (CNR1, ALB and GSK3B) were the key targets with intense interaction. The GO and KEGG enrichment analysis suggested cannabis might produce the antiepileptic effects by regulating many pathways, including calcium signalling pathway, MAPK signalling pathway, GABAergic synapse, etc. Additionally, cannabinol methyl ether (M54) might be the leading compound based on molecular docking. Consequently, this study holistically illuminates the active constituents and mechanism of cannabis based on network pharmacology, which contributes to searching for leading compounds and development of new drugs in the treatment of EP. Supplemental data for this article is available online at https://doi.org/10.1080/13102818.2021.1942208 .