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 .

摘要

大麻L.（大麻）是一种药用植物，多年来一直用于治疗癫痫（EP），这是一种常见的神经系统疾病。本研究旨在研究大麻在 EP 中的作用机制，重点是主要化合物、靶点和途径。在这项研究中，采用系统药理学和生物信息学方法来确定大麻治疗 EP 的活性成分和潜在靶点。此外，网络构建、基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析和分子对接被用来阐明大麻对抗EP的机制。本研究共收集到 360 种化合物。其中，根据吸收、分布、代谢和排泄 (ADME) 筛选和数据库，分别。在 226 种活性化合物中，大多数是大麻素。拓扑分析表明，大麻素受体 1、白蛋白和糖原合酶激酶 3 β（CNR1、ALB 和 GSK3B）是具有强烈相互作用的关键目标。GO和KEGG富集分析表明，大麻可能通过调节钙信号通路、MAPK信号通路、GABA能突触等多种途径产生抗癫痫作用。此外，大麻酚甲基醚（M54）可能是基于分子对接的领先化合物。因此，本研究基于网络药理学全面阐明了大麻的活性成分和作用机制，有助于寻找治疗EP的先导化合物和新药的开发。

本文的补充数据可在 https://doi.org/10.1080/13102818.2021.1942208 在线获得。