Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China.
Institute of Bioinformatics and Medical Engineering School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001, China.
ChemMedChem. 2020 Mar 18;15(6):473-480. doi: 10.1002/cmdc.201900499. Epub 2019 Dec 20.
Actein is the main active ingredient of medicinal plant Cimicifuga racemosa (L.) Nutt, which has been reported to have various pharmacological effects, but the mechanism of actein remains undetermined. In this study, systems chemical biology methods were used to predict the targets and elucidate the pharmacological mechanisms of actein. First, 54 gene co-expression modules were obtained by biclustering. Then, the top 1 % agents with the highest regulatory similarity were screened out to be highly functionally similar to actein. Finally, the results of molecular docking and molecular dynamics simulation showed that actein has a stronger interaction with eight targets than original ligands. It suggests that the antipsychotic effect of actein probably occurs by targeting the key residues of the eight receptors, which are compatible with previously reported information. This study not only provides predicted targets of actein, but also a new method for exploring the mechanisms of other natural products in drug discovery.
升麻素有多种药理作用,其主要活性成分是升麻属药用植物升麻(Cimicifuga racemosa (L.) Nutt)中的阿替生。然而,其作用机制尚不清楚。本研究采用系统化学生物学方法预测阿替生的作用靶点,并阐明其药理作用机制。首先,通过双聚类获得了 54 个基因共表达模块。然后,筛选出调控相似度最高的前 1%的药物,这些药物与阿替生具有高度功能相似性。最后,分子对接和分子动力学模拟的结果表明,阿替生与 8 个靶标之间的相互作用比原配体更强。这表明阿替生的抗精神病作用可能是通过作用于这 8 个受体的关键残基来实现的,这与之前报道的信息一致。本研究不仅为阿替生提供了预测靶点,也为药物发现中探索其他天然产物的作用机制提供了新方法。