Identifying potential therapeutic targets of a natural product Jujuboside B for insomnia through network pharmacology

Abstract

Knowledge of the interactome improves the understanding of disease metabolism. Biological information about interactions among genes and their protein products, computationally extracted in the context of SysBiomics, can hint at molecular causes of diseases, be essential for understanding biological systems, and provide clues for new therapeutic approaches. Quick and efficient access to this data have become critical issues for biologists. We have implemented a computational platform that integrates pathway, protein-protein interaction, differentially expressed genome and literature mining data to result in comprehensive networks for insomnia and intervention effects of Jujuboside B (JuB). The interaction data were imported into Cytoscape software, a popular bioinformatics package for biological network visualization and data integration, for screening the central nodes of the network, exploiting functional study of the central node genes, exploring the mechanism of insomnia. Results showed that seven differentially expressed genes confirmed by Cytoscape as the central nodes of the network in insomnia had interactions, forming a complicated interaction network (77 nodes, 96 edges). Among gene nodes, HBA1, LEP, MAOA, PRNP, GHRL, CLOCK and SLC6A4 were verified as the genes with maximal differential expressions. Of note, we further observed that the HBA1, LEP, SLC6A4 and MAOA were JuB target genes. The interaction network of the differentially expressed genes, especially the central nodes of this network, can provide clues to the insomnia, early diagnosis and molecular targeted therapy. Our findings demonstrate that the integration of interaction network in genomic space can not only speed the genome-wide identification of drug targets but also find new applications for the existing drugs.

Comparative pharmacokinetics of six major compounds in normal and insomnia rats after oral administration of Ziziphi Spinosae Semen aqueous extract

“…Spinosin has also been reported to potentiate pentobarbital-induced sleep via a serotonergic mechanism while 6 ‴ -feruloylspinosin has been proven to induce the prolongation of hexobarbital sleeping time in mice [ 9 , 10 ]. JuA and JuB are the major saponins, and both exhibit the hypnotic effect by adjusting the mRNA expression of GABA receptor subunit and partially regulating the amino-acid metabolism pathway [ [11] , [12] , [13] ]. Recent studies indicate that magnoflorine has sedative and anxiolytic effects, and coclaurine causes sedative bioactivity by interacting with melatonin receptors [ 6 , 14 ].…”

Retracted Article: A high-throughput metabolomics strategy for discovering the influence of differential metabolites and metabolic pathways of huaxian capsules on sepsis-associated Qi deficiency and blood stasis syndrome

“…12 It can monitor and quantify the changes in small molecule metabolites, such as fatty acids, amino acids, peptides, nucleic acids, organic acids, vitamins, and carbohydrates, in an organism or a biological sample during the ultimate response to the endogenous and exogenous factors. 13 Metabolomics can systematically and holistically probe the metabolome and metabolic pathway variations to explore the efficacy of a therapy, particularly that of TCM, which is difficult to study using conventional pharmacological methods due to its multi-component and multi-target peculiarity. 14 Currently, metabolomics has been successfully applied to detect metabolic changes in sepsis and characterize biochemical pathways.…”

Rapid lipidomics analysis for sepsis-induced liver injury in rats and insights into lipid metabolic pathways using ultra-performance liquid chromatography/mass spectrometry

“…Compared with the control group, PE(20:4 (8Z,11Z,14Z,17Z)/15:0) was lower and PE(14:1(9Z)/24:1(15Z)) was increased in the model group, indicating that abnormal material identication and transport occurred in the cell, which has been shown to cause metabolic disorders. 23 Some studies have shown that for cholesterol to function properly in the body and to show proper metabolism, it must be combined with linoleic acid. Body lipid metabolism disorders caused by insufficient amounts of linoleic acid have been shown to result in reduced immunity, forgetfulness, fatigue, vision loss and other symptoms.…”