Deciphering the latent mechanism of nobiletin in the treatment of metabolic syndrome based on network pharmacology and molecular docking

doi:10.5246/jcps.2022.11.069

Abstract

Abstract:

Nobiletin (NOB) may have a potential effect on metabolic syndrome. In the present study, we aimed to explore the latent mechanisms of NOB for the treatment of metabolic syndrome based on network pharmacology and molecular docking methods. The potential targets of NOB were retrieved and identified from six databases, such as the Traditional Chinese Medicine Systems Pharmacology Database. The metabolic syndrome-related targets were retrieved from six databases as follows: the DrugBank database, GeneCards database, the Online Mendelian Inheritance in Man database, PharmGKB database, Therapeutic Target Database, and DisGeNet database. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of 60 intersected genes were performed in R software (Bioconductor, clusterProfiler) to investigate the molecular mechanisms. Subsequently, the ingredient-target-pathway network of NOB was constructed and visualized through Cytoscape 3.8.0 software. Protein-protein interaction network was constructed to screen hub genes in the treatment of NOB on metabolic syndrome through The Search Tool for the Retrieval of Interacting Genes/Proteins and visualized by Cytoscape 3.8.0 software. Afterward, molecular docking was used to analyze the score of the hub genes with NOB. Cumulatively, 105 targets of NOB were identified. Moreover, 1975 metabolic syndrome-related genes were acquired from six databases after combining and deleting the repeated items, and the overlap of metabolic syndrome-related genes with NOB-related target genes identified 60 intersection genes of NOB against metabolic syndrome. Moreover, 1858 GO entries of NOB on metabolic syndrome were identified, and 153 pathways were screened based on GO and KEGG analyses. The target hub genes of NOB in MetS treatment were TP53, MAPK8, AKT1, GSK3B, HSP90AA1, CTNNB1, JUN, AR, ESR1, CCND1, HRAS, TNF, and PPARA. It was confirmed that lipid and atherosclerosis, together with the AGE-RAGE signaling pathway in diabetic complications, were putatively critical pathways of NOB in the treatment of metabolic syndrome. The molecular docking results revealed that most of 13 hub genes had a strong binding to NOB. Due to the versatile actions of NOB, it had the potential action on metabolic syndrome by multiple targets and multiple pathways.

Key words: Nobiletin, Metabolic syndrome, Network pharmacology, Molecular docking

Supporting:

Xiaohui Du, Hongyan Yang, Tao Wang, Hongxia Cui, Yu Lin, Hongling Li. Deciphering the latent mechanism of nobiletin in the treatment of metabolic syndrome based on network pharmacology and molecular docking[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(11): 803-823.

Figures/Tables 11

Table 1. Details of target genes of NOB.

Table 2. The topological parameters of target hub genes.

Table 3. Molecular docking results.

References 76

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