Mechanism of Dark Plum In Treatment of Sjögren's Syndrome Based On Network Pharmacology And Molecular Docking​

Abstract

Background: Modern medicine has no cure for the xerostomia caused by the early onset of Sjögren's syndrome (SS).Dark plum is a common Chinese herbal medicine used to relieve xerostomia. However, the molecular mechanisms of the effects of dark plum are unknown. In this study, network pharmacology and molecular docking were used to investigate the mechanisms of action of dark plum on SS.Materials and method: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database was used to identify the active components and targets of dark plum, and the UniProt database was used to identify the genes encoding these targets. SS-related targets were also identified from the GeneCards and OMIM databases. By finding the intersection of the targets of the compounds and the targets of SS, the predicted targets of dark plum in the treatment of SS were obtained. Further investigation of the active compounds and their targets was carried out by constructing a network of "medicine-candidate compound-target-disease" using Cytoscape 3.7.2, the Protein-Protein Interaction(PPI) network using the STRING database and Cytoscape 3.7.2, and key targets were identified by Gene Ontology( GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on R software. Finally, molecular docking was used to verify the affinity of the candidate compounds to the key targets.Results: Quercetin, beta-sitosterol, and kaempferol in dark plum interact with AKT1, IL-6, IL-1B, JUN, CASP3, and MAPK8. These results suggest that dark plum exerts its therapeutic effects on the peripheral gland injury of SS and its secondary cardiovascular disease and tumorigenesis through anti-inflammatory, anti-oxidant, and anti-tumor pathways.Conclusion: With network pharmacology, this study systematically identified the main active components, targets, and specific mechanisms of the therapeutic effects of dark plum on SS, providing both a theoretical basis and research direction for further investigations on dark plum.