Research on the Potential Mechanism of Gypenosides on Treating Thyroid-Associated Ophthalmopathy Based on Network Pharmacology.

ABSTRACT

Thyroid-associated ophthalmopathy is the commonest orbital disease in adults. However, shortcomings still exist in treatments. The aim of this study was to identify the efficacy and potential mechanism of gypenosides in the treatment of thyroid-associated ophthalmopathy. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was screened for active compounds of gypenosides, and targets were predicted using Swiss Target Prediction. The targets of thyroid-associated ophthalmopathy were obtained from Online Mendelian Inheritance in Man, Comparative Toxicogenomic Database and GeneCards Human gene database. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome Pathways were determined based on the common targets. Protein-protein interaction (PPI) network was constructed to further understand of relationship among target genes, compounds and proteins. Molecular docking was performed to investigate the binding ability between gypenosides and hub genes. A total of 70 targets for gypenosides and 804 targets for thyroid-associated ophthalmopathy were obtained with 8 common targets identified. GO analysis and KEGG pathway analysis revealed that the hub genes were enriched in JAK-STAT, while Reactome pathways analysis indicated genes enriched in interleukin pathways. PPI network showed STAT1, STAT3, and STAT4 were at the center. Additionally, molecular docking indicated that STAT1 and STAT3 display good binding forces with gypenosides. This study indicates that target genes mainly enriched in JAK-STAT signaling pathway, particularly in STATs, which can be combined with gypenosides. This may suggest that gypenosides have curative effect on thyroid-associated ophthalmopathy via the JAK-STAT pathway.