Network pharmacology-based strategy to investigate the mechanisms of artemisinin in treating primary Sjögren's syndrome

Objective: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation.

Methods: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms.

Results: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, Apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model.

Conclusion: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.

Artemisinin; Network pharmacology; Regulatory T cells; Sjögren’s syndrome; Th17 cells.