Molecular mechanism of quercetin in treating RA-ILD based on network pharmacology, molecular docking, and experimental validation.

Rheumatoid arthritis (RA) is an autoimmune disease that is associated with systemic complications. Interstitial lung disease (ILD) is the most common pulmonary complication and second leading cause of death in patients with RA. In this study, we used network pharmacology and experimental validation to identify the targets and pathways of quercetin (Que) in the treatment of RA-associated ILD (RA-ILD). A total of 32 potential targets of Que for RA-ILD treatment were screened from six databases, and 10 core targets were screened using protein-protein interaction network analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and molecular docking were employed to explore the potential mechanisms of Que in RA-ILD treatment. The results suggested the IL-17 signaling pathway as an important pathway through which Que alleviates RA-ILD. Subsequently, LPS (1 µg/ml) was used to establish an inflammation model on RAW 264.7 cells, and different concentrations of Que (25, 50, and 100 µM) were used for intervention. Que significantly reduced the expression levels of IL-17, TNF-α, IL-6, and IL-1β in RAW 264.7 cells. Our findings suggest that Que alleviates RA-ILD by regulating the IL-17 signaling pathway and reducing inflammation.