Abstract
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.
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The datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request.
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This study was supported by the National Natural Science Foundation of China (82074358) and the Postgraduate Research and Practice Innovation Program of Jiangsu Province (KYCX22_1947).
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Jing Wang and Zhichao Wang conceptualization, conceptualized and designed the project, performed the experiments, and wrote the manuscript. Yang Zhao and Le Bai provided technical support. Yun Wei and Tongxing Huang revised revisions of the manuscript. Xianmei Zhou and Yong Xu supervised the study. The authors declare that all data were generated in-house and that no paper mill was used.
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Wang, J., Wang, Z., Zhao, Y. et al. Molecular mechanism of quercetin in treating RA-ILD based on network pharmacology, molecular docking, and experimental validation. Naunyn-Schmiedeberg's Arch Pharmacol 397, 3077–3092 (2024). https://doi.org/10.1007/s00210-023-02772-3
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DOI: https://doi.org/10.1007/s00210-023-02772-3