Molecular insights into the anti-inflammatory and antifibrotic effects of licorice-ginger decoction in experimental models of inflammatory arthritis-associated lung fibrosis.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe autoimmune complication lacking effective treatments. This study investigates the molecular mechanisms underlying the therapeutic effects of licorice-ginger decoction (GGD) in experimental models relevant to arthritis-associated lung fibrosis. Utilizing network pharmacology, transcriptomic sequencing, and molecular docking analyses, we identified the STAT1/ICAM1/IL-17A signaling pathway as crucial for GGD efficacy. Experimental validation in both cellular and murine models demonstrated that GGD markedly alleviated body weight loss, reduced arthritis severity, and improved pulmonary pathological injury under inflammatory arthritis conditions. Mechanistic analyses revealed direct binding of Kae and QR to STAT1/ICAM1, leading to IL-17A inhibition and mitigation of epithelial-mesenchymal transition (EMT) and fibroblast activation. Notably, overexpression of STAT1 attenuated the therapeutic effects of GGD. This study provides mechanistic insights into the anti-inflammatory and antifibrotic effects of GGD in experimental models relevant to arthritis-associated lung fibrosis and offers a potential framework for future mechanistic studies and translational research of classical Chinese formulations.