Isoliquiritin ameliorates rheumatoid arthritis by inhibiting S1P synthesis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation and pain, often leading to joint deformity and functional impairment. By comparing serum metabolic profiles between 50 pairs of RA patients and healthy controls, we identified aberrant expression of sphingosine-1-phosphate (S1P) in RA patient serum, which was closely associated with inflammatory and autoimmune responses. Through integrated bioinformatic analysis and in vitro/in vivo experiments, we demonstrated that isoliquiritin (ISL) binds to protein kinase C (PRKC), thereby inhibiting the activation of sphingosine kinase 1 (SphK1), reducing S1P production, suppressing abnormal proliferation of fibroblast-like synoviocytes (FLS), and ultimately alleviating RA symptoms.