Coix Seed Oil Ameliorates Rheumatoid Arthritis by Modulating Inflammation-Associated Metabolic Pathways

Rheumatoid arthritis (RA) is a chronic disease that primarily manifests as symmetrical joint inflammation. Although Coix Seed Oil (CSO) has demonstrated anti-inflammatory effects in RA rat models, its systemic metabolic regulatory mechanisms remain unclear. Therefore, we aimed to investigate whether CSO ameliorates RA by modulating inflammation-associated metabolic pathways. Ultra-High-Performance Liquid Chromatography (UHPLC)-Q Exactive HF-X-MS-based metabolomics was used to profile metabolites in the synovial tissue and serum of complete Freund's adjuvant (CFA)-induced RA rats. Systematically altered metabolites and their associated pathways were identified using multivariate analysis and pattern recognition. CSO treatment modulated 16 RA-related biomarkers in rat synovial tissues and 12 in the serum, which mainly affected amino acids, arachidonic acids, lipids, sphingolipids, and carnitines. These metabolites were associated with eight perturbed metabolic pathways that were predominantly involved in inflammatory responses. This study demonstrated that CSO has significant anti-RA effects on pharmacodynamic activity and metabolic network regulation. Additionally, inflammation-associated metabolic pathways are closely linked to the therapeutic efficacy of CSO in RA treatment.