Multiomics Integration Reveals Yu-Xue-Bi Tablets Attenuate Rheumatoid Arthritis via Metabolic Reprogramming-Mediated Piezo1 Suppression

As a systemic chronic inflammatory disease, Rheumatoid arthritis (RA) is characterized by progressive inflammation and bone and cartilage destruction, leading to significant disability, reduced lifespan, and increased mortality. The clinical use of conventional medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and corticosteroids, is associated with significant adverse effects. Long-term administration may induce various toxicities, such as hepatotoxicity, nephrotoxicity, osteoporosis, and heightened infection susceptibility. While newer biological agents demonstrate improved efficacy, they may elevate risks of serious infections and malignancies. Additionally, a subset of patients exhibit inadequate response to these biologic therapies. Given the limitations of current therapies, identifying safer and more effective therapeutic targets and strategies for RA is imperative. Here, we report the efficacy of Yu-Xue-Bi Tablets (YXB), a classic traditional Chinese medicine (TCM) formula, in treating RA. YXB-treated collagen-induced arthritis (CIA) mice exhibited improved general health with markedly ameliorated joint integrity and local inflammation. Mechanistically, RNA-seq analysis of synovial tissue revealed that YXB exerts therapeutic effects in RA by suppressing the mechanosensitive ion channel Piezo1. Integrated metabolomic and transcriptomic analyses suggested that YXB ameliorates metabolic disorders in CIA mice, leading to Piezo1 downregulation, a finding validated in primary macrophages. Collectively, our findings demonstrate that YXB alleviates RA by suppressing Piezo1 expression via metabolic reprogramming, offering a novel therapeutic strategy for the clinical treatment of RA.