Multi-omics integration reveals Yu-Xue-Bi tablets attenuate rheumatoid arthritis via metabolic reprogramming-mediated Piezo1 suppression (RNA-Seq)

As a systemic chronic inflammatory disease, Rheumatoid arthritis (RA) is characterized by progressive inflammation, 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 exhibits 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 metabonomic 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.

类风湿关节炎（Rheumatoid arthritis, RA）是一种系统性慢性炎症性疾病，以进行性炎症、骨与软骨破坏为特征，可导致显著残疾、寿命缩短及死亡率升高。临床常用的传统治疗药物包括非甾体抗炎药（nonsteroidal anti-inflammatory drugs, NSAIDs）、改善病情抗风湿药（disease-modifying antirheumatic drugs, DMARDs）及糖皮质激素，但此类药物均伴随显著不良反应。长期给药可诱发多种毒性反应，如肝毒性、肾毒性、骨质疏松症及感染易感性升高。尽管新型生物制剂的疗效有所提升，但可能增加严重感染与恶性肿瘤的发病风险。此外，尚有部分患者对这类生物治疗应答不佳。鉴于当前治疗手段存在诸多局限，开发更安全有效的类风湿关节炎治疗靶点与策略迫在眉睫。本研究报道了经典中药方剂玉血痹片（Yu-Xue-Bi Tablets, YXB）治疗类风湿关节炎的疗效。经玉血痹片干预的胶原诱导性关节炎（collagen-induced arthritis, CIA）模型小鼠整体健康状况得到改善，关节结构完整性与局部炎症状态均显著缓解。机制层面，滑膜组织的RNA测序（RNA-seq）分析显示，玉血痹片通过抑制机械敏感性离子通道Piezo1发挥类风湿关节炎治疗作用。整合代谢组学与转录组学分析结果表明，玉血痹片可改善胶原诱导性关节炎模型小鼠的代谢紊乱，进而下调Piezo1的表达，该结论在原代巨噬细胞中得到了验证。综上，本研究证实玉血痹片可通过代谢重编程抑制Piezo1的表达，从而缓解类风湿关节炎，为临床类风湿关节炎治疗提供了全新的策略。