Liu Pengyuan, Liu Huiyang, Sang Yali, Zhu Lingyan, Zhang Peiyao, Pang Chunyan, Wang Yongfu, Bai Li
Baotou Medical College, Inner Mongolia University of Science and Technology. Baotou 014000,China.
Department of Rheumatology and Immunology, the First Affiliated Hospital of Baotou Medical College, Baotou 014010, China.
J Transl Autoimmun. 2024 May 3;8:100242. doi: 10.1016/j.jtauto.2024.100242. eCollection 2024 Jun.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory changes in the joints, the etiology of which is unclear. It is now well established that regulated cell death (RCD) and migration of neutrophils play an important role in the pathogenesis of RA. Tripterygium wilfordii Hook.f (TwHF) is a total saponin extracted from the root of Tripterygium wilfordii Hook.f, a plant of the family Wesleyanaceae, which has strong anti-inflammatory and immunomodulatory effects and has been used as a basic drug in the clinical treatment of RA. Despite the good efficacy of TwHF treatment, the mechanism of action of TwHF remains unclear. Several studies have demonstrated that the drug tripterygium glycosides, in which TwHF is the main ingredient, has achieved excellent efficacy in the clinical treatment of RA. Investigations have also found that TwHF can affect cellular RCD, cell migration, cell proliferation, and the apoptosis-related Hippo signaling pathway. In this study, we first analyzed the RCD and migration differences of neutrophils in patients with RA through network pharmacology and transcriptome analysis. Subsequently, we used electron microscopy, immunofluorescence, and other methods to identify the RCD phenotype of neutrophils. In collagen-induced arthritis (CIA) model, we demonstrated that Triptolide (the main active ingredient in TwHF) could alleviate the progression of arthritis by reducing the bone destruction and the infiltration of neutrophils. Furthermore, in vitro experiments showed that Triptolide induced neutrophil apoptosis, inhibited the formation of neutrophil extracellular traps (NETs), and impeded the neutrophil migration process in a Hippo pathway-dependent manner. Taken together, these findings indicate that Triptolide has potential for treating RA and provide theoretical support for the clinical application of TwHF, as a traditional Chinese medicine, in RA.
类风湿关节炎（RA）是一种慢性自身免疫性疾病，其特征为关节的炎症性改变，病因尚不清楚。目前已明确，调节性细胞死亡（RCD）和中性粒细胞迁移在RA的发病机制中起重要作用。雷公藤多苷（TwHF）是从卫矛科植物雷公藤根中提取的总皂苷，具有较强的抗炎和免疫调节作用，已被用作RA临床治疗的基础药物。尽管TwHF治疗效果良好，但其作用机制仍不清楚。多项研究表明，以TwHF为主要成分的雷公藤总苷在RA临床治疗中取得了良好疗效。研究还发现，TwHF可影响细胞RCD、细胞迁移、细胞增殖以及与凋亡相关的Hippo信号通路。在本研究中，我们首先通过网络药理学和转录组分析，分析了RA患者中性粒细胞的RCD和迁移差异。随后，我们采用电子显微镜、免疫荧光等方法鉴定中性粒细胞的RCD表型。在胶原诱导的关节炎（CIA）模型中，我们证明了雷公藤甲素（TwHF中的主要活性成分）可通过减少骨破坏和中性粒细胞浸润来缓解关节炎的进展。此外，体外实验表明，雷公藤甲素诱导中性粒细胞凋亡，抑制中性粒细胞胞外诱捕网（NETs）的形成，并以Hippo通路依赖的方式阻碍中性粒细胞迁移过程。综上所述，这些发现表明雷公藤甲素具有治疗RA的潜力，并为TwHF作为中药在RA中的临床应用提供了理论支持。
