PDF(Pubmed)
Abstract：
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.
摘要：
类风湿性关节炎(RA)是一种以关节炎症改变为特征的慢性自身免疫性疾病,其病因尚不清楚。现在已经确定调节细胞死亡(RCD)和中性粒细胞的迁移在RA的发病机制中起重要作用。雷公藤。f(TwHF)是从雷公藤根提取的总皂苷。f,卫斯理科的一种植物，具有较强的抗炎和免疫调节作用,已被用作临床治疗RA的基础药物。尽管TwHF治疗效果良好,TwHF的作用机制尚不清楚。一些研究表明，雷公藤多甙类药物，其中TwHF是主要成分，在RA的临床治疗中取得了优异的疗效。调查还发现，TwHF可以影响细胞RCD，细胞迁移，细胞增殖，以及凋亡相关的Hippo信号通路。在这项研究中,我们首先通过网络药理学和转录组分析分析了RA患者的RCD和中性粒细胞的迁移差异.随后，我们用了电子显微镜,免疫荧光，等方法鉴定中性粒细胞的RCD表型。在胶原诱导性关节炎（CIA）模型中，我们证明了雷公藤甲素（TwHF的主要活性成分）可以通过减少骨破坏和中性粒细胞浸润来减轻关节炎的进展。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陷阱（NET）的形成，并以Hippo途径依赖性方式阻碍了中性粒细胞的迁移过程。一起来看,提示雷公藤甲素具有治疗RA的潜力,为TwHF的临床应用提供了理论支持,作为中药，在RA。
