DataSheet_1_Erianin: A Direct NLRP3 Inhibitor With Remarkable Anti-Inflammatory Activity.docx

Erianin (Eri) is the extract of Dendrobium chrysotoxum Lindl. The NLRP3 inflammasome is a multiprotein complex that plays key roles in a wide variety of chronic inflammation-driven human diseases. Nevertheless, little is known about the protection of Eri against NLRP3 inflammasome-related diseases. In this study, we demonstrated that Eri inhibited NLRP3 inflammasome activation in vitro and in vivo. Mechanistically, Eri directly interacted with NLRP3, leading to inhibition of NLRP3 inflammasome assembly. Eri associated with the Walker A motif in the NACHT domain and suppressed NLRP3 ATPase activity. In mouse models, Eri had therapeutic effects on peritonitis, gouty arthritis and type 2 diabetes, via NLRP3. More importantly, Eri was active ex vivo for synovial fluid cells and monocytes from patients with IAV infection and gout. Eri may serve as a potential novel therapeutic compound against NLRP3-driven diseases.

Erianin（Eri）为兰科植物Dendrobium chrysotoxum Lindl.的提取物。NLRP3炎症小体是一种多功能蛋白复合体，在多种由慢性炎症驱动的人类疾病中扮演关键角色。然而，关于Eri对NLRP3炎症小体相关疾病的保护作用知之甚少。在本研究中，我们证实了Eri能够在体外和体内抑制NLRP3炎症小体的激活。从机制上讲，Eri直接与NLRP3相互作用，导致NLRP3炎症小体组装的抑制。Eri与NACHT结构域中的Walker A基序相结合，并抑制NLRP3的ATP酶活性。在小鼠模型中，Eri通过NLRP3途径对腹膜炎、痛风性关节炎和2型糖尿病具有治疗效果。更重要的是，Eri在体外对IAV感染和痛风患者的滑液细胞和单核细胞具有活性。Eri可能成为针对NLRP3驱动疾病的一种潜在的新型治疗化合物。