The classic NLRP3 inflammasome and NF-κB molecular pathways are activated in many inflammatory-related diseases, such as pleurisy. Because oridonin (Ori) has been indicated as a covalent NLRP3 inhibitor with strong anti-inflammasome activity, we herein aimed to assess the effects of Ori in a mouse model of carrageenan (CAR)-induced pleurisy. The results showed that CAR caused hemorrhaging and exudation of lung tissues and the release of inflammatory factors (TNF-α, IL-6 and IL-1β), effects that were significantly reduced by treatment with Ori. In addition, increased neutrophil infiltration, protein concentrations and volumes were found in the exudates of the CAR group, and these phenomena were suppressed by Ori treatment. Regarding cellular pathways, Ori could alleviate the CAR-activated NF-κB and TXNIP/NLRP3 pathways. Additionally, oxidative stress was shown to be involved in the pathogenesis of pleurisy, but possible mechanisms remain to be explored. Herein, Ori reversed the CAR-induced depletion of GSH and SOD and the CAR-induced increases in ROS, MPO and MDA levels. Furthermore, Ori inhibited NOX-4 levels, initiated the dissociation of KEAP-1 from Nrf2, activated the downstream genes HO-1 and exerted antioxidative effects on CAR-induced pleurisy. In conclusion, Ori conferred protection against CAR-induced pleurisy via Nrf2-dependent antioxidative and NLRP3-dependent anti-inflammatory properties.

中文翻译：

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冬凌草甲素通过激活KEAP-1 / Nrf2途径和抑制TXNIP / NLRP3和NF-κB途径来减轻角叉菜胶引起的胸膜炎。

经典的NLRP3炎性体和NF-κB分子途径在许多与炎症相关的疾病（如胸膜炎）中被激活。因为Oridonin（Ori）已被指示为具有强大的抗炎小体活性的共价NLRP3抑制剂，我们在此旨在评估Ori在角叉菜胶（CAR）诱导的胸膜炎小鼠模型中的作用。结果表明，CAR引起肺组织的出血和渗出以及炎性因子（TNF-α，IL-6和IL-1β）的释放，而Ori治疗可显着降低其影响。此外，在CAR组的渗出液中发现中性粒细胞浸润，蛋白质浓度和体积增加，并且这些现象通过Ori治疗得到抑制。关于细胞途径，Ori可以减轻CAR激活的NF-κB和TXNIP / NLRP3途径。另外，氧化应激被证明与胸膜炎的发病机制有关，但可能的机制尚待探索。在本文中，Ori逆转了CAR诱导的GSH和SOD耗竭以及CAR诱导的ROS，MPO和MDA水平升高。此外，Ori抑制NOX-4水平，启动KEAP-1与Nrf2的解离，激活下游基因HO-1，并对CAR引起的胸膜炎发挥抗氧化作用。总之，Ori通过Nrf2依赖的抗氧化和NLRP3依赖的抗炎特性赋予了针对CAR引起的胸膜炎的保护。引发了KEAP-1与Nrf2的分离，激活了下游基因HO-1，并对CAR引起的胸膜炎发挥了抗氧化作用。总之，Ori通过依赖Nrf2的抗氧化和依赖NLRP3的抗炎特性赋予针对CAR引起的胸膜炎的保护作用。引发了KEAP-1与Nrf2的分离，激活了下游基因HO-1，并对CAR引起的胸膜炎发挥了抗氧化作用。总之，Ori通过依赖Nrf2的抗氧化和依赖NLRP3的抗炎特性赋予了针对CAR引起的胸膜炎的保护作用。