Chronic kidney disease is a common disease closely related to renal tubular inflammation and oxidative stress, and no effective treatment is available. Activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important factor in renal inflammation, but the mechanism remains unclear. Micheliolide (MCL), which is derived from parthenolide, is a new compound with antioxidative and anti-inflammatory effects and has multiple roles in tumors and inflammatory diseases. In this study, we investigated the effect of MCL on lipopolysaccharide- (LPS-) induced inflammation in renal tubular cells and the related mechanism. We found that MCL significantly suppressed the LPS-induced NF-κB signaling and inflammatory expression of cytokines, such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in a rat renal proximal tubular cell line (NRK-52E). MCL also prevented LPS- and adenosine triphosphate-induced NLRP3 inflammasome activation in vitro, as evidenced by the inhibition of NLRP3 expression, caspase-1 cleavage, and interleukin-1β and interleukin-18 maturation and secretion. Additionally, MCL inhibited the reduction of mitochondrial membrane potential and decreases the release of reactive oxygen species (ROS). Moreover, MCL can prevent NLRP3 inflammasome activation induced by rotenone, a well-known mitochondrial ROS (mROS) agonist, indicating that the mechanism of MCL’s anti-inflammatory effect may be closely related to the mROS. In conclusion, our study indicates that MCL can inhibit LPS-induced renal inflammation through suppressing the mROS/NF-κB/NLRP3 axis in tubular epithelial cells.

中文翻译：

---

Micheliolide 通过调节肾小管上皮细胞中的 mROS/NF-κB/NLRP3 轴减轻脂多糖诱导的炎症。

慢性肾脏病是一种与肾小管炎症和氧化应激密切相关的常见疾病，目前尚无有效的治疗方法。核苷酸结合寡聚化结构域样受体蛋白 3 (NLRP3) 炎症小体的激活是肾脏炎症的重要因素，但其机制尚不清楚。Micheliolide (MCL) 来源于小白菊内酯，是一种具有抗氧化和抗炎作用的新型化合物，在肿瘤和炎症性疾病中具有多重作用。在这项研究中，我们研究了 MCL 对脂多糖 (LPS) 诱导的肾小管细胞炎症的影响及其相关机制。我们发现，MCL显著抑制LPS诱导的NF- κ乙信令和细胞因子的炎症表达，如肿瘤坏死因子大鼠肾近端肾小管细胞系 (NRK-52E) 中的α和单核细胞趋化蛋白-1。MCL 还在体外阻止了 LPS 和三磷酸腺苷诱导的 NLRP3 炎性体激活，这可以通过抑制 NLRP3 表达、caspase-1 切割和白细胞介素 1 β来证明和白细胞介素 18 的成熟和分泌。此外，MCL 抑制线粒体膜电位的降低并减少活性氧 (ROS) 的释放。此外，MCL可以阻止鱼藤酮（一种众所周知的线粒体ROS（mROS）激动剂）诱导的NLRP3炎性体激活，表明MCL抗炎作用的机制可能与mROS密切相关。总之，我们的研究表明，MCL可以抑制LPS诱导的肾脏炎症通过抑制活性氧代谢/ NF- κ在肾小管上皮细胞B / NLRP3轴线。