Key Laboratory of Xinjiang Phytomedicine Resources for Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, China.
Xinjiang Institute of Materia Medica, Xinjiang Key Laboratory of Uygur Medicine, Urumqi, China.
PLoS One. 2024 Oct 10;19(10):e0311624. doi: 10.1371/journal.pone.0311624. eCollection 2024.
Tilianin (TIL), a bioactive component derived from Dracocephalum Moldavica L., has been recognized for its anti-inflammatory properties. However, its effects on the Nlrp3 inflammasome within endothelial progenitor cells (EPCs) during myocardial ischemia-reperfusion injury (MIRI) remain unexplored. This study aimed to elucidate the role of TIL in modulating Nlrp3 inflammasome activation under MIRI conditions. A mouse model of MIRI was established to assess the therapeutic potential of TIL. EPCs treated with TIL at concentrations of 5, 10, and 20 μM were administered into the myocardium before reperfusion. Additionally, the cardioprotective effects of TIL were further examined by pre-treating EPCs with the compound before exposing them to hypoxia/reoxygenation (H/R) using cardiomyocyte supernatants. The impact on Nlrp3 inflammasome was assessed through western blotting, immunofluorescence, and ELISA. Our results showed that TIL concentration-dependently inhibited Nlrp3 inflammasome-related protein levels,and inhibited Asc oligomerization and Asc-Speck complex formation in EPCs, resulting in improved the migratory capacity and vascular structure formation of EPCs. In addition, TIL-treated EPCs significantly attenuated I/R injury and improved cardiac function. These results suggest that TIL ameliorates the inflammatory response in EPCs by suppressing Nlrp3 inflammasome activation, thereby facilitating neovascularization in the myocardium and conferring protection against MIRI. The study provides valuable insights into the potential of TIL as a therapeutic agent for cardiovascular diseases linked to ischemia-reperfusion injury.
延龄草素（TIL）是一种来源于Dracocephalum Moldavica L. 的生物活性成分，具有抗炎作用。然而，其在心肌缺血再灌注损伤（MIRI）期间对内皮祖细胞（EPC）中Nlrp3 炎性小体的影响尚不清楚。本研究旨在阐明 TIL 在调节 MIRI 条件下 Nlrp3 炎性小体激活中的作用。建立 MIRI 小鼠模型评估 TIL 的治疗潜力。将浓度为 5、10 和 20 μM 的 TIL 处理的 EPC 在心梗前注入心肌再灌注。此外，通过用细胞培养液上清液进行缺氧/复氧（H/R）预处理 EPC，进一步研究 TIL 的心脏保护作用。通过 Western blot、免疫荧光和 ELISA 评估对 Nlrp3 炎性小体的影响。结果显示，TIL 呈浓度依赖性抑制 Nlrp3 炎性小体相关蛋白水平，并抑制 EPC 中 Asc 寡聚体和 Asc-Speck 复合物形成，从而改善 EPC 的迁移能力和血管结构形成。此外，TIL 处理的 EPC 显著减轻 I/R 损伤并改善心功能。这些结果表明，TIL 通过抑制 Nlrp3 炎性小体激活改善 EPC 中的炎症反应，从而促进心肌中的新生血管形成并对 MIRI 提供保护。该研究为 TIL 作为与缺血再灌注损伤相关的心血管疾病的治疗剂提供了有价值的见解。
