Tilianin attenuates inflammasome activation in endothelial progenitor cells to mitigate myocardial ischemia-reperfusion injury

• Published in: PloS one 2024-10, Vol.19 (10), p.e0311624
• Main Authors: Wang, Miaomiao, Li, Jiapeng, Hu, Xu, Fu, Mengmeng, Li, Xiaoxue, Damdinjave, Davaadagva, Xu, Ming, Zheng, Ruifang, Xing, Jianguo
• Format: Article
• Language: English
• Subjects: Activation analysis; Animals; Anti-inflammatory agents; Atherosclerosis; Biology and Life Sciences; Bone marrow; Cardiomyocytes; Cardiovascular disease; Cardiovascular diseases; Care and treatment; Cell activation; Cells (biology); Complex formation; Complications and side effects; Coronary vessels; Disease Models, Animal; Endothelial Progenitor Cells - drug effects; Endothelial Progenitor Cells - metabolism; Enzyme-linked immunosorbent assay; Flavonoids - pharmacology; Glycosides - pharmacology; Heart diseases; Hypoxia; Immunofluorescence; Inflammasomes; Inflammasomes - drug effects; Inflammasomes - metabolism; Inflammatory response; Injuries; Ischemia; Laboratory animals; Male; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Myocardial ischemia; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardium; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Oligomerization; Pharmacology; Progenitor cells; Protein structure; Proteins; Reperfusion; Reperfusion injury; Research and Analysis Methods; Trauma; Vascularization; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0311624

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.