Ruscogenin alleviates palmitic acid-induced endothelial cell inflammation by suppressing TXNIP/NLRP3 pathway

Purpose: To investigate the involvement of ruscogenin in palmitic acid (PA)-induced endothelial cell inflammation. Method: Cultured human umbilical vein endothelial cells (HUVECs) were divided into five groups: control (normal untreated cells), PA (cell treated with palmitic acid), and PA + ruscogenin (1, 10, or 30 mu M). Cell viability and apoptosis rate were determined using MTT (3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazolium bromide) and flow cytometty assays, respectively. The levels of cytokines, including interleukin-1 beta (IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemo-attractant protein-1 (MCP-1) were determined by an enzyme-linked immunosorbent assay. Western blotting and real-time polymerase chain reaction (RT-PCR) were used to evaluate the underlying mechanisms of action. Results: PA treatment decreased the viability of HUVECs and induced apoptosis (p < 0.05). Ruscogenin attenuated PA-induced cell death in a dose-dependent manner (p < 0.05). On the other hand, PA induced an increase in IL-1 beta, TNF-alpha, ICAM-1, MCP-1, TXNIP (thioredoxin-interacting protein), as well as NLRP3 (nucleotide oligomerization domain-, leucine-rich repeat- and pyrin domain-containing protein 3), all of which were attenuated by ruscogenin (p < 0.05). Conclusion: Ruscogenin alleviates PA-induced endothelial cell inflammation via TXNIP/NLRP3 pathway, thereby providing an insight into new therapeutic strategies to treat cardiovascular diseases.