Abstract
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 μM). Cell viability and apoptosis rate were determined using MTT (3-(4,5)-dimethylthiahiazo(-z-y1)-3,5- di-phenytetrazolium bromide) and flow cytometry assays, respectively. The levels of cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), 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-1β, TNF-α, 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.
 Keywords: Ruscogenin, Palmitic acid, Endothelial cells, Inflammation, TXNIP, NLRP3, Cardiovascular diseases
Highlights
Cardiovascular diseases are the leading cause of death worldwide and involve abnormal endothelial cell inflammation [1]
Ruscogenin dose-dependently decreased the levels of IL-1β, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemo-attractant protein-1 (MCP-1)
These results suggest that ruscogenin effectively alleviated palmitic acid (PA)-induced inflammation in human umbilical vein endothelial cells (HUVECs)
Summary
Cardiovascular diseases are the leading cause of death worldwide and involve abnormal endothelial cell inflammation [1]. PA was shown to induce activation of NLRP3 (nucleotide oligomerization domain-, leucine-rich repeat- and pyrin domain-containing protein 3) inflammasomes This eventually leads to the production of active caspase-1 [6] that enhances secretion of proinflammatory interleukin-1β (IL1β) to exacerbate local inflammation [7]. Human umbilical vein endothelial cells (HUVECs) were acquired from the Chinese Academy of Sciences (Shanghai, China) and cultured in Ham’s F-12K medium (Upstate Biotechnology, Lake Placid, NY, USA) supplemented with 10% fetal bovine serum (Upstate Biotechnology) and maintained in a 37 °C incubator with 5% CO2. Culture medium from HUVECs pre-treated with or without indicated concentrations of ruscogenin (1, 10, or 30 μM) were collected and centrifuged, and the supernatant levels of IL-1β, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1)were determined by a commercial enzyme-linked immunosorbent assay kits (Thermo Fisher Scientific, Waltham, MA, USA).
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