Abstract: This study utilized streptozotocin to create a diabetic mouse model to investigate the role of intelectin 1 (ITLN1) in repairing the aortic endothelial cells of diabetic mice, and it also identified linarin as dietary ITLN1 agonist and evaluated the protective effect of linarin on endothelial cells. Results showed that the expression of ITLN1 in the aortic endothelial cells of diabetic mice decreased by (66.68 ± 9.51)%. When the ITLN1 gene was knocked down in endothelial cells, the production of reactive oxygen species (ROS) increased with the decline in ITLN1 expression. Subsequently, after administration of linarin at a dose of 50 mg/kg for 28 days, the expression of ITLN1 in the aortic endothelial cells increased compared to the diabetic control group, ROS levels decreased, and the inflammatory factors tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 were downregulated to some extent. Furthermore, mechanistic studies revealed that linarin could inhibit the nicotinamide adenine dinucleotide phosphate oxidase 4 and NF-κB, thereby reducing ROS production and the expression of inflammatory factors, attenuating vascular endothelial injury. Thus, this study proposes that linarin can alleviate endothelial dysfunction in diabetes by targeting ITLN1.

Key words: linarin; diabetes; intelectin 1; aortic endothelial injury; oxidative stress