Avenanthramide C From Oats Possibly Exerts Anti-Inflammatory Effects in Human Umbilical Vein Endothelial Cells

Abstract

Chronic kidney disease (CKD) is associated with inflammation and cardiovascular complications and is partly exacerbated by the uremic toxin indoxyl sulfate (IS). IS is known to activate the aryl hydrocarbon receptor (AhR) to promote vascular inflammation. On the other hand, avenanthramide C (Ave), an oat-derived polyphenol, has antioxidative and anti-inflammatory properties. Therefore, we investigated whether Ave can suppress IS-induced inflammatory responses. Analysis of serum from hemodialysis patients revealed a significant correlation between IS and interleukin-6 (IL-6) levels. In human umbilical vein endothelial cells (HUVECs), IS (≥50 µg/mL) increased IL-6 secretion, while Ave (≥10 µM) suppressed this effect. Docking simulations and in vitro experiments suggested that Ave may interact with AhR and suppress IS-induced expression of AhR target genes, including that of cytochrome P450 family 1 subfamily A member 1. High-performance liquid chromatography verified the uptake of Ave by human umbilical vein endothelial cells. Additionally, the anti-inflammatory effects of Ave were independent of the adrenergic α1 receptor, adenosine monophosphate-activated protein kinase pathways, and protein kinase B pathways. Ave suppresses IS-induced inflammation, thereby reducing IL-6 secretion in HUVECs. These findings suggest the potential of Ave as a dietary intervention for mitigating vascular inflammation in patients with CKD.