Effect of (R)-(−)-Linalool on endothelial damage: Sex differences

Abstract

Oxidative stress and inflammation are responsible for endothelial damage displaying many sex differences. Lipopolysaccharide (LPS) is a pathogenic stimulus that can trigger inflammation, contributing to endothelial dysfunction. Given the scientific evidence on the effectiveness of herbal extracts in managing endothelial dysfunction, we considered the (R)-(−)-Linalool (LIN), an aromatic monoterpene alcohol, as a bioactive phytochemical compound that could prevent and improve endothelial injury. In this study, we evaluated the effect of the LIN on LPS-induced damage in female and male human umbilical vein endothelial cells (FHUVECs and MHUVECs), measuring cell viability, cytokines release (IL-6 and TNF-α), malondialdehyde (MDA), and nitrites.LPS significantly reduced viability both in MHUVECs and FHUVECs. Moreover, LPS increased the IL-6, TNF-α, and MDA level only in FHUVECs if compared to basal value; despite that, LPS reduced nitrites only in MHUVECs. LIN alone did not affect the parameters measured except for an increase in nitrites in FHUVECs. Nevertheless, LIN reduced damage and restored endothelium viability reduced by LPS without a clear sex difference. Under LPS, LIN inhibited IL-6 release and reduced MDA levels only in FHUVECs.The present data confirm the existence of sex differences in the behavior of HUVECs under LPS conditions. The administration of LIN seems to have a more evident effect on FHUVECs after damage induced by LPS. These LIN effects are important to conduct further well-designed studies on the sex-specific use of this compound on vascular endothelial injury.

Keywords

• Endothelial cells
• Lipopolysaccharide
• Sex differences
• Endothelial damage
• (R)-(−)-Linalool