Potential anti-inflammatory effect of L-carvone in endothelial dysfunction triggered by uremia related to chronic kidney disease

Abstract Background Chronic kidney disease (CKD) is one of the leading causes of endothelial dysfunction and directly associated with the development of cardiovascular diseases (CVD). The accumulation of uremic toxins stimulates development of an exacerbated inflammatory state, especially in the vascular endothelial microenvironment. L-carvone (CRV) monoterpene is a natural product with several described biological activities, including atheroprotective and anti-inflammatory effects. This study aimed to investigate the in vitro anti-inflammatory effect of CRV on human endothelial cells exposed to hemodialysis patients’ serum. Methods And Results CRV did not affect endothelial cell viability at a concentration of 100 µM, either alone or in combination with uremic serum (US), but it induced a significant increase in cell proliferation ( P < 0.05). CRV significantly reduced the gene ( P < 0.05) and protein ( P < 0.01) expression of Interleukin (IL) 1β (IL-1β) under uremic conditions. CRV also significantly decreased protein levels of other inflammatory biomarkers such as IL-6, IL-8, vascular endothelial growth factor (VEGF-A), serum amyloid A (SAA) ( P < 0.01) and tumor necrosis factor α (TNF-α) ( P < 0.05) in uremic conditions. Monocyte chemoattractant protein 1 (MCP-1) production was additionally reduced ( P < 0.01) and consequently monocyte migration was reduced ( P < 0.05) with CRV under uremic conditions. Cell morphology appeared to remain unchanged in the presence of CRV, and it reduced the cellular damage in the uremic environment caused by uremia. Conclusions Altogether, these findings suggest the beneficial anti-inflammatory effect of CRV in the vascular environment in response to uremic damage in CKD patients, opening perspectives for the study of new targets to better understand the endothelial protection mechanisms.