Clinical observations have revealed that non-resolving low-grade
inflammation is linked to the pathogenesis of chronic inflammatory diseases, for example
arthritis,
atherosclerosis,
Alzheimer's disease, diabetes, and
chronic kidney disease. Interestingly, low levels of circulating
lipopolysaccharides (LPS) derived from the outer membrane of gram-negative bacteria appear to be one of the primary causes of persistent low-grade
inflammation. The inner surface of the blood vessels is lined with endothelial cells; therefore, even low levels of circulating LPS can directly activate these cells and elicit specific cellular responses, such as an increase in the expression levels of
cell adhesion molecules and proinflammatory mediators. In endothelial cells, LPS exposure results in an inflammatory response through activation of
nuclear factor-kappa B (NF-κB) and
mitogen-activated protein kinases.
Cynarin, a
phytochemical found in artichokes, has several pharmacological properties against endothelial
inflammation. In the present study, we discovered that
cynarin suppressed the LPS-induced increase in the expression levels of
vascular cell adhesion molecule-1 and proinflammatory mediators such as
monocyte chemoattractant protein-1 (MCP-1),
tumor necrosis factor-α (TNF-α), and interleukin-1β in EA.hy926 cells. Further,
cynarin inhibited the activation of p38 and NF-κB pathways by inducing the negative regulator
mitogen-activated protein kinase phosphatase 3 (MKP-3) in LPS-stimulated EA.hy926 cells. In conclusion,
cynarin alleviates
inflammation by upregulating MKP-3, a negative regulator of p38 and NF-κB, and it may be a therapeutic option for treating endothelial
inflammation-related diseases.