Investigation of the effectiveness of fisetin administration on antiatherogenic and anti-inflammatory parameters in tumour necrosis factor alpha-induced endothelial dysfunction model

Local inflammation seen after endothelial damage is the beginning of atherosclerosis and inflammation has an important role not only at the beginning but also at every stage of the disease. Following activation of the endothelial cell, cytokines, chemokines and adhesion molecules are secreted. In studies conducted to reduce monocyte adhesion and cell damage with various phytochemicals, it has been shown that the expression levels of molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and nuclear factor kappa B (NF-κB) may decrease. Induction of human umbilical vein endothelial cells (HUVEC) with TNF-α constitutes a good model of coronary artery disease. In this study, we aimed to investigate the anti-inflammatory and anti-atherosclerotic activity of fisetin, which has a high anti-inflammatory effect, at the biochemical and molecular level in HUVEC cell line induced with tumour necrosis factor-alpha (TNF-α) and created inflammation and atherosclerosis model. In human umbilical vein endothelial cell culture in which HUVEC cell line was induced with TNF-α and inflammation and atherosclerosis model was created, LD50 concentration of fisetin was applied to each group 6 hours before, simultaneously with and 6 hours after 10 ng/mL TNF-α application. After incubation for 24 hours, nitric oxide, TNF-α, interleukin 1-beta (IL-1β) and IL-10 levels in endothelial cells were measured by ELISAmetric method, and the expression of ICAM-1, VCAM-1 and NF-κB proteins were measured by Western blotting. Analyses were performed using SPSS for Windows v16.0 package programme. Nitric oxide, TNF-α and IL-1β levels and the expressions of ICAM-1, VCAM-1 and NF-κB proteins were increased in the TNF-α treated group (p<0.05). A statistically significant decrease in these parameters was observed in all three groups treated with fisetin compared to the TNF-α-treated group (p<0.05). IL-10 level did not change with TNF-α treatment (p>0.05) but increased with TNF-α and fisetin treatment (p<0.05). TNF-α administration increased the levels of inflammatory parameters in HUVEC cells, indicating that endothelial damage model was formed. The decrease in the levels of inflammatory parameters by fisetin administration together with TNF-α indicates that fisetin may have therapeutic and prophylactic effect on inflammation and endothelial damage development.