The Effect And Mechanism Of 7-Methoxyisoflavone On Vascular Endothelial Inflammation

Objective:Endothelial cell inflammation is one of the important causes of many diseases.In this study,by investigating the effect and mechanism of 7Methoxyisoflavone on endothelial cell inflammation,we explore the possibility that this drug can be applied to treat various vascular inflammatory diseases.Method:In this experiment,IL-1β was used to stimulate human umbilical vein endothelial cells to establish endothelial cell inflammation.QPCR and Western blot were used to detect changes of the expression of VC AM-1 and ICAM-1 at mRNA and protein levels with treatment of different concentrations of 7-Mif,and monocyteendothelial cell adhesion assay was also used to detect the effect of 7-Mif on adhesion between monocytes and endothelial cells.As for mechanism,Western blot was used to detect NF-κB signaling pathway related proteins and their phosphorylation degree.Immunofluorescence and nuclear and cytoplasmic protein separation test were used to detect the activation of NF-κB signaling pathway.Dual luciferase reporter gene test was used to measure activity of promoter of ICAM-1 and VCAM-1.Animal model of acute inflammation was established to determine the effect of 7-Mif on endothelial inflammation in vivo.Result:7-Mif can reduce the increasing mRNA and protein levels of ICAM-1 and VCAM-1 in HUVECs caused by IL-1β and can reverse the increasing monocyteendothelial cell adhesion caused by IL-1β stimulation.7-Mif can reduce the phosphorylation of IκB and p65 in HUVECs caused by IL-1β stimulation.As well,immunofluorescence and nuclear and cytoplasmic protein test showed that 7-Mif can suppress p65 transferring into the nucleus.The results of dual luciferase reporter gene experiments showed that 7-Mif can inhibit the enhanced luciferase activity of VCAM1 and ICAM-1 promoter caused by IL-1β.By establishing an animal model of acute inflammation,HE slices show that 7-Mif can reduce neutrophil infiltration and interstitial edema in lung tissue,and can reduce the increased expression of VCAM-1 and ICAM-1 and accumulation of Macrophage in lung tissue.Conclusion:7-Mif can alleviate the inflammatory response of endothelial cells caused by IL-1β stimulation,and this effect is through inhibiting the activation of NF-κB signaling pathway and enhancing expression of VCAM-1 and ICAM-1.At the same time,7-Mif can reduce acute inflammation in animals.