L-Tetrahydropalamatine Inhibits Tumor Necrosis Factor-α-Induced Monocyte-Endothelial Cell Adhesion through Downregulation of Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 Involving Suppression of Nuclear Factor-κ B Signaling Pat

摘要

Objective:To investigate whether I-tetrahydropalmatine(I-THP),an alkaloid mainly present in Corydalis family,could ameliorate early vascular inflammatory responses in atherosclerotic processes.Methods:Fluorescently labeled monocytes were co-incubated with human umbilical vein endothelial cells(HUVECs),which were pretreated with I-THP and then simulated with tumor necrosis factor(TNF)-α in absence of I-THP to determine if I-THP could reduce thecytokine-induced adhesion of monocytes to HUVECs.Then I-THP were further studied the underlying mechanisms through observing the transcriptional and translational level of intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) and the nuclear translocation of nuclear factor(NF)-k B in HUVECs.Results:L-THP could block TNF-α-induced adhesion of monocytes to HUVECs and could significantly inhibited the expression of ICAM-1 and VCAM-1 on cell surface by 31%and36%at 30 μ mol/L.L-THP pretreatment could also markedly reduce transcriptional and translational level of VCAM-1 as well as mildly reduce the total protein and mRNA expression levels of ICAM-1.Furthermore,I-THP attenuated TNF-α-stimulated NF-k B nuclear translocation.Conclusion:These results provide evidences supporting that I-THP could be a promising compound in the prevention and treatment of the early vascular inflammatory reaction in atherosclerosis by inhibiting monocyte adhesion to vascular endothelial cell through downregulating ICAM-1 and VCAM-1 in vascular endothelial cell based on suppressing NF-k B.