| Nuclear factor-κB (NF-κB) existed in all the cells,which plays is an an uclear transcription factor important role in the regulation of many inflammatory genes expression participated in the development of many cardiovasculardiseases,such as atheroselerosis (AS),ischemia-reperfusion injury,Post-infarct ventricular remodeling,ventricular hypertrophy,etc.Isoflavone puerarin [7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one 8-(β-D- glucopyranoside)] is the most abundant isoflavone-C-glucoside extracted from the root of the plant radix puerariae and possesses many biological activities including antioxidation , anticancer and improvement of hyperglycemic disorder . NF-κB activation by puerarin (Pue) affecting Adhesion molecules(AMs) expression in Endothelial cells (ECs) and AS induced by cholesterol diet was not fully clarified. In the present study, interference with NF-κB activation by Pue affecting Adhesion molecules expression in ECs and AS induced by cholesterol diet was investigated, from which further mechanisms were provided to us to understand pleiotropic effects of Pue.PartⅠPuerarin Inhibits Adhesion Molecule Expression in TNF-α-Stimulated Human Endothelial Cells via Modulation of the Nuclear Factor -κB PathwayObjective: In this report, the ability of puerarin to modulate intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial leukocyte adhesion molecule 1 (E-selectin), and to induce changes in the nuclear factor-κB (NF-κB) pathway in human umbilical vein endothelial cells (HUVECs) was examined. Methods: The protein and mRNA levels of tumor necrosis factor-α(TNF-α) -induced ICAM-1, VCAM-1 and E-selectin were determined in HUVEVCs. The inhibitor kappaB (I-κB) phosphorylation and the p65NF-κB expression in HUVECs were also examined. Results: The results indicated that puerarin inhibited the expression of TNF-α-induced ICAM-1, VCAM-1 and E-selectin proteins and mRNAs in HUVECs. Subsequently we determined that the inhibition of ICAM-1, VCAM-1 and E-selectin expression was due to a dose-dependent suppression of phosphorylation and degradation of I-κB, which resulted in a reduction of p65NF-κB nuclear translocation. Conclusion: These data suggested that the effect of puerarin-mediated inhibition ofTNF-α-induced ICAM-1, VCAM-1 and E-selectin expression is attributed to suppressed NF-κB activation in the transcriptional level.PartⅡInhibition of NF-ΚB Activation in Arterial walls in Rabbits with Cholesterol diet by Puerarin Attenuates AtheroselerosisObjective:To study the effect of puerarin (Pue) on NF-κB activation in arterial walls in rabbits with cholesterol diet and its relation to atheroselerosis (AS), the mechanism in AS attenuated by Pue was investigated. Methods: Twenty four male rabbits were randomly divided into the normal diet, and the cholesterol diet and the Pue groups,and was fed for 16 weeks. The protein levels of ICAM-1, VCAM-1 and E-selectin were determined in plasma of rabbits at 0, 8 and 16 weeks . After 16 weeks,the rabbits were put to death and the aortas were harvested for the pathologic morphology observations.The expression of AMs were determined in arterial walls. The inhibitor kappaB (I-κB) phosphorylation and the p65NF-κB expression in arterial walls extract were also examined. Results: Compared with normal diet group, expression of adhesion molecules were significantly increased in cholesterol diet group, p-IκB-аwas obviously increased, IκB-аwas markedly decreased and NF-κB p65 was apparently increased in arterial walls. However, Pue could inhibit formation of atherosclerotic plaques and expression of adhesion molecules in arterial walls induced by cholesterol diet,and they could inhibit p-IκB-аobviously increased, IκB-аmarkedly decreased and NF-κB p56 apparently increased in arterial walls. Conclusion: NF-ΚB activation might be involved in rabbit with cholesterol diet. Pue had an inhibitory effect on AS in rabbit with cholesterol diet, which might be associated with its inhibition of NF-κB activation. |
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