Puerarin inhibits adhesion molecule expression in tnf-alpha-stimulated human endothelial cells via modulation of the nuclear factor kappaB pathway.
BACKGROUND
The isoflavone puerarin is the most abundant isoflavone-C-glucoside extracted from the root (radix puerariae) of the plant Pueraria lobata and possesses many biological activities. 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 kappaB (NF-kappaB) pathway in human umbilical vein endothelial cells (HUVECs) was examined.


METHODS
The protein and mRNA levels of tumor-necrosis-factor-alpha (TNF-alpha)-induced ICAM-1, VCAM-1 and E-selectin were determined in HUVECs. Inhibitor kappaB (I-kappaB) phosphorylation and p65 NF-kappaB expression in HUVECs were also examined.


RESULTS
Puerarin inhibited the expression of TNF-alpha-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-kappaB, which resulted in a reduction of p65 NF-kappaB nuclear translocation.


CONCLUSIONS
These data suggested that the effect of puerarin-mediated inhibition of TNF-alpha-induced ICAM-1, VCAM-1 and E-selectin expression is attributed to suppressed NF-kappaB activation on the transcriptional level.
Hu
Wenzhi
W
Department of Cardiology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Zhang
Qin
Q
Yang
Xiangjun
X
Wang
Yueying
Y
Sun
Lie
L
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D007529:Isoflavones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D029908:Pueraria / Q000737:chemistry; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism
D019040:E-Selectin; D007529:Isoflavones; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C033607:puerarin