Summary

Nectandrin B Suppressed TNFa-Induced Expression of Pro-Inflammatory Activities and Cell Adhesion Molecules in Human Endothelial Cells

Nectandrin B suppressed the tumor necrosis factor-a (TNFa)-induced protein and mRNA expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), cell adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1), which is a key early event in atherogenesis. Expression of TNFa was also inhibited by nectandrin B. Reporter gene analyses revealed that minimal reporter activities of nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) were blocked by nectandrin B in a concentration-dependent manner. Nectandrin B treatment decreased TNFa- induced nuclear level of cyclic AMP response element binding protein (CREB) but not of p65 and CCAAT/enhancer binding protein (C/EBP)α/β protein levels. Transfection of constitutively active dominant negative (DN-AMPK, that depletes endogenous AMPKα) reversed its effect on CREB protein level and CRE luciferase activity. The results indicate that nectandrin B may have anti-inflammatory and anti-atherosclerotic activities in vasculatures, which occurs partly by down-regulating the expression of cell adhesion molecules and pro-inflammatory cytokines in endothelial cells through inhibition of AMPK pathway.

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