Nectandrin B suppresses the expression of adhesion molecules in endothelial cells: Role of AMP-activated protein kinase activation

• Published in: Food and chemical toxicology 2014-04, Vol.66, p.286-294
• Main Authors: Hien, Tran Thi, Ki, Sung Hwan, Yang, Jin Won, Oh, Won Keun, Kang, Keon Wook
• Format: Article
• Language: English
• Subjects: Adhesion molecules; AMP-Activated Protein Kinases - metabolism; AMPK; Biological and medical sciences; Cell Adhesion Molecules - antagonists & inhibitors; Cell Line; Cyclooxygenase 2 - metabolism; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - enzymology; Enzyme Activation; Food toxicology; Humans; Lignans - pharmacology; Medical sciences; Nectandrin B; Nitric Oxide Synthase Type II - metabolism; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2014.01.052

•Nectandrin B inhibited TNFα-induced monocyte adhesion to endothelial cells.•Nectandrin B inhibited expression of adhesion molecules and inflammatory enzymes.•Nectandrin B suppressed the activities of NF-κB, CREB and AP-1.•AMPK activation is required for CREB inhibition by nectandrin B. We have previously shown that nectandrin B, a potent natural activator of AMP-activated protein kinase (AMPK) results in endothelium-dependent relaxation via endothelial nitric oxide synthase phosphorylation. This study examined the effects of nectandrin B on monocyte adhesion and on the expression of adhesion molecules in endothelial cells, an initial event in atherogenesis. Nectandrin B inhibited tumor necrosis factor-α (TNFα)-induced monocytoid THP-1 cell adhesion to ECV 304 human endothelial cells. This lignan also suppressed TNFα-induced protein and mRNA expression of two cell adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1). In addition, expression of cyclooxygenase-2 and inducible nitric oxide synthase were diminished by nectandrin B treatment. Reporter gene and immunoblot analyses revealed that transcription factor activities of nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and cyclic AMP response element binding protein (CREB) were inhibited by nectandrin B. Moreover, nectandrin B activated AMP-activated protein kinase (AMPK) in ECV 304 cells. Transfection of a dominant-negative mutant form of AMPK (DN-AMPK) partially reversed inhibitory effects of nectandrin B on the expression of VCAM-1 and ICAM-1, and on the transcriptional activity of CREB.