title: Nectandrin B suppresses the expression of adhesion molecules in endothelial cells: Role of AMP-activated protein kinase activation.
abstract: 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.
authors: College of Pharmacy, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Tran Thi
authors: TT
authors: Hien
authors: College of Pharmacy, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Sung Hwan
authors: SH
authors: Ki
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Jin Won
authors: JW
authors: Yang
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Won Keun
authors: WK
authors: Oh
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: kwkang@snu.ac.kr.
authors: Keon Wook
authors: KW
authors: Kang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D017705:Lignans; C524653:nectandrin-B; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Adhesion molecules; Endothelial cells; Nectandrin B