Ginsenoside Rb1 Inhibits Tumor Necrosis Factor-.ALPHA.-Induced Vascular Cell Adhesion Molecule-1 Expression in Human Endothelial Cells
- 1 January 2008
- journal article
- Published by Pharmaceutical Society of Japan in Biological & Pharmaceutical Bulletin
- Vol. 31 (11), 2050-2056
- https://doi.org/10.1248/bpb.31.2050
Abstract
We investigated whether ginsenoside Rb1 (Rb1) could block tumor necrosis factor-alpha (TNF-alpha)-induced over-expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and human lung microvascular endothelial cells (HMVECs-L). Cells were treated with various concentrations of TNF-alpha with or without Rb1 pre-treatment for 16 h. The mRNA and protein levels of VCAM-1 were determined with real-time polymerase chain reaction (PCR) and flow cytometry, respectively. Human monocytic THP-1 cells labeled with fluorescent dye (Calcein-AM) was used for the adhesion assay on HUVEC monolayers. Dihydroethidium (DHE) was used to demonstrate in situ levels of superoxide production. JC-1 dye was used to measure changes in mitochondrial membrane potential. Activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) was determined by Bio-Plex immunoassay. TNF-alpha treatment significantly increased the mRNA and protein levels of VCAM-1 in HUVECs in a dose dependent manner. Rb1 pre-treatment effectively blocked the TNF-alpha-induced expression of VCAM-1 mRNA or protein by 80% and 43%, respectively (p<0.01). THP-1 adhesion was also blocked. Furthermore, Rb1 reduced the TNF-alpha-induced increase of superoxide anion production by 41% and inhibited the TNF-alpha-induced decrease of mitochondrial membrane potential by 44% in HUVECs. Rb1 also effectively blocked TNF-alpha-induced activation of p38, c-Jun N-terminal protein kinase, extracellular signal-regulated kinase 1/2 and IkappaBalpha. In conclusion, Rb1 effectively blocked the TNF-alpha-induced over-expression of VCAM-1, increased THP-1 adhesion and over-production of superoxide anion. Furthermore, Rb1 inhibited TNF-alpha-induced MAPKs and NF-kappaB activation. These data suggested that Rb1 might have potential therapeutic effects in controlling inflammation in vascular diseases.Keywords
This publication has 25 references indexed in Scilit:
- Localizing NADPH Oxidase–Derived ROSScience's STKE, 2006
- Activation of the canonical Wnt/β-catenin pathway enhances monocyte adhesion to endothelial cellsBiochemical and Biophysical Research Communications, 2006
- Cytokine-induced monocyte adhesion to endothelial cells involves platelet-activating factor: Suppression by conjugated linoleic acidBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2006
- Mitogen-activated protein kinase (MAPK)Critical Care Medicine, 2005
- Inhibitory Effects of Ginsenoside-Rb1 on Activation of the 12-O-Tetradecanoylphorbol 13-Acetate-Induced Cyclooxygenase-2 PromoterPlanta Medica, 2005
- Inflammation, Atherosclerosis, and Coronary Artery DiseaseThe New England Journal of Medicine, 2005
- Improvement of Function and Morphology of Tumor Necrosis Factor-.ALPHA. Treated Endothelial Cells With 17-.BETA. Estradiol A Preliminary Study for a Feasible Simple Model for AtherosclerosisCirculation Journal, 2005
- Discovery of Novel Phenolic Antioxidants as Inhibitors of Vascular Cell Adhesion Molecule-1 Expression for Use in Chronic Inflammatory DiseasesJournal of Medicinal Chemistry, 2004
- ROS: A Step Closer to Elucidating Their Role in the Etiology of Light-Induced Skin DisordersJournal of Investigative Dermatology, 2004
- RORα1 and RORα4 suppress TNF-α-induced VCAM-1 and ICAM-1 expression in human endothelial cellsFEBS Letters, 2003