Ginsenoside Rb1 Inhibits Tumor Necrosis Factor-α-Induced Vascular Cell Adhesion Molecule-1 Expression in Human Endothelial Cells(Pharmacology)
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概要
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We investigated whether ginsenoside Rb1 (Rb1) could block tumor necrosis factor-alpha (TNF-α)-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-α with or without Rb1 pre-treatment for 16h. 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-κB (NF-κB) was determined by Bio-Plex immunoassay. TNF-α 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-α-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-α-induced increase of superoxide anion production by 41% and inhibited the TNF-α-induced decrease of mitochondrial membrane potential by 44% in HUVECs. Rb1 also effectively blocked TNF-α-induced activation of p38, c-Jun N-terminal protein kinase, extracellular signal-regulated kinase 1/2 and IκBα. In conclusion, Rb1 effectively blocked the TNF-α-in-duced over-expression of VCAM-1, increased THP-1 adhesion and over-production of superoxide anion. Furthermore, Rb1 inhibited TNF-α-induced MAPKs and NF-κB activation. These data suggested that Rb1 might have potential therapeutic effects in controlling inflammation in vascular diseases.
- 2008-11-01
著者
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CHAI Hui
College of Life Sciences, Zhejiang University
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WANG Qiuyan
Center for Biomedicine and Health, Hangzhou Normal University
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HUANG Lifeng
Center for Biomedicine and Health, Hangzhou Normal University
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XIE Tian
Center for Biomedicine and Health, Hangzhou Normal University
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FU Yan
College of Life Sciences, Zhejiang University
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Xie Tian
Center For Biomedicine And Health Hangzhou Normal University
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Huang Lifeng
Center For Biomedicine And Health Hangzhou Normal University
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Fu Yan
College Of Life Sciences Zhejiang University:college Of Animal Sciences Zhejiang University
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Wang Qiuyan
Center For Biomedicine And Health Hangzhou Normal University
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Chai Hui
College Of Life Sciences Zhejiang University