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• W1985914009 endingPage "165" @default.
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• W1985914009 abstract "Vascular cell adhesion molecule-1 (VCAM-1) is involved in several diseases, including chronic inflammation and atherosclerosis. Inhibition of the expression of this adhesion molecule is one of the key targets of anti-inflammatory, anti-cancer and anti-atherosclerotic drugs. Gynostemma pentaphyllum is a traditional medicine widely used in the treatment of respiratory inflammation, hyperlipidemia and atherosclerosis. However, its molecular mechanisms of action are still largely unknown. Gypenoside XLIX, a dammarane-type glycoside, is a prominent component of G. pentaphyllum. We have recently demonstrated Gypenoside XLIX to be a selective peroxisome proliferator-activated receptor (PPAR)-α activator. Here we demonstrate that Gypenoside XLIX concentration-dependently (0–300 μM) inhibited VCAM-1 promoter activity after induction by cytokine tumor necrosis factor (TNF)-α in human umbilical vein endothelial cells (HUVECs) transfected with promoter–reporter construct pVCAM-1-LUC. Furthermore, Gypenoside XLIX inhibited TNF-α-induced VCAM-1 mRNA and protein overexpression in HUVECs. The result of the enzyme immunoassay demonstrated that Gypenoside XLIX inhibited TNF-α-induced increase in cell surface VCAM-1 protein levels in HUVECs. In the present study we show that activities of Gypenoside XLIX are similar to those of Wy-14643, a potent synthetic PPAR-α activator. Furthermore, Gypenoside XLIX-induced inhibition on TNF-α-stimulated VCAM-1 promoter hyperactivity was completely abolished by a selective blocker of PPAR-α, MK-886. Thus, our findings suggest that Gypenoside XLIX inhibits cytokine-induced VCAM-1 overexpression and hyperactivity in human endothelial cells via a PPAR-α-dependent pathway. These data provide new insight into the rational basis of the use of the traditional Chinese herbal medicine G. pentaphyllum in the treatment of inflammatory and cardiovascular diseases, including atherosclerosis." @default.
• W1985914009 created "2016-06-24" @default.
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• W1985914009 date "2007-06-01" @default.
• W1985914009 modified "2023-10-14" @default.
• W1985914009 title "Gypenoside XLIX, a naturally occurring PPAR-α activator, inhibits cytokine-induced vascular cell adhesion molecule-1 expression and activity in human endothelial cells" @default.
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• W1985914009 doi "https://doi.org/10.1016/j.ejphar.2007.03.013" @default.
• W1985914009 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17434475" @default.
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