Abstract
Vasorelaxant and anti-inflammatory effects of a 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) isolated from the root barks of Paeonia suffruticosa and possible mechanisms responsible were investigated. PGG induced a concentration-dependent relaxation of the phenylephrine-precontracted rat aorta. This effect disappeared with the removal of functional endothelium. Pretreatment of the aortic tissues with either N(G)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-alpha]-quinoxalin-1-one (ODQ) inhibited the relaxation induced by PGG. Incubation of human umbilical vein endothelial cells (HUVECs) or carotid arteries isolated from rats with PGG increased the production of cGMP in a dose-dependent manner, but this effect was blocked by pretreatment with L-NAME and ODQ, respectively. PGG treatment attenuated tumor necrosis factor-alpha (TNF-alpha)-induced nuclear factor-kappaB (NF-kappaB) p65 translocation in human umbilical vein endothelial cells. In addition, PGG suppressed the expression levels of adhesion molecules including intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) induced by TNF-alpha. TNF-alpha-induced monocyte chemoattractant protein-1 (MCP-1) expression was also attenuated by addition of PGG. PGG treatment inhibited cellular adhesion of U937 cells onto human umbilical vein endothelial cells induced by TNF-alpha. Taken together, the present study suggests that PGG dilates vascular smooth muscle and suppresses the vascular inflammatory process via endothelium-dependent nitric oxide (NO)/cGMP signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / pharmacology*
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Aorta, Thoracic / drug effects
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Aorta, Thoracic / physiology
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Blotting, Western
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Carotid Arteries / drug effects
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Carotid Arteries / metabolism
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Cell Adhesion / drug effects
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Cell Line
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Chemokine CCL2 / genetics
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Cyclic GMP / biosynthesis
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Cyclic GMP / physiology*
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Dose-Response Relationship, Drug
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Endothelial Cells / drug effects
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Endothelial Cells / metabolism
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Enzyme Inhibitors / pharmacology
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Gene Expression / drug effects
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Guanylate Cyclase / antagonists & inhibitors
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Humans
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Hydrolyzable Tannins / pharmacology*
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In Vitro Techniques
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Intercellular Adhesion Molecule-1 / genetics
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Male
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NF-kappa B / metabolism
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NG-Nitroarginine Methyl Ester / pharmacology
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Nitric Oxide / physiology*
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Nitric Oxide Synthase / antagonists & inhibitors
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Oxadiazoles / pharmacology
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Paeonia / chemistry
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Plant Bark / chemistry
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Plant Roots / chemistry
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Quinoxalines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects*
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Tumor Necrosis Factor-alpha / pharmacology
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U937 Cells
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Umbilical Veins / cytology
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Vascular Cell Adhesion Molecule-1 / genetics
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Vasodilation / drug effects
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Vasodilator Agents / pharmacology*
Substances
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1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
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Anti-Inflammatory Agents
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CCL2 protein, human
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Chemokine CCL2
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Enzyme Inhibitors
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Hydrolyzable Tannins
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NF-kappa B
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Oxadiazoles
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Quinoxalines
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Tumor Necrosis Factor-alpha
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Vascular Cell Adhesion Molecule-1
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Vasodilator Agents
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Intercellular Adhesion Molecule-1
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Nitric Oxide
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pentagalloylglucose
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Nitric Oxide Synthase
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Guanylate Cyclase
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Cyclic GMP
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NG-Nitroarginine Methyl Ester