Vasodilatory and anti-inflammatory effects of the 1,2,3,4,6-penta- O-galloyl-β- d-glucose (PGG) via a nitric oxide–cGMP pathway

• Published in: European journal of pharmacology 2005-11, Vol.524 (1), p.111-119
• Main Authors: Kang, Dae Gill, Moon, Mi Kyoung, Choi, Deok Ho, Lee, Jun Kyoung, Kwon, Tae Oh, Lee, Ho Sub
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Aorta, Thoracic - drug effects; Aorta, Thoracic - physiology; Biological and medical sciences; Blotting, Western; Carotid Arteries - drug effects; Carotid Arteries - metabolism; Cell adhesion; Cell Adhesion - drug effects; Cell Line; Chemokine CCL2 - genetics; Cyclic GMP - biosynthesis; Cyclic GMP - physiology; Dose-Response Relationship, Drug; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Enzyme Inhibitors - pharmacology; Gene Expression - drug effects; Guanylate Cyclase - antagonists & inhibitors; Humans; Hydrolyzable Tannins - pharmacology; In Vitro Techniques; Intercellular Adhesion Molecule-1 - genetics; Male; Medical sciences; NF-kappa B - metabolism; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric oxide/cGMP (guanosine 3′, 5′,-cyclic monophosphate); Oxadiazoles - pharmacology; Paeonia - chemistry; PGG (1,2,3,4,6-penta- O-galloyl-β- d-glucose); Pharmacology. Drug treatments; Plant Bark - chemistry; Plant Roots - chemistry; Quinoxalines - pharmacology; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; Tumor Necrosis Factor-alpha - pharmacology; U937 Cells; Umbilical Veins - cytology; Vascular Cell Adhesion Molecule-1 - genetics; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Vasorelaxation
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.08.061

Vasorelaxant and anti-inflammatory effects of a 1,2,3,4,6-penta- O-galloyl-β- 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-α]-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-α (TNF-α)-induced nuclear factor-kappaB (NF-κB) 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-α. TNF-α-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-α. 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.