title: Vasodilatory and anti-inflammatory effects of the 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) via a nitric oxide-cGMP pathway.
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.
authors.affiliation: Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Dae Gill
authors.initials: DG
authors.lastname: Kang
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Moon
authors.forename: Deok Ho
authors.initials: DH
authors.lastname: Choi
authors.forename: Jun Kyoung
authors.initials: JK
authors.lastname: Lee
authors.forename: Tae Oh
authors.initials: TO
authors.lastname: Kwon
authors.forename: Ho Sub
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics; D006152:Cyclic GMP / Q000096:biosynthesis / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D029596:Paeonia / Q000737:chemistry; D024301:Plant Bark / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D016328:NF-kappa B; D010069:Oxadiazoles; D011810:Quinoxalines; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C435084:pentagalloylglucose; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester