PMID- 16253226 OWN - NLM STAT- MEDLINE DCOM- 20060105 LR - 20220726 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 524 IP - 1-3 DP - 2005 Nov 7 TI - 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. PG - 111-9 AB - 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. FAU - Kang, Dae Gill AU - Kang DG AD - Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea. FAU - Moon, Mi Kyoung AU - Moon MK FAU - Choi, Deok Ho AU - Choi DH FAU - Lee, Jun Kyoung AU - Lee JK FAU - Kwon, Tae Oh AU - Kwon TO FAU - Lee, Ho Sub AU - Lee HS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051025 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one) RN - 0 (Anti-Inflammatory Agents) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Enzyme Inhibitors) RN - 0 (Hydrolyzable Tannins) RN - 0 (NF-kappa B) RN - 0 (Oxadiazoles) RN - 0 (Quinoxalines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 0 (Vasodilator Agents) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 31C4KY9ESH (Nitric Oxide) RN - 3UI3K8W93I (pentagalloylglucose) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 4.6.1.2 (Guanylate Cyclase) RN - H2D2X058MU (Cyclic GMP) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Aorta, Thoracic/drug effects/physiology MH - Blotting, Western MH - Carotid Arteries/drug effects/metabolism MH - Cell Adhesion/drug effects MH - Cell Line MH - Chemokine CCL2/genetics MH - Cyclic GMP/biosynthesis/*physiology MH - Dose-Response Relationship, Drug MH - Endothelial Cells/drug effects/metabolism MH - Enzyme Inhibitors/pharmacology MH - Gene Expression/drug effects MH - Guanylate Cyclase/antagonists & inhibitors MH - Humans MH - Hydrolyzable Tannins/*pharmacology MH - In Vitro Techniques MH - Intercellular Adhesion Molecule-1/genetics MH - Male MH - NF-kappa B/metabolism MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Nitric Oxide/*physiology MH - Nitric Oxide Synthase/antagonists & inhibitors MH - Oxadiazoles/pharmacology MH - Paeonia/chemistry MH - Plant Bark/chemistry MH - Plant Roots/chemistry MH - Quinoxalines/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction/*drug effects MH - Tumor Necrosis Factor-alpha/pharmacology MH - U937 Cells MH - Umbilical Veins/cytology MH - Vascular Cell Adhesion Molecule-1/genetics MH - Vasodilation/drug effects MH - Vasodilator Agents/*pharmacology EDAT- 2005/10/29 09:00 MHDA- 2006/01/06 09:00 CRDT- 2005/10/29 09:00 PHST- 2005/04/14 00:00 [received] PHST- 2005/08/18 00:00 [revised] PHST- 2005/08/29 00:00 [accepted] PHST- 2005/10/29 09:00 [pubmed] PHST- 2006/01/06 09:00 [medline] PHST- 2005/10/29 09:00 [entrez] AID - S0014-2999(05)00895-2 [pii] AID - 10.1016/j.ejphar.2005.08.061 [doi] PST - ppublish SO - Eur J Pharmacol. 2005 Nov 7;524(1-3):111-9. doi: 10.1016/j.ejphar.2005.08.061. Epub 2005 Oct 25.