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.
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.
Kang
Dae Gill
DG
Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
Moon
Mi Kyoung
MK
Choi
Deok Ho
DH
Lee
Jun Kyoung
JK
Kwon
Tae Oh
TO
Lee
Ho Sub
HS
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*
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