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

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 NG-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.