Vasodilatory and anti-inflammatory effects of the aqueous extract of rhubarb via a NO-cGMP pathway.
While conducting an in vitro screen of various medicinal plant extracts, an aqueous extract of rhubarb (Rheum undulatum L, AR) was found to exhibit a distinct vasorelaxant activity. AR induced a concentration-dependent relaxation of the phenylephrine-precontracted aorta. This effect disappeared with the removal of functional endothelium. Pretreatment of the aortic tissues with N(G)-nitro-L-arginine methyl ester (L-NAME), methylene blue, or 1H-[1,2,4]-oxadiazole-[4,3-alpha]-quinoxalin-1-one (ODQ) inhibited the relaxation induced by AR. Incubation of human umbilical vein endothelial cells (HUVECs) with AR increased the production of cGMP in a dose-dependent manner, but this effect was blocked by pretreatment with L-NAME and ODQ, respectively. AR treatment attenuated TNF-alpha-induced NF-kappaB p65 translocation in HUVECs in a dose-dependent manner. In addition, AR suppressed the expression levels of adhesion molecules including ICAM-1 and VCAM-1 induced by TNF-alpha in HUVECs. TNF-alpha-induced MCP-1 expression was also attenuated by the addition of AR. This attenuation was blocked by pretreatment with either L-NAME or ODQ. AR treatment inhibited cellular adhesion of U937 cells onto HUVECs induced by TNF-alpha. Taken together, the present study suggests that AR dilates vascular smooth muscle and suppresses the vascular inflammatory process via endothelium-dependent NO/cGMP signaling.
Moon
Mi Kyoung
MK
Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea.
Kang
Dae Gill
DG
Lee
Jun Kyong
JK
Kim
Jin Sook
JS
Lee
Ho Sub
HS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012250:Rheum / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D006152:Cyclic GMP