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 NG-nitro-l-arginine methyl ester (L-NAME), methylene blue, or 1H-[1,2,4]-oxadiazole-[4,3-α]-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-α-induced NF-κB 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-α in HUVECs. TNF-α-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-α. Taken together, the present study suggests that AR dilates vascular smooth muscle and suppresses the vascular inflammatory process via endothelium-dependent NO/cGMP signaling.