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The vascular relaxant effect of the rhizome extract ofRheum undulatumwas evaluated with isolated rat thoracic aorta preparations. The methanol extract of the rhizome induced a concentration-dependent relaxation of aortic preparations precontracted with 0.3 μM phenylephrine (EC50 value: 5.8 μg/mL). The activity-guided fractionation of the extract led to the isolation of seven hydroxystilbene components as active principles, i.e. piceatannol, resveratrol, desoxyrhapontigenin, rhapontigenin, piceid, rhaponticin and £ -viniferin. Of these, piceatannol, a tetrahydroxystilbene, exhibited the most potent vascular relaxant effect in rat aortic preparations (EC50 value 2.4 μM). The vasorelaxant effect of piceatannol on endothelium-intact aorta rings was diminished completely by the removal of functional endothelium or by pretreatment of the aortic tissues with NG-nitro-L-arginine methyl ester. These results suggest that piceatannol may be the major mediator responsible for the vasorelaxing properties of the rhizome extract ofRheum undulatumand the vasorelaxant effects of the piceatannol may be mediated via endothelium-dependent nitric oxide signaling pathway. Copyright © 2006 John Wiley & Sons, Ltd.