Pinocembrin (5,7-dihydroxyflavanone) is one of the primary flavonoids in propolis. Angiotensin II (AngII) is a biologically active peptide that induces vasoconstriction via the activation of the angiotensin type 1 receptor (AT(1)R). In the present study, we investigated the vasorelaxant effect of pinocembrin on AngII-induced vasoconstriction and the molecular mechanism of action. Pinocembrin was observed to inhibit AngII-induced vasoconstriction in rat aortic rings with either intact or denuded endothelium. In endothelium-denuded tissues, pinocembrin (pD(2)' 4.28 +/- 0.15) counteracted the contractions evoked by cumulative concentrations of AngII. In a docking model, pinocembrin showed effective binding at the active site of AT(1)R. Pinocembrin was shown to inhibit both AngII-induced Ca2+ release from internal stores and Ca2+ influx. Moreover, the increase in the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and myosin light chain 2 (MLC2) induced by AngII was blocked by pinocembrin. These results demonstrate that pinocembrin inhibits AngII-induced rat aortic ring contraction, and these inhibitory effects may be related to the reduction of the AngII-induced increase in [Ca2+](i); and ERK1/2 activation via blocking AT(1)R. (C) 2013 Elsevier Inc. All rights reserved.