Pinocembrin inhibits angiotensin II-induced vasoconstriction via suppression of the increase of [Ca2+]i and ERK1/2 activation through blocking AT1R in the rat aorta

• Pinocembrin inhibits AngII-induced contraction of rat aortic rings.
• Pinocembrin displays noncompetitive antagonism of AngII-induced contractions.
• Pinocembrin shows effective binding at the active site of AT1R in a docking model.
• Blockade of [Ca2+]i increase and ERK1/2 activation contributes to the inhibition.
• Pinocembrin inhibits AngII-induced vasoconstriction via AngII-AT1R-Ca2+-ERK pathway.

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 (AT1R). 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 (pD́′2pD2′ 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 AT1R. 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 AT1R.