title: Pinocembrin inhibits angiotensin II-induced vasoconstriction via suppression of the increase of [Ca2+]i and ERK1/2 activation through blocking AT(1)R in the rat aorta.
abstract: 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 Ca(2+) release from internal stores and Ca(2+) 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 [Ca(2+)]i and ERK1/2 activation via blocking AT1R.
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xian Nong Tan Street, Beijing 100050, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Pang
authors.forename: Bai-Nian
authors.initials: BN
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.forename: Shou-Bao
authors.initials: SB
authors.lastname: Wang
authors.forename: Su-Bo
authors.initials: SB
authors.lastname: Wang
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D024722:Cardiac Myosins / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D044950:Flavanones / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044950:Flavanones; D018994:Myosin Light Chains; D044140:Receptor, Angiotensin, Type 1; C107184:myosin light chain 2; D000804:Angiotensin II; C016063:pinocembrin; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D024722:Cardiac Myosins; D002118:Calcium