title: Natural product extract of Dicksonia sellowiana induces endothelium-dependent relaxations by a redox-sensitive Src- and Akt-dependent activation of eNOS in porcine coronary arteries.
abstract: OBJECTIVE
  The consumption of polyphenol-rich food is associated with a decreased mortality from coronary diseases. This study examined whether a standardized hydroalcoholic extract of Dicksonia sellowiana (HEDS) triggered endothelium-dependent relaxations in porcine coronary artery rings and characterized the underlying mechanism.
  
  
  METHODS
  The phosphorylation level of Src, Akt and eNOS was assessed by Western blot analysis, the formation of reactive oxygen species by dihydroethidine staining and the level of eNOS Ser1177 phosphorylation by immunohistochemical staining in sections of coronary arteries.
  
  
  RESULTS
  HEDS-induced endothelium-dependent relaxations were strongly reduced by Nω-nitro-L-arginine, an eNOS inhibitor, and by its combination with charybdotoxin plus apamin, inhibitors of endothelium-derived hyperpolarizing factor-mediated responses. These relaxations were markedly reduced by MnTMPyP (a membrane-permeant mimetic of superoxide dismutase), polyethylene glycol catalase (PEG-catalase; a membrane-permeant analog of catalase), and by wortmannin (an inhibitor of PI3-kinase). HEDS-induced sustained phosphorylation of Akt and eNOS in endothelial cells was abolished by MnTMPyP, PEG-catalase and wortmannin. Oral administration of HEDS induced a significant decrease of mean arterial pressure in spontaneously hypertensive rats.
  
  
  CONCLUSIONS
  These findings indicate that HEDS caused endothelium-dependent relaxations of coronary artery rings through the redox-sensitive activation of the endothelial PI3-kinase/Akt pathway leading to the subsequent activation of eNOS by phosphorylation. HEDS also has antihypertensive properties.
authors.affiliation: UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France.
authors.forename: Yanna D
authors.initials: YD
authors.lastname: Rattmann
authors.forename: Eric
authors.initials: E
authors.lastname: Anselm
authors.forename: Jong-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dal-Ros
authors.forename: Cyril
authors.initials: C
authors.lastname: Auger
authors.forename: Obdulio G
authors.initials: OG
authors.lastname: Miguel
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
authors.forename: Thierry
authors.initials: T
authors.lastname: Chataigneau
authors.forename: Valérie B
authors.initials: VB
authors.lastname: Schini-Kerth
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000037:antagonists & inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation; D029624:Ferns / Q000737:chemistry*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D034421:Sus scrofa; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D002147:Calmodulin; D010936:Plant Extracts; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2