title: Dietary polyphenol morin rescues endothelial dysfunction in a diabetic mouse model by activating the Akt/eNOS pathway.
abstract: METHODS
  Endothelial dysfunction is a critical factor during the initiation of diabetic cardiovascular complications. Polyphenols may represent beneficial dietary components eliciting cardiovascular protection. Although we previously reported that the polyphenol morin (MO) ameliorated diabetes-induced endothelial dysfunction, the underlying mechanism remains unclear. Here, we investigated protective effects and mechanisms of MO in streptozotocin STZ induced diabetic aorta endothelial dysfunction.
  
  
  RESULTS
  Diabetes was induced by tail vein injection of STZ (200 mg/kg). At 12 wk after injection, the thoracic aorta was isolated and endothelial function was assessed by acetylcholine (ACh) induced, endothelial-dependent vasorelaxation in aortas. Nitric oxide (NO) levels and endothelial NO synthase (eNOS), phosphorylated-eNOS (p-eNOS), Akt, and phosphorylated-Akt (p-Akt) levels were also evaluated in aortas. Diabetic aortas showed attenuated endothelial function, which was improved by MO treatment. MO treatment alone increased NO levels and endothelial-dependent relaxation responses via Akt signaling, although ACh did not activate this pathway. Moreover, MO upregulated p-Akt (at Ser473 and Thr308) and p-eNOS (at Ser1177) expression in diabetic aortas, but ACh stimulation had no effect on p-Akt and p-eNOS levels.
  
  
  CONCLUSIONS
  These results indicate a novel role for MO in protection against endothelial dysfunction in diabetes. The protective effects of MO are dependent on Akt-dependent activation of eNOS signaling.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Hida
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005419:Flavonoids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013311:Streptozocin; D014664:Vasodilation / Q000187:drug effects; D047309:Flavones
chemical_list: D000109:Acetylcholine; D005419:Flavonoids; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D013311:Streptozocin; C008548:morin; D047309:Flavones; C496315:Nos3 protein, mouse
keywords: Akt; Diabetes; Endothelial dysfunction; Morin; Nitric oxides