title: Effect of short-term polyphenol treatment on endothelial dysfunction and thromboxane A2 levels in streptozotocin-induced diabetic mice.
abstract: Diabetes is characterized by the development of endothelial dysfunction, which affects both nitric oxide (NO)-mediated relaxation and endothelium-derived contracting factors, associated with vascular oxidative stress. There is a growing body of evidence suggesting that polyphenols have several beneficial effects, such as antioxidant and anti-inflammatory activities. This study investigated whether short-term treatment with polyphenols (chlorogenic acid (CA), morin (MO), resveratrol (RV)) can improve endothelial dysfunction related to diabetes. Aorta reactivity was determined in organ chambers, and we measured NO production and thromboxane B2 (TXB2; a metabolite of TXA2) from aortas in response to acetylcholine (ACh). Streptozotocin (STZ)-induced diabetic mice (16 weeks) were injected with solvent (ethanol, 10% v/v; intraperitoneally (i.p.)), CA (0.03 mmol/kg/d), MO (0.03 mmol/kg/d), and RV (0.03 mmol/kg/d) for 5 d. The ACh-induced endothelium-dependent relaxation was markedly reduced in rings of STZ-induced diabetic mice compared to controls. The treatment with polyphenols (significantly: MO, tendency: CA and RV) for only 5 d improved the NO components of relaxation, but did not normalize ACh-stimulated NO production. However, polyphenol treatment suppressed the ACh-stimulated level of TXB2 in aortas from STZ-induced diabetic mice. Thus, treatment with polyphenols caused basal NO production and a prompt improvement of the endothelial function in diabetic mice, and this may involve the normalization of TXA2 levels, not NO production, under ACh stimulation.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Taguchi
authors.forename: Mari
authors.initials: M
authors.lastname: Hida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ikeuchi-Takahashi
authors.forename: Hiraku
authors.initials: H
authors.lastname: Onishi
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008813:Mice, Inbred ICR; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D059808:Polyphenols / Q000008:administration & dosage / Q000627:therapeutic use*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use; D013311:Streptozocin; D013928:Thromboxane A2 / Q000378:metabolism*; D047309:Flavones
chemical_list: D000975:Antioxidants; D002726:Chlorogenic Acid; D045462:Endothelium-Dependent Relaxing Factors; D005419:Flavonoids; D009569:Nitric Oxide; D059808:Polyphenols; D000077185:Resveratrol; D013267:Stilbenes; D013311:Streptozocin; D013928:Thromboxane A2; C008548:morin; D047309:Flavones