morin and Diabetic-Angiopathies

Diabetic vascular complications are associated with endothelial dysfunction. Various plant-derived polyphenols benefit cardiovascular function by protecting endothelial nitric oxide (NO) production through as yet unclear mechanisms. This study compared the effects of two structurally similar polyphenols, Morin (MO) and Quercetin (QU), on endothelial function in isolated aorta from control and streptozotocin (STZ)-induced diabetic mice. Vascular function under treatment with MO, QU, and various signaling pathway modulators was measured by isometric tension in an organ bath system, NO production by chemical assay and HPLC, and changes in protein signaling factor expression or activity by western blotting (WB). Both polyphenols acted as potent vasodilators and this effect was associated with increased phosphorylation of Akt and endothelial NO synthase (eNOS). An Akt inhibitor blocked MO- and QU-induced vasorelaxation as well as Akt phosphorylation. However, inhibitors of phosphoinositide 3-kinase (PI3K) and AMP-activated protein kinase (AMPK) suppressed only QU-induced vasorelaxation, NO production, and AMPK phosphorylation. These results suggested that plant polyphenols MO and QU both promote eNOS-mediated NO production and vasodilation in diabetic aorta, MO via Akt pathway activation and QU via PI3K/Akt and AMPK pathway activation. Elucidation of these pathways may define effective therapeutic targets for diabetic vascular dysfunction.

Topics: AMP-Activated Protein Kinases; Animals; Aorta; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Enzyme Activation; Flavonoids; Male; Mice, Inbred ICR; Nitric Oxide; Nitric Oxide Synthase Type III; Phosphatidylinositol 3-Kinase; Phosphorylation; Proto-Oncogene Proteins c-akt; Quercetin; Signal Transduction; Vasodilation

The non-enzymatic glycation of Low density lipoprotein (LDL) is a naturally occurring chemical modification of apolipoprotein B as a result of condensation between lysine residues and glucose. Glycated LDL is poorly recognized by LDL receptors and initiates different processes that can be considered proatherogenic. Thus, LDL glycation may contribute in the increased atherosclerotic risk of patients with diabetes. The objective of this study was to investigate the effect of naturally occurring flavonols on LDL glycation in vitro.. In this study, LDL was isolated from EDTA-plasma by ultracentrifugation using a single step discontinuous gradient. Then, glucose was added to LDL and LDL glycation level was estimated in absence and presence of flavonols by sodium periodate assay.. This study was showed that five flavonols: quercetin, myricetin, kaempferol, rutin and morin decreased LDL glycation in a dose-dependent manner. Also, it was demonstrated this nutrients decreased electrophoretic mobility of glycated LDL.. The results of this investigation show that flavonols probably with their antioxidant properties inhibited LDL glycation and thus may have a role in ameliorating atherosclerotic risk of patients with diabetes mellitus.

Topics: Adult; Antioxidants; Atherosclerosis; Diabetic Angiopathies; Flavonoids; Flavonols; Glycation End Products, Advanced; Glycosylation; Humans; In Vitro Techniques; Kaempferols; Lipoproteins, LDL; Male; Quercetin; Rutin