Plant polyphenols Morin and Quercetin rescue nitric oxide production in diabetic mouse aorta through distinct pathways - 28/08/20
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Graphical abstract |
Highlights |
• | Two structurally similar polyphenols activate distinct signaling pathway. |
• | MO activates Akt/eNOS signaling pathway independent of PI3K and AMPK. |
• | In Control, QU activates PI3K/Akt/eNOS signaling pathway, independent of AMPK. |
• | In DM, QU activates eNOS via the PI3K/Akt and AMPK signaling pathways. |
Abstract |
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.
El texto completo de este artículo está disponible en PDF.Keywords : Diabetes, Endothelial dysfunction, eNOS, Morin, Quercetin
Esquema
Vol 129
Artículo 110463- septembre 2020 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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