Dihydromyricetin protects against high glucose-induced endothelial dysfunction: Role of HIF-1α/ROR2/NF-κB

Abstract

Objectives: Dihydromyricetin (DHM), a natural flavonoid isolated from vine tea with anti-inflammatory activity was evaluated for its ability to prevent vascular endothelial dysfunction caused by hyperglycaemia.

Methods: Vasoconstrictor (phenylephrine-PE) and vasodilator (acetylcholine-ACh) responses were monitored for female rat aorta rings maintained in a bioassay organ bath for 3 h at 37 °C in either low (LG: 10 mM) or high (HG: 40 mM, to mimic hyperglycaemia) glucose-Krebs buffer in the absence or presence of 50 µM DHM. Tissues recovered from the organ bath at 3 h were fixed and analyzed for morphological changes and their expression of eNOS, iNOS, HIF-1α, GLUT1, ROR2 tyrosine kinase, NF-κB, TNF-α, Bax, Bcl2, caspase-3, and forindices of increased oxidative stress.

Key findings: HG-incubated tissues showed increased PE-stimulated contractile response and decreased ACh-mediated endothelial vasodilation. DHM prevented both of these changes. Besides, HG incubation increased the immunoreactivity to iNOS, HIF-1α, GLUT1, ROR2, NF-κB, TNF-α, Bax, and active caspase-3, and decreased the expression of eNOS and Bcl2. Hyperglycaemia-like conditions also increased the indices of oxidative/nitrosative stress. These HG-induced changes, which were accompanied by an increase in tissue adventitial thickness and inflammatory cell infiltration, were all prevented by DHM.

Conclusion: Our data demonstrate an anti-inflammatory protective action of DHM to preserve vascular function in the setting of hyperglycaemia.

Keywords: Aortic rings; Dihydromyricetin; Endothelial dysfunction; HIF-1α; Hypoxia-inducible factor; In vitro hyperglycaemia; Inducible nitric oxide synthase; Oxidative stress; iNOS.