Antioxidant Blueberry Anthocyanins Induce Vasodilation via PI3K/Akt Signaling Pathway in High-Glucose-Induced Human Umbilical Vein Endothelial Cells

Abstract

Blueberries are rich in antioxidant anthocyanins. The hypotensive effects of blueberry anthocyanins in endothelial cells was investigated here. Pretreatment with blueberry anthocyanin extract, malvidin, malvidin-3-glucoside, and malvidin-3-galactoside significantly ameliorated high-glucose-induced damage by enhancing endogenous antioxidant superoxide dismutase (SOD) and heme oxygenase-1 (HO-1), lowering reactive oxygen species (ROS) generation and NADPH oxidase isoform 4 (NOX4) expression, and increasing the cell vitalities. They also effectively induced a vasodilatory effect by increasing the vasodilator nitric oxide (NO) and its promoters endothelial NO synthase (eNOS) and peroxisome proliferator-activated receptor-γ (PPARγ) levels as well as by decreasing the vasoconstrictor angiotensin-converting enzyme (ACE), xanthine oxidase-1 (XO-1), and low-density lipoprotein (LDL) levels. The activation of phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and the breakdown of protein kinase C zeta (PKCζ) pathway were involved in the bioactivities. The results indicated blueberry anthocyanins protected endothelial function against high-glucose (HG) injury via antioxidant and vasodilatory mechanisms, which could be promising molecules as a hypotensive nutraceutical for diabetes patients.

Vaccinium Species (Ericaceae): From Chemical Composition to Bio-Functional Activities

“…In similar models, this compound also reduces vascular endothelial growth factor (VEGF) up-regulation, ICAM-1 expression, and NF-κB (p65) levels [112]. In addition, malvidin has been shown to be able to restore PI3K and Akt levels, which are reduced by high glucose [113].…”

Going “Green” in the Prevention and Management of Atherothrombotic Diseases: The Role of Dietary Polyphenols

“…NO produced from L-arginine in a reaction catalyzed by the nitric oxide synthase (NOS) is a known vasodilator that contributes to endothelial function. Flavonoids have been reported to potentiate vascular function by the activation of endothelial NO synthase [ 162 , 165 , 166 ] as well as by preserving the integrity of tight junctions and promoting the expression of tight-junction proteins even under inflammatory conditions averting the expression of claudin-2 by inflammatory cytokines [ 167 ]. Álvarez-Cilleros found that gut microbial flavanol metabolites increased NO production in human endothelial cells (EA.hy927) after the treatment with 10 µM of 3,4-DHPA or with a mix of that metabolite with 2,3-dihydroxybenzoic acid (2,3-DHB) and 3-hydroxyphenylpropionic acid (3-HPPA) [ 34 ].…”

The Emerging Roles of Antioxidant Enzymes by Dietary Phytochemicals in Vascular Diseases

“…Another study showed that anthocyanins could ameliorate human retinal capillary endothelial function by decreasing ROS and increasing the enzyme activity of CAT and SOD and, therefore, might have the potential to avert the progression of diabetic retinopathy [ 72 ]. A recent study indicated that anthocyanins protected rodent endothelial function against high-glucose injury through antioxidant and vasodilatory mechanisms, so anthocyanins could be a promising hypotensive nutraceutical for diabetes [ 73 ].…”