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

Wuyang Huang,Wuyang Huang,Zhi Chai,Tiesong Zheng,Ruth Paulina Hutabarat,Weimin Zhang,Dajing Li,Ruth Paulina Hutabarat

doi:10.3390/ijms21051575

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.

Highlights

Cardiovascular disease (CVD) is the leading cause of death in the world, with 80–90% of cardiovascular disease patients having hypertension [1]
AndyGene human superoxide dismutase (SOD), xanthine oxidase-1 (XO-1), heme oxygenase-1 (HO-1), low-density lipoprotein (LDL), nitric oxide (NO), endothelial nitric oxide synthase, and angiotensin-converting enzyme (ACE) enzyme-linked immunosorbent assay (ELISA) kits were purchased from Shanghai Bluegene Biotech (Shanghai, China)
Blueberry anthocyanin extract as well as the major constituent malvidin and its derivatives Mv-3-glc, Mv-3-gal have been proved in this study as a potential hypotensive nutraceutical that could efficaciously ameliorate endothelial functions and improve vascular health in this study

Summary

Introduction

Cardiovascular disease (CVD) is the leading cause of death in the world, with 80–90% of cardiovascular disease patients having hypertension [1]. The World Health Organization estimated that 17.6 million people died from cardiovascular disease in 2016, representing 44% of all global deaths. Diabetes is a typical risk factor that promotes cardiovascular diseases, especially hypertension [2]. According to the American Diabetes Association reports from 1999 to 2012, 71% of type 2 diabetes mellitus adult patients had hypertension [3]. Hyperglycemia is known to be the main contributing factor in the progression of the disease, which triggers pathological metabolic and biochemical changes that damage the cells [4]. Diabetes may increase blood pressure by reducing the blood vessels’

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