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

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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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