Medicinal Plant Polyphenols Attenuate Oxidative Stress and Improve Inflammatory and Vasoactive Markers in Cerebral Endothelial Cells during Hyperglycemic Condition.

Janice Taïlé,Anne Gauvin-Bialecki,Patricia Clerc,Angélique Arcambal,Marie-Paule Gonthier

doi:10.3390/antiox9070573

Janice Taïlé, Anne Gauvin-Bialecki + Show 3 more

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https://doi.org/10.3390/antiox9070573

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Abstract

Blood-brain barrier endothelial cells are the main targets of diabetes-related hyperglycemia that alters endothelial functions and brain homeostasis. Hyperglycemia-mediated oxidative stress may play a causal role. This study evaluated the protective effects of characterized polyphenol-rich medicinal plant extracts on redox, inflammatory and vasoactive markers on murine bEnd3 cerebral endothelial cells exposed to high glucose concentration. The results show that hyperglycemic condition promoted oxidative stress through increased reactive oxygen species (ROS) levels, deregulated antioxidant superoxide dismutase (SOD) activity, and altered expression of genes encoding Cu/ZnSOD, MnSOD, catalase, glutathione peroxidase (GPx), heme oxygenase-1 (HO-1), NADPH oxidase 4 (Nox4), and nuclear factor erythroid 2-related factor 2 (Nrf2) redox factors. Cell preconditioning with inhibitors of signaling pathways highlights a causal role of nuclear factor kappa B (NFκB), while a protective action of AMP-activated protein kinase (AMPK) on redox changes. The hyperglycemic condition induced a pro-inflammatory response by elevating NFκB gene expression and interleukin-6 (IL-6) secretion, and deregulated the production of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), and nitric oxide (NO) vasoactive markers. Importantly, polyphenolic extracts from Antirhea borbonica, Ayapana triplinervis, Dodonaea viscosa, and Terminalia bentzoe French medicinal plants, counteracted high glucose deleterious effects by exhibiting antioxidant and anti-inflammatory properties. In an innovative way, quercetin, caffeic, chlorogenic and gallic acids identified as predominant plant polyphenols, and six related circulating metabolites were found to exert similar benefits. Collectively, these findings demonstrate polyphenol protective action on cerebral endothelial cells during hyperglycemic condition.

Highlights

The blood-brain barrier (BBB) is composed of microvascular endothelial cells that correspond to a monolayer of flat cells lining the interior surface of blood vessels
Oxidative stress is defined as an imbalance between the production of reactive oxygen species (ROS) and the rate of their degradation by the endogenous antioxidant defense system, which is composed of various enzymes, such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1) [12]
The present study aimed to evaluate the protective effects of characterized polyphenol-rich extracts from medicinal plants on redox, inflammatory, and vasoactive markers of cerebral endothelial cells that were exposed to hyperglycemic condition

Summary

Introduction

The blood-brain barrier (BBB) is composed of microvascular endothelial cells that correspond to a monolayer of flat cells lining the interior surface of blood vessels. These endothelial cells exert important physiological functions in order to maintain the cerebral microenvironment and Antioxidants 2020, 9, 573; doi:10.3390/antiox9070573 www.mdpi.com/journal/antioxidants. Endothelial cells produce a wide range of factors comprising vasodilators, like nitric oxide (NO) produced by the endothelial nitric oxide synthase (eNOS), and vasoconstrictors, including endothelin-1 (ET-1) [3,4]. Oxidative stress is defined as an imbalance between the production of reactive oxygen species (ROS) and the rate of their degradation by the endogenous antioxidant defense system, which is composed of various enzymes, such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and heme oxygenase-1

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