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

Abstract

<jats:p>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.</jats:p>

Acacetin Protects Against High Glucose-Induced Endothelial Cells Injury by Preserving Mitochondrial Function via Activating Sirt1/Sirt3/AMPK Signals

“…The therapeutic strategies to treat diabetic atherosclerosis include approaches to prevent, inhibit or reverse diabetic cardiovascular complications. Previous studies have demonstrated that endothelial protection using exogenous antioxidants to modulate the endothelium-dependent vasodilation responses, the homeostatic endothelium-leukocyte interactions, the balance between pro-and anti-thrombotic properties and/or the vascular apoptotic responses is effective in attenuating vascular disorders in diabetes mellitus (Pratico, 2005;Taile et al, 2020). Activation of eNOS is atheroprotective in diabetes (Sharma et al, 2015).…”

Hyperglycemic Condition Causes Pro-Inflammatory and Permeability Alterations Associated with Monocyte Recruitment and Deregulated NFκB/PPARγ Pathways on Cerebral Endothelial Cells: Evidence for Polyphenols Uptake and Protective Effect

“…The experimental hyperglycemia was mimicked by a high glucose concentration (33 mM) and conducted in a time-dependent manner from 3–24 h, given that it caused time-dependent oxidative stress and deregulation of vasoactive markers without affecting the viability of bEnd3 cells in our previous studies [ 20 , 26 ]. Four characterized polyphenol-rich extracts from the French medicinal plants A. borbonica , A. triplinervis , D. viscosa and T. bentzoe , and their predominant polyphenols quercetin, caffeic, chlorogenic and gallic acids were assessed, since we previously showed that they exhibited antioxidant properties on bEnd3 cells during hyperglycemic condition [ 21 ]. These polyphenolic plant extracts were prepared from the leaves which constitute the most traditionally collected plant compartments used for herbal remedies [ 27 ], despite the fact that here a pharmacological approach was achieved by using aqueous-acetonic extraction to enrich polyphenolic fractions [ 21 ].…”

“…Recently, we showed that polyphenols extracted from four medicinal plants referenced in the French Pharmacopeia for antidiabetic properties, namely Antirhea borbonica , Ayapana triplinervis , Dodonaea viscosa and Terminalia bentzoe , attenuate oxidative stress and the alteration of vasoactive markers production in cerebral endothelial cells during the hyperglycemic condition. Quercetin, caffeic, chlorogenic and gallic acids that we detected as major polyphenols in these medicinal plant extracts exhibit similar protective properties [ 20 , 21 ]. However, the impact of these polyphenolic plant extracts on the inflammatory response and permeability of cerebral endothelial cells remains poorly elucidated.…”

Protective Effects of Medicinal Plant Decoctions on Macrophages in the Context of Atherosclerosis

“…Medicinal plant decoctions traditionally used in Reunion Island could represent the basis of new therapeutic strategies aimed at preventing or limiting the progression of atherosclerosis [ 27 , 31 ]. Many medicinal plants from Reunion Island are rich in polyphenols, and their composition is described in our previous study [ 27 ].…”

“…Our previous study on eight medicinal plants used in Reunion Island revealed the presence of bioactive polyphenols (such as quercetin, gallic acid, mangiferin) and antioxidant properties on in vitro models (human red blood cells and murine preadipocytes 3T3-L1) [ 27 ]. Ethnopharmacological studies support the interest of medicinal plant antioxidant and anti-inflammatory activities in the management of different pathologies including atherosclerosis [ 28 , 29 , 30 , 31 ].…”