Diabète athérothrombose Thérapies Réunion Océan Indien, INSERM, UMR 1188, Université de La Réunion, 2 rue Maxime Rivière, 97490 Sainte-Clotilde, La Réunion, France.
Int J Mol Sci. 2021 Jan 30;22(3):1385. doi: 10.3390/ijms22031385.
Hyperglycemia alters the function of cerebral endothelial cells from the blood-brain barrier, increasing the risk of cerebrovascular complications during diabetes. This study evaluated the protective effect of polyphenols on inflammatory and permeability markers on bEnd3 cerebral endothelial cells exposed to high glucose concentration. Results show that hyperglycemic condition increased nuclear factor kappa B (NFκB) activity, deregulated the expression of interleukin-1 beta (), interleukin-6 (), tumor necrosis factor-alpha (), cyclooxygenase-2 (), inducible nitric oxide synthase (), interleukin-10 () and endothelial-leukocyte adhesion molecule () genes, raised MCP-1 secretion and elevated monocyte adhesion and transendothelial migration. High glucose decreased occludin, claudin-5, zona occludens-1 (ZO-1) and zona occludens-2 (ZO-2) tight junctions production and altered the endothelial permeability. Characterized polyphenolic extracts from the French medicinal plants , , and , and their major polyphenols quercetin, caffeic, chlorogenic and gallic acids limited the pro-inflammatory and permeability alterations caused by high glucose. Peroxisome proliferator-activated receptor gamma (PPARγ) agonist also attenuated these damages while PPARγ antagonist aggravated them, suggesting PPARγ protective action. Interestingly, polyphenols improved gene expression lowered by high glucose. Moreover, polyphenols were detected at the intracellular level or membrane-bound to cells, with evidence for breast cancer resistance protein (BCRP) efflux transporter role. Altogether, these findings emphasize the ability of polyphenols to protect cerebral endothelial cells in hyperglycemic condition and their relevance for pharmacological strategies aiming to limit cerebrovascular disorders in diabetes.
高血糖会改变血脑屏障中脑内皮细胞的功能，增加糖尿病期间脑血管并发症的风险。本研究评估了多酚对暴露于高葡萄糖浓度下的 bEnd3 脑内皮细胞的炎症和通透性标志物的保护作用。结果表明，高血糖状态增加了核因子 kappa B（NFκB）的活性，使白细胞介素-1β（）、白细胞介素-6（）、肿瘤坏死因子-α（）、环氧化酶-2（）、诱导型一氧化氮合酶（）、白细胞介素-10（）和内皮白细胞黏附分子（）基因的表达失调，增加单核细胞趋化蛋白-1（MCP-1）的分泌，并增加单核细胞黏附和跨内皮迁移。高葡萄糖降低了紧密连接蛋白 occludin、claudin-5、zonula occludens-1（ZO-1）和 zonula occludens-2（ZO-2）的产生，并改变了内皮通透性。法国药用植物、、和的特征性多酚提取物及其主要多酚槲皮素、咖啡酸、绿原酸和没食子酸，限制了高葡萄糖引起的促炎和通透性改变。过氧化物酶体增殖物激活受体 γ（PPARγ）激动剂也减轻了这些损伤，而 PPARγ 拮抗剂则加重了这些损伤，表明 PPARγ 具有保护作用。有趣的是，多酚改善了高葡萄糖降低的基因表达。此外，多酚在细胞内水平或细胞膜结合到细胞上被检测到，这表明乳腺癌耐药蛋白（BCRP）外排转运体的作用。总之，这些发现强调了多酚在高血糖状态下保护脑内皮细胞的能力，以及它们在旨在限制糖尿病中脑血管疾病的药理学策略中的相关性。
