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药用植物的抗氧化多酚和咖啡酸可减轻高脂饮食诱导肥胖的小鼠中风模型中加重的脑血管、炎症和代谢紊乱。

Antioxidant Polyphenols of Medicinal Plant and Caffeic Acid Reduce Cerebrovascular, Inflammatory and Metabolic Disorders Aggravated by High-Fat Diet-Induced Obesity in a Mouse Model of Stroke.

作者信息

Taïlé Janice, Bringart Matthieu, Planesse Cynthia, Patché Jessica, Rondeau Philippe, Veeren Bryan, Clerc Patricia, Gauvin-Bialecki Anne, Bourane Steeve, Meilhac Olivier, Couret David, Gonthier Marie-Paule

机构信息

Université de La Réunion, INSERM, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), 97490 Sainte-Clotilde, La Réunion, France.

UR 2212 Laboratoire de Chimie et de Biotechnologie des Produits Naturels (ChemBioPro), Université de La Réunion, CEDEX 9, 97744 Saint-Denis, La Réunion, France.

出版信息

Antioxidants (Basel). 2022 Apr 27;11(5):858. doi: 10.3390/antiox11050858.

DOI:10.3390/antiox11050858
PMID:35624723
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9138119/
Abstract

Metabolic disorders related to obesity and type 2 diabetes are associated with aggravated cerebrovascular damages during stroke. In particular, hyperglycemia alters redox and inflammatory status, leading to cerebral endothelial cell dysfunction, blood-brain barrier (BBB) disruption and brain homeostasis loss. Polyphenols constitute the most abundant dietary antioxidants and exert anti-inflammatory effects that may improve cerebrovascular complications in stroke. This study evaluated the effects of the characterized polyphenol-rich extract of medicinal plant and its major constituent caffeic acid on a high-fat diet (HFD)-induced obesity mouse model during ischemic stroke, and murine bEnd3 cerebral endothelial cells in high glucose condition. In vivo, polyphenols administered by oral gavage for 12 weeks attenuated insulin resistance, hyperglycemia, hyperinsulinemia and dyslipidemia caused by HFD-induced obesity. Polyphenols limited brain infarct, hemorrhagic transformation and BBB disruption aggravated by obesity during stroke. Polyphenols exhibited anti-inflammatory and antioxidant properties by reducing IL-1β, IL-6, MCP-1, TNF-α and Nrf2 overproduction as well as total SOD activity elevation at the cerebral or peripheral levels in obese mice. In vitro, polyphenols decreased MMP-2 activity that correlated with MCP-1 secretion and ROS intracellular levels in hyperglycemic condition. Protective effects of polyphenols were linked to their bioavailability with evidence for circulating metabolites including caffeic acid, quercetin and hippuric acid. Altogether, these findings show that antioxidant polyphenols reduced cerebrovascular, inflammatory and metabolic disorders aggravated by obesity in a mouse model of stroke. It will be relevant to assess polyphenol-based strategies to improve the clinical consequences of stroke in the context of obesity and diabetes.

摘要

与肥胖和2型糖尿病相关的代谢紊乱与中风期间脑血管损伤加重有关。特别是，高血糖会改变氧化还原和炎症状态，导致脑内皮细胞功能障碍、血脑屏障（BBB）破坏和脑稳态丧失。多酚是饮食中最丰富的抗氧化剂，具有抗炎作用，可能改善中风时的脑血管并发症。本研究评估了药用植物中富含特征性多酚的提取物及其主要成分咖啡酸对缺血性中风期间高脂饮食（HFD）诱导的肥胖小鼠模型以及高糖条件下小鼠bEnd3脑内皮细胞的影响。在体内，通过口服灌胃给予多酚12周可减轻HFD诱导的肥胖所导致的胰岛素抵抗、高血糖、高胰岛素血症和血脂异常。多酚可限制中风期间因肥胖而加重的脑梗死、出血性转化和BBB破坏。多酚通过降低肥胖小鼠大脑或外周水平的IL-1β、IL-6、MCP-1、TNF-α和Nrf2的过量产生以及总SOD活性升高，表现出抗炎和抗氧化特性。在体外，多酚可降低MMP-2活性，这与高糖条件下MCP-1分泌和细胞内ROS水平相关。多酚的保护作用与其生物利用度有关，有证据表明包括咖啡酸、槲皮素和马尿酸在内的循环代谢物存在。总之，这些发现表明抗氧化多酚可减轻中风小鼠模型中因肥胖而加重的脑血管、炎症和代谢紊乱。评估基于多酚的策略以改善肥胖和糖尿病背景下中风的临床后果将具有重要意义。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c87/9138119/0f9ac677add5/antioxidants-11-00858-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c87/9138119/3834da7859de/antioxidants-11-00858-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c87/9138119/49e4c6c4c4d3/antioxidants-11-00858-g005.jpg
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