Boldine protects endothelial function in hyperglycemia-induced oxidative stress through an antioxidant mechanism
Boldine protects endothelial function in hyperglycemia-induced oxidative stress through an antioxidant mechanism
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DOI：
10.1016/j.bcp.2012.11.010
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发表时间：
2013-02-01
影响因子：
5.8
通讯作者：
Mustafa, Mohd Rais
中科院分区：
文献类型：
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作者：
Lau, Yeh Siang;Tian, Xiao Yu;Mustafa, Mohd Rais
氧化应激增加参与糖尿病的发病机制和进展。抗氧化剂对于氧化应激相关疾病有治疗作用。 Boldine ([s]-2,9-二羟基-1,10-二甲氧基阿朴啡) 是一种存在于博尔多树 (Peumus Boldus Molina) 叶子和树皮中的主要生物碱，具有已知的抗氧化活性。本研究探讨了博尔丁对高糖诱导的大鼠主动脉内皮细胞（RAEC）氧化应激的保护作用及其与糖尿病内皮功能障碍相关的血管保护机制。在暴露于高葡萄糖 (30 mM) 48 小时的 RAEC 中，用 Bolline 预处理可减少升高的 ROS 和硝基酪氨酸形成，并保留一氧化氮 (NO) 的产生。与 β-NAPDH 预孵育可减少乙酰胆碱诱导的内皮依赖性舒张；博尔丁逆转了这种衰减。与对照相比，链脲佐菌素（STZ）治疗的糖尿病大鼠的主动脉内皮依赖性松弛通过博尔丁的急性（1μM，30分钟）和慢性（20mg/kg/每日，腹膜内注射，7天）治疗均得到显着改善。通过 DHE 荧光或化学发光测定法测得的糖尿病大鼠主动脉环切片中细胞内超氧化物和过氧亚硝酸盐的形成量高于对照组。长期的Boldine治疗使糖尿病组中ROS过度产生正常化，这与NAD(P)H氧化酶亚基、NOX2和p47(phox)的减少相关。本研究表明，Boldine逆转了高葡萄糖处理的内皮细胞中ROS形成的增加，并通过抑制氧化应激从而增加NO生物利用度来恢复STZ诱导的糖尿病中的内皮功能。 (C) 2012 Elsevier Inc. 保留所有权利。
Increased oxidative stress is involved in the pathogenesis and progression of diabetes. Antioxidants are therapeutically beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1,10-dimethoxyaporphine) is a major alkaloid present in the leaves and bark of the boldo tree (Peumus boldus Molina), with known an antioxidant activity. This study examined the protective effects of boldine against high glucose-induced oxidative stress in rat aortic endothelial cells (RAEC) and its mechanisms of vasoprotection related to diabetic endothelial dysfunction. In RAEC exposed to high glucose (30 mM) for 48 h, pre-treatment with boldine reduced the elevated ROS and nitrotyrosine formation, and preserved nitric oxide (NO) production. Pre-incubation with beta-NAPDH reduced the acetylcholine-induced endothelium-dependent relaxation; this attenuation was reversed by boldine. Compared with control, endothelium-dependent relaxation in the aortas of streptozotocin (STZ)-treated diabetic rats was significantly improved by both acute (1 mu M, 30 min) and chronic (20 mg/kg/daily, i.p., 7 days) treatment with boldine. Intracellular superoxide and peroxynitrite formation measured by DHE fluorescence or chemiluminescence assay were higher in sections of aortic rings from diabetic rats compared with control. Chronic boldine treatment normalized ROS over-production in the diabetic group and this correlated with reduction of NAD(P)H oxidase subunits, NOX2 and p47(phox) The present study shows that boldine reversed the increased ROS formation in high glucose-treated endothelial cells and restored endothelial function in STZ-induced diabetes by inhibiting oxidative stress and thus increasing NO bioavailability. (C) 2012 Elsevier Inc. All rights reserved.