Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea.
Cardiovasc Res. 2010 Sep 1;87(4):713-22. doi: 10.1093/cvr/cvq089. Epub 2010 Mar 17.
We have investigated the effects of magnesium lithospermate B (MLB), the active compound of the Oriental herbal remedy, Salvia miltiorrhizae, on endothelial dysfunction associated with diabetes mellitus using cultured endothelial cells and an animal model of type 2 diabetes mellitus.
The effect of MLB on vasodilatory function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats was assessed. MLB treatment for 20 weeks starting at 12 weeks attenuated the decrease in endothelium-dependent vasodilation in OLETF rats. MLB treatment also increased serum nitrite level and reduced serum advanced glycation end products concentration. The effect of MLB was greater than an equivalent dose of alpha-lipoic acid (alphaLA), a popular antioxidant treatment. MLB rescued the inhibition of endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation in endothelial cells cultured in hyperglycaemia. This effect was dependent on Akt phosphorylation and associated with decreased O-linked N-acetylglucosamine protein modification of eNOS. MLB also increased nuclear factor erythroid 2-related factor-2 (Nrf-2) activation in a phosphoinositide 3-kinase/Akt pathway dependent manner. MLB treatment induced the expression of the Nrf-2-regulated antioxidant enzyme, heme oxygenase-1. The antioxidant alphaLA could not produce this effect. Moreover, MLB decreased oxidative stress and endothelial cell apoptosis caused by hyperglycaemia.
MLB is a naturally occurring, new generation antioxidant that activates eNOS and ameliorates endothelial dysfunction in diabetes by enhancing vasodilation in addition to reducing oxidative stress. The relative strong performance of MLB makes it an ideal candidate for further, expanded trials as a new generation of antioxidant to treat diabetes-related complications.
我们研究了丹参活性成分迷迭香酸镁（MLB）对糖尿病相关内皮功能障碍的影响，使用培养的内皮细胞和 2 型糖尿病动物模型。
评估 MLB 对 Otsuka Long-Evans Tokushima Fatty（OLETF）大鼠血管舒张功能的影响。从 12 周开始，20 周的 MLB 治疗可减轻 OLETF 大鼠内皮依赖性血管舒张功能的下降。MLB 治疗还增加了血清亚硝酸盐水平并降低了血清晚期糖基化终产物浓度。MLB 的作用大于等效剂量的α-硫辛酸（αLA），一种流行的抗氧化治疗。MLB 挽救了高血糖培养的内皮细胞中内皮型一氧化氮合酶（eNOS）活性和 eNOS 磷酸化的抑制作用。这种作用依赖于 Akt 磷酸化，并与 eNOS 的 O-连接 N-乙酰氨基葡萄糖蛋白修饰减少有关。MLB 还通过磷酸肌醇 3-激酶/Akt 途径依赖性方式增加核因子红细胞 2 相关因子 2（Nrf-2）的激活。MLB 治疗诱导 Nrf-2 调节的抗氧化酶血红素加氧酶-1 的表达。抗氧化剂 αLA 不能产生这种作用。此外，MLB 可降低高血糖引起的氧化应激和内皮细胞凋亡。
MLB 是一种天然存在的新型抗氧化剂，可通过增强血管舒张以及减轻氧化应激来激活 eNOS 并改善糖尿病中的内皮功能障碍。MLB 的相对较强性能使其成为治疗糖尿病相关并发症的新一代抗氧化剂的进一步扩展试验的理想候选药物。
