Natural therapeutic magnesium lithospermate B potently protects the endothelium from hyperglycaemia-induced dysfunction
Natural therapeutic magnesium lithospermate B potently protects the endothelium from hyperglycaemia-induced dysfunction
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DOI：
10.1093/cvr/cvq089
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发表时间：
2010-09-01
影响因子：
10.8
通讯作者：
Lee, Hyun Chul
中科院分区：
文献类型：
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作者：
Kim, So Hun;Kim, Soo Hyun;Lee, Hyun Chul
本研究采用培养内皮细胞和2型糖尿病动物模型，研究了中药丹参的活性成分石精酸镁B （MLB）对糖尿病相关内皮功能障碍的影响。观察MLB对大冢Long-Evans德岛脂肪（OLETF）大鼠血管舒张功能的影响。从12周开始，MLB治疗20周，可减轻OLETF大鼠内皮依赖性血管舒张的下降。MLB治疗还增加了血清亚硝酸盐水平，降低了血清晚期糖基化终产物浓度。MLB的效果大于等量的α -硫辛酸（α - LA），一种流行的抗氧化治疗。在高血糖培养的内皮细胞中，MLB恢复了内皮一氧化氮合酶（eNOS）活性和eNOS磷酸化的抑制。这种作用依赖于Akt磷酸化，并与eNOS O-linked n -乙酰氨基葡萄糖蛋白修饰减少有关。MLB还以磷酸化肌苷3-激酶/Akt通路依赖的方式增加核因子红系2相关因子-2 （Nrf-2）的激活。MLB处理诱导nrf -2调控的抗氧化酶血红素加氧酶-1的表达。抗氧化剂α - LA不能产生这种作用。此外，MLB还能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一代抗氧化剂，可激活eNOS，并通过增强血管舒张和减少氧化应激来改善糖尿病的内皮功能障碍。MLB相对较强的性能使其成为进一步扩大试验的理想候选者，作为新一代抗氧化剂治疗糖尿病相关并发症。
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 (alpha LA), 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 alpha LA 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.