Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, People's Republic of China,
J Mol Neurosci. 2013 Oct;51(2):550-7. doi: 10.1007/s12031-013-0023-7. Epub 2013 May 3.
Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae (Dan Shen), which is a Chinese traditional herbal medicine with therapeutic effects on cardiovascular and cerebrovascular diseases. The aim of this study was to investigate the neuroprotective effects of MLB on N-methyl-D-aspartic acid (NMDA)-injured neurons and against kainic acid (KA)-induced neurodegeneration in mice. In cultured mouse primary hippocampal neurons, MLB significantly reduced NMDA-induced cell death and promoted neurite growth in a dose-dependent manner. In FVB mice, MLB attenuated KA-induced neurodegeneration. Additionally, MLB prevented the decrease in phosphorylated Akt and glycogen synthase kinase-3β (GSK-3β) levels both in NMDA-injured neurons and KA-injured mouse brain. This effect was blocked by phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and Akt inhibitor triciribine, thus indicating the neuroprotective effects of MLB are most likely mediated by the PI3K/Akt/GSK-3β pathway. Taken together, these results show the efficacy and underlying mechanism of MLB against neuronal injury and raise its therapeutic potential in neurodegenerative diseases.
丹参中的主要生物活性成分之一是丹参素镁（MLB），这是一种具有治疗心血管和脑血管疾病功效的中药。本研究旨在探讨 MLB 对 N-甲基-D-天冬氨酸（NMDA）损伤神经元的神经保护作用，以及对小鼠红藻氨酸（KA）诱导的神经退行性变的作用。在培养的小鼠原代海马神经元中，MLB 显著降低 NMDA 诱导的细胞死亡，并呈剂量依赖性促进神经突生长。在 FVB 小鼠中，MLB 减轻 KA 诱导的神经退行性变。此外，MLB 可防止 NMDA 损伤神经元和 KA 损伤小鼠大脑中磷酸化 Akt 和糖原合成酶激酶-3β（GSK-3β）水平的降低。该作用可被磷脂酰肌醇 3-激酶（PI3K）抑制剂 LY294002 和 Akt 抑制剂曲昔派特阻断，表明 MLB 的神经保护作用可能是通过 PI3K/Akt/GSK-3β 途径介导的。综上所述，这些结果表明 MLB 对抗神经元损伤的功效和潜在机制，并提高了其在神经退行性疾病中的治疗潜力。
