ABSTRACT Gastrodin (GAS) is a predominant bioactive constituent of the Chinese herbal medicine Tianma (Gastrodia elata Blume). Many authors have reported GAS has the beneficial effect on diverse diseases of the CNS, including epilepsy, Alzheimer’s disease, Parkinson’s disease, and cerebral ischemia. Here, we report GAS exhibited a robust neuroprotective effect in an Sprague-Dawley rat model of stroke (transient middle cerebral artery occlusion, tMCAO), and show that the underlying molecular mechanism involves its protective effect against Zn2+-toxicity and its anti-oxidative effects in astrocytes. Intraperitoneal administration of GAS (40 mg/kg) after MCAO reduced mean infarct volume to 30.1 ± 5.9% of that of MCAO controls and this neuroprotective effect was accompanied by neurological function recoveries which was measured using modified neurological severity score (mNSS). Interestingly, GAS induced up-regulation and nuclear translocation of Nrf2, and subsequently increased the expressions of anti-oxidative genes, such as, HO-1 and GCLM, in astrocytes. Furthermore, GAS co- or pre-treatment markedly suppressed Zn2+-induced cell death caused by excessive ROS production and PARP-1 induction. We found that GAS suppressed p67 expression and PAR formation in astrocytes, which might underlie the anti- Zn2+-toxicity and anti-oxidative effects of GAS in astrocytes. These findings indicate GAS protects astrocytes from Zn2+-induced toxicity and oxidative stress and these effects contribute to its neuroprotective effects in the postischemic brain.

中文翻译：

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天麻素通过其对 Zn2+ 毒性的保护作用及其在星形胶质细胞中的抗氧化作用在缺血后脑中发挥强大的神经保护作用

摘要 天麻素 (GAS) 是中草药天麻 (Gastrodia elata Blume) 的主要生物活性成分。许多作者报道 GAS 对多种中枢神经系统疾病具有有益作用，包括癫痫、阿尔茨海默病、帕金森病和脑缺血。在这里，我们报告 GAS 在 Sprague-Dawley 大鼠中风模型（暂时性大脑中动脉闭塞，tMCAO）中表现出强大的神经保护作用，并表明潜在的分子机制涉及其对 Zn2+ 毒性的保护作用及其抗氧化作用在星形胶质细胞中。MCAO 后腹腔注射 GAS (40 mg/kg) 将平均梗塞体积降低至 30.1 ± 5。MCAO 对照的 9%，这种神经保护作用伴随着神经功能恢复，使用修正的神经严重程度评分 (mNSS) 进行测量。有趣的是，GAS 诱导 Nrf2 的上调和核易位，随后增加了星形胶质细胞中抗氧化基因（如 HO-1 和 GCLM）的表达。此外，GAS 联合或预处理显着抑制了由过量 ROS 产生和 PARP-1 诱导引起的 Zn2+ 诱导的细胞死亡。我们发现 GAS 抑制了星形胶质细胞中 p67 的表达和 PAR 的形成，这可能是 GAS 在星形胶质细胞中的抗 Zn2+ 毒性和抗氧化作用的基础。这些发现表明 GAS 保护星形胶质细胞免受 Zn2+ 诱导的毒性和氧化应激，这些作用有助于其在缺血后脑中的神经保护作用。