Neuroprotective effect of Danshensu derivatives as anti-ischaemia agents on SH-SY5Y cells and rat brain.
Neuroprotective effect of Danshensu derivatives as anti-ischaemia agents on SH-SY5Y cells and rat brain.
复制标题
丹参素衍生物作为抗缺血剂对SH-SY5Y细胞和大鼠脑的神经保护作用
DOI：
10.1042/bsr20130032
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发表时间：
2013-08-30
影响因子：
4
通讯作者：
Zhu YZ
中科院分区：
文献类型：
--
作者：
Seetapun S;Yaoling J;Wang Y;Zhu YZ
基于“药物化学杂交”策略，设计合成了新的丹参素衍生物（3-8），以提高其生物活性。我们之前的研究表明，这些化合物具有明显的心脏保护活性。在这里，我们研究这些新的丹参素衍生物是否具有神经保护作用。一项体外研究表明，这些化合物可以提高细胞活力，减少乳酸脱氢酶（LDH）泄漏。丹参素-半胱氨酸衍生物化合物6和8能显著抑制细胞膜脂质过氧化，调节凋亡相关蛋白（Bcl-2、Bax和caspase 3）的表达。一项体内研究表明，化合物6以30 mg/kg的剂量治疗可显著降低MCAO（大脑中动脉闭塞）损伤的大鼠脑梗死体积。此外，化合物6通过显著提高超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）活性，降低丙二醛（MDA）和活性氧（ROS）生成水平，显示出抗氧化能力。这些结果表明，这些新型缀合物作为抗缺血药物具有显著的神经保护作用，具有较高的潜力，值得进一步研究。
Novel Danshensu derivatives (3–8) were designed and synthesized to improve bioactivity based on the strategy of ‘medicinal chemical hybridization’. Our previous studies indicated that these compounds exhibited noticeable cardioprotective activities. Here, we investigate whether these novel Danshensu derivatives exert neuroprotective activities. An in vitro study revealed that these compounds could increase cell viability and reduce LDH (lactate dehydrogenase) leakage. Moreover, Danshensu-cysteine derivative compounds 6 and 8 could significantly inhibit lipid peroxidation of cell membrane and regulate the expression of apoptosis-related protein (Bcl-2, Bax and caspase 3). An in vivo study demonstrated that treatment with compound 6 at 30 mg/kg markedly decreased the infarct volume of MCAO (middle cerebral artery occlusion) insulted rat brain. Furthermore, treatment with compound 6 showed the antioxidant capacity by increasing the activity of SOD (superoxide dismutase) and GPx (glutathione peroxidase) and decreasing the level of MDA (malondialdehyde) and the ROS (reactive oxygen species) production significantly. These results suggested that these novel conjugates exert significant neuroprotective effects as anti-ischaemia agents and those with high potential merit further investigation.