Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, People's Republic of China.
Biosci Rep. 2013 Aug 30;33(4):e00062. doi: 10.1042/BSR20130032.
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.
新型丹参素衍生物（3-8）是基于“药物化学杂交”策略设计和合成的，旨在提高生物活性。我们之前的研究表明，这些化合物表现出显著的心脏保护活性。在这里，我们研究这些新型丹参素衍生物是否具有神经保护活性。体外研究表明，这些化合物可以提高细胞活力并减少 LDH（乳酸脱氢酶）渗漏。此外，丹参素半胱氨酸衍生物化合物 6 和 8 可以显著抑制细胞膜脂质过氧化，并调节凋亡相关蛋白（Bcl-2、Bax 和 caspase 3）的表达。体内研究表明，化合物 6 在 30mg/kg 剂量下治疗可显著减少大脑中动脉闭塞（MCAO）损伤大鼠的梗死体积。此外，化合物 6 通过增加 SOD（超氧化物歧化酶）和 GPx（谷胱甘肽过氧化物酶）的活性以及显著降低 MDA（丙二醛）和 ROS（活性氧）的水平，表现出抗氧化能力。这些结果表明，这些新型缀合物作为抗缺血剂具有显著的神经保护作用，具有高潜力值得进一步研究。
