Neuroprotective Effect Of Danshensu Derivatives As Anti- Ischemia Agents On SH-SY5Y Neuronal Cell And Rat Brain

Neuroprotective effects of novel Danshensu derivatives (3-8) which were designed and synthesized to improve bioactivity based on the strategy of "medicinal chemical hybridization", were reported in this paper. These conjugated compounds exhibited noticeable neuroprotective activities on hypoxia induced cell damage in human neuroblastoma cells (SH-SY5Y). In vitro study revealed that all these compounds could increase cell viability and reduce LDH leakage. Moreover, Danshensu-cysteine derivative6 and 8could significantly inhibit lipid peroxidation of cell membrane and regulate the expression of apoptosis-related protein (bcl-2, bax and caspase 3). The compounds up-regulate the expression bcl-2 and down-regulate bax and caspase 3. In vivo study demonstrated that compound 6 at 30 mg/kg markedly decrease the infarct volume. Furthermore, compound 6 showed the antioxidant activity by increasing the activity of SOD and GPx and decreasing level of MDA and the ROS production significantly. These results suggested that these novel conjugates exert significant neuroprotective effects as an anti-ischemia and those with high potential merit further investigation.